Changes in rapid HIV treatment initiation after national "treat all" policy adoption in 6 sub-Saharan African countries: Regression discontinuity analysis.
Most countries have formally adopted the World Health Organization's 2015 recommendation of universal HIV treatment ("treat all"). However, there are few rigorous assessments of the real-world impact of treat all policies on antiretroviral treatment (ART) uptake across different contexts. We used longitudinal data for 814,603 patients enrolling in HIV care between 1 January 2004 and 10 July 2018 in 6 countries participating in the global International epidemiology Databases to Evaluate AIDS (IeDEA) consortium: Burundi (N = 11,176), Kenya (N = 179,941), Malawi (N = 84,558), Rwanda (N = 17,396), Uganda (N = 96,286), and Zambia (N = 425,246). Using a quasi-experimental regression discontinuity design, we assessed the change in the proportion initiating ART within 30 days of enrollment in HIV care (rapid ART initiation) after country-level adoption of the treat all policy. A modified Poisson model was used to identify factors associated with failure to initiate ART rapidly under treat all. In each of the 6 countries, over 60% of included patients were female, and median age at enrollment ranged from 32 to 36 years. In all countries studied, national adoption of treat all was associated with large increases in rapid ART initiation. Significant increases in rapid ART initiation immediately after treat all policy adoption were observed in Rwanda, from 44.4% to 78.9% of patients (34.5 percentage points [pp], 95% CI 27.2 to 41.7; p < 0.001), Kenya (25.7 pp, 95% CI 21.8 to 29.5; p < 0.001), Burundi (17.7 pp, 95% CI 6.5 to 28.9; p = 0.002), and Malawi (12.5 pp, 95% CI 7.5 to 17.5; p < 0.001), while no immediate increase was observed in Zambia (0.4 pp, 95% CI -2.9 to 3.8; p = 0.804) and Uganda (-4.2 pp, 95% CI -9.0 to 0.7; p = 0.090). The rate of rapid ART initiation accelerated sharply following treat all policy adoption in Malawi, Uganda, and Zambia; slowed in Kenya; and did not change in Rwanda and Burundi. In post hoc analyses restricted to patients enrolling under treat all, young adults (16-24 years) and men were at increased risk of not rapidly initiating ART (compared to older patients and women, respectively). However, rapid ART initiation following enrollment increased for all groups as more time elapsed since treat all policy adoption. Study limitations include incomplete data on potential ART eligibility criteria, such as clinical status, pregnancy, and enrollment CD4 count, which precluded the assessment of rapid ART initiation specifically among patients known to be eligible for ART before treat all. Our analysis indicates that adoption of treat all policies had a strong effect on increasing rates of rapid ART initiation, and that these increases followed different trajectories across the 6 countries. Young adults and men still require additional attention to further improve rapid ART initiation.


In silico prediction of the mechanobiological response of arterial tissue: application to angioplasty and stenting.
One way to restore physiological blood flow to occluded arteries involves the deformation of plaque using an intravascular balloon and preventing elastic recoil using a stent. Angioplasty and stent implantation cause unphysiological loading of the arterial tissue, which may lead to tissue in-growth and reblockage; termed "restenosis." In this paper, a computational methodology for predicting the time-course of restenosis is presented. Stress-induced damage, computed using a remaining life approach, stimulates inflammation (production of matrix degrading factors and growth stimuli). This, in turn, induces a change in smooth muscle cell phenotype from contractile (as exists in the quiescent tissue) to synthetic (as exists in the growing tissue). In this paper, smooth muscle cell activity (migration, proliferation, and differentiation) is simulated in a lattice using a stochastic approach to model individual cell activity. The inflammation equations are examined under simplified loading cases. The mechanobiological parameters of the model were estimated by calibrating the model response to the results of a balloon angioplasty study in humans. The simulation method was then used to simulate restenosis in a two dimensional model of a stented artery. Cell activity predictions were similar to those observed during neointimal hyperplasia, culminating in the growth of restenosis. Similar to experiment, the amount of neointima produced increased with the degree of expansion of the stent, and this relationship was found to be highly dependant on the prescribed inflammatory response. It was found that the duration of inflammation affected the amount of restenosis produced, and that this effect was most pronounced with large stent expansions. In conclusion, the paper shows that the arterial tissue response to mechanical stimulation can be predicted using a stochastic cell modeling approach, and that the simulation captures features of restenosis development observed with real stents. The modeling approach is proposed for application in three dimensional models of cardiovascular stenting procedures.


Two tumor promoters, 12-O-tetradecanoylphorbol-13-acetate and thapsigargin, act synergistically via distinct signaling pathways to stimulate gene expression.
The transcriptionally active RVL3-VL30 element contains a triple repeat of TGACTCC, a sequence nearly identical to the AP-1 binding site. However, 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulation was unable to elicit chloramphenicol acetyltransferase (CAT) expression from a construct containing these AP-1-like sequences upstream of the thymidine kinase promoter present in pTES. Endothelin, which activates protein kinase C (pkC) and elevates intracellular Ca2+ in Rat-1 cells, was effective in stimulating CAT expression from the VL30-pTES construct. We attempted to assess the relative importance of these second messenger systems by stimulating each pathway separately with exogenous agonists. We determined that neither stimulation of pkC by the tumor promoter TPA nor elevation of intracellular Ca2+ by the tumor promoter thapsigargin was sufficient to stimulate CAT expression from the VL30-pTES vector. When combined, the two tumor promoters induced a synergistic increase in CAT expression. Our data indicate that elevation of intracellular Ca2+ by thapsigargin was not required for full activation of pkC by TPA. First, TPA was able to stimulate expression of other genes in Rat-1 cells, indicating full activation of pkC. Second, thapsigargin synergized effectively with epidermal growth factor to stimulate CAT activity from the VL30-pTES construct in cells depleted of pkC activity by chronic TPA treatment. The permissive effects of thapsigargin on gene expression were also observed for an endogenous gene, transin/stromelysin. The permissive effects of elevated intracellular Ca2+ levels may represent a general mechanism for the stimulation of some genes by pkC-mediated pathways.


Coexistence of social inequalities in undernutrition and obesity in preschool children: population based cross sectional study.
To test for the coexistence of social inequalities in undernutrition and obesity in preschool children. Retrospective, cross sectional, study of routinely collected data from 74 500 children aged 39-42 months in 1998/99. Main outcome measures were weight, height, sex, and age routinely recorded by health visitors. Body mass index (BMI) standardised for age and sex, relative to UK 1990 reference data, was used to define undernutrition (BMI <2nd centile) and obesity (BMI >95th centile; BMI >98th centile). Social deprivation was assessed as Carstairs deprivation category (1 = most affluent to 7 = most deprived). Both undernutrition (3.3%) and obesity (8.5% above 95th centile; 4.3% above 98th centile) significantly exceeded expected frequencies from UK 1990 reference data. Undernutrition and obesity were significantly more common in the more deprived families. Odds ratios in deprivation category 7 relative to category 1 were 1.51 (95% CI 1.22 to 1.87) for undernutrition (BMI <2nd centile) and 1.30 (95% CI 1.05 to 1.60) for obesity (BMI >98th centile). The cumulative prevalence of under and overnutrition (malnutrition) in the most deprived group was 9.5% compared to 6.9% in the least deprived group. Undernutrition and obesity are significantly more common than expected in young children and strongly associated with social deprivation. Both undernutrition and obesity have adverse short and long term health effects. Public health strategies need to tackle malnutrition (both undernutrition and obesity) in children and take into consideration the association with social deprivation.


Standards for photometry.
A survey is given of the standards used in photometry and spectroradiometry. After an introduction in Sec. I, the candela and lumen standards are discussed in Sec. II. Some problems related to heterochromatic photometry and the changes in the IPTS are mentioned in Secs. II.B and II.C, respectively. Section III deals with standards for spectroradiometry-the tungsten strip lamp, the anode of the carbon arc, and the high pressure xenon arc-and also with some irradiance standards. A comparison of photometric and radiometric standards is given in Sec. IV. It is concluded that with the present standards an accuracy of 1% is hardly obtainable.


Shorter Axial Length Is a Risk Factor for Proliferative Vitreoretinopathy Grade C in Eyes Unmodified by Surgical Invasion.
To investigate the risk factors for the development of proliferative vitreoretinopathy grade C (PVR-C), independent of prior surgical invasion. Patients who underwent surgery for rhegmatogenous retinal detachment were prospectively registered with the Japan-Retinal Detachment Registry, organized by the Japanese Retina and Vitreous Society, between February 2016 and March 2017. Data obtained from general ophthalmic examinations performed before and at 1, 3, and 6 months after surgery were analyzed. We included 2013 eyes of 2013 patients (men, 1326 (65.9%); mean age, 55.2 ± 15.2 years) from amongst 3446 registered patients. Preoperative PVR-C was observed in 3.6% of patients. Propensity score matching revealed that a shorter axial length (AL) was a risk factor for preoperative PVR-C (OR (Odds Ratio), 0.81; 95% CI (Confidence Interval), 0.69 to 0.96; p = 0.015), which was a risk factor for surgical failure (OR, 4.22; 95% CI, 1.12 to 15.93; p = 0.034); the association was particularly significant for eyes with an AL < 25.0 mm (p = 0.016), while it was insignificant for eyes with an AL ≥ 25.0 mm. A shorter AL was related to the development of PVR-C before surgical invasion. Our results will help elucidate the fundamental pathogenesis of PVR and caution clinicians to meticulously examine eyes with a shorter AL to detect retinal detachment before PVR development.


HLA class II associations with rheumatic heart disease among clinically homogeneous patients in children in Latvia.
Genetic control of immune reactions has a major role in the development of rheumatic heart disease (RHD) and differs between patients with rheumatic fever (RF). Some authors think the risk of acquiring RHD is associated with the HLA class II DR and DQ loci, but other views exist, due to the various HLA-typing methods and ways of grouping cases. Our goal was to determine the relations between HLA class II alleles and risk of or protection from RF in patients with relatively homogeneous clinical manifestations. A total of 70 RF patients under the age of 18 years were surveyed in Latvia. HLA genotyping of DRB1*01 to DRB1*18 and DQB1*0201-202, *0301-305, *0401-402, *0501-504, and *0601-608 was performed using polymerase chain reaction sequence-specific primers. Data for a control group of 100 healthy individuals typed for HLA by the same method were available from the databank of the Immunology Institute of Latvia. Of the RF patients, 47 had RHD and 8 had Sydenham's chorea. We concluded that HLA class II DRB1*07-DQB1*0401-2 and DRB1*07-DQB1*0302 could be the risk alleles and HLA class II DRB1*06 and DQB1*0602-8, the protective ones. Patients with mitral valve regurgitation more often had DRB1*07 and DQB1*0401-2, and patients with multivalvular lesions more often had DRB1*07 and DQB1*0302. In Sydenham's chorea patients, the DQB1*0401-2 allele was more frequent. Genotyping control showed a high risk of RF and RHD in patients with DRB1*01-DQB1*0301-DRB1*07-DQB1*0302 and DRB1*15-DQB1*0302-DRB1*07-DQB1*0303.


First Report of Root Rot on Pulsatilla koreana Caused by Fusarium oxysporum in China.
Windflowers (Pulsatilla spp.) are perennial medicinal plants in the family Ranunculaceae with high economic as well as medicinal value in China. It is commonly used as traditional Chinese medicine (1). In May 2012, a root rot disease was observed on windflower (Pulsatilla koreana Nakai) at flowering stages in fields of Liaoning Province, China. The diseased area was estimated to be over 500 ha in the province and the yield was reduced by 30% on average with up to 45% yield losses in some fields. As the disease progressed, brown lesion production extended onto lateral and main roots, and aboveground tissues shriveled and decayed; in severe cases, white mycelium was clearly visible on diseased root tissue. Isolations from symptomatic roots were made on potato dextrose agar (PDA) and single-spore cultures were obtained. Colonies were initially white, but became pale violet with age, and purple pigments were produced in the agar. Microconidia were abundant, unicellular, oval to reniform, and ranged from 5.6 to 13.1 (9.3) × 2.8 to 4.2 (3.2) μm. Macroconidia were sparse, three-septate, slightly curved, and ranged from 21.9 to 39.4 (31.2) × 3.4 to 4.5 (3.9) μm. The isolated fungus was morphologically similar to Fusarium oxysporum (2). Two isolates were selected for molecular identification, and the internal transcribed spacer (ITS) region of rDNA was amplified using the primers ITS1/ITS4 (3) and sequenced. The obtained sequences (GenBank Accession Nos. JX669525 and JX669526) showed 99% homology with the sequences of F. oxysporum in GenBank (GQ121303). For pathogenicity tests, the isolate was cultured on PDA for 10 days at 25°C. Inoculations were performed on 10 healthy P. koreana plants by spraying a conidial suspension (2.0 × 105 microconidia ml-1) on roots previously wounded with a metal needle. Ten non-treated plants used as controls were sprayed with distilled water. The inoculated plants were incubated at 25°C under conditions of 12/12 h (light and dark). After 2 weeks, root rot symptoms were similar to the original symptoms observed under field conditions. No disease was observed on water-inoculated control plants. The same fungus was reisolated from the roots of infected plants, satisfying Koch's postulates. To our knowledge, this is the first report of F. oxysporum on P. koreana in China. The disease was hitherto scarcely reported in any other countries, and may deserve more attention in the future. References: (1) S. C. Bang et al. J. Nat. Prod. 68:268, 2005. (2) J. F. Leslie and B. A. Summerell. The Fusarium Laboratory Manual. Blackwell Professional, Ames, IA, 2006. (3) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, 1990.


Multidimensional solid-state NMR spectroscopy of plant cell walls.
Plant biomass has become an important source of bio-renewable energy in modern society. The molecular structure of plant cell walls is difficult to characterize by most atomic-resolution techniques due to the insoluble and disordered nature of the cell wall. Solid-state NMR (SSNMR) spectroscopy is uniquely suited for studying native hydrated plant cell walls at the molecular level with chemical resolution. Significant progress has been made in the last five years to elucidate the molecular structures and interactions of cellulose and matrix polysaccharides in plant cell walls. These studies have focused on primary cell walls of growing plants in both the dicotyledonous and grass families, as represented by the model plants Arabidopsis thaliana, Brachypodium distachyon, and Zea mays. To date, these SSNMR results have shown that 1) cellulose, hemicellulose, and pectins form a single network in the primary cell wall; 2) in dicot cell walls, the protein expansin targets the hemicellulose-enriched region of the cellulose microfibril for its wall-loosening function; and 3) primary wall cellulose has polymorphic structures that are distinct from the microbial cellulose structures. This article summarizes these key findings, and points out future directions of investigation to advance our fundamental understanding of plant cell wall structure and function.


Interaction with the histone chaperone Vps75 promotes nuclear localization and HAT activity of Rtt109 in vivo.
Modification of histones is critical for the regulation of all chromatin-templated processes. Yeast Rtt109 is a histone acetyltransferase (HAT) that acetylates H3 lysines 9, 27 and 56. Rtt109 associates with and is stabilized by Nap1 family histone chaperone Vps75. Our data suggest Vps75 and Nap1 have some overlapping functions despite their different cellular localization and histone binding specificity. We determined that Vps75 contains a classical nuclear localization signal and is imported by Kap60-Kap95. Rtt109 nuclear localization depends on Vps75, and nuclear localization of the Vps75-Rtt109 complex is not critical for Rtt109-dependent functions, suggesting Rtt109 may be able to acetylate nascent histones before nuclear import. To date, the effects of VPS75 deletion on Rtt109 function had not been separated from the resulting Rtt109 degradation; thus, we used an Rtt109 mutant lacking the Vps75-interaction domain that is stable without Vps75. Our data show that in addition to promoting Rtt109 stability, Vps75 binding is necessary for Rtt109 acetylation of the H3 tail. Direct interaction of Vps75 with H3 likely allows Rtt109 access to the histone tail. Furthermore, our genetic interaction data support the idea of Rtt109-independent functions of Vps75. In summary, our data suggest that Vps75 influences chromatin structure by regulating histone modification and through its histone chaperone functions.


Role of troponin in patients with chronic kidney disease and suspected acute coronary syndrome: a systematic review.
Patients with chronic kidney disease (CKD) have high prevalence of elevated serum troponin levels, which makes diagnosis of acute coronary syndrome (ACS) challenging. To evaluate the utility of troponin in ACS diagnosis, treatment, and prognosis among patients with CKD. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through May 2014. Studies examining elevated versus normal troponin levels in terms of their diagnostic performance in detection of ACS, effect on ACS management strategies, and prognostic value for mortality or cardiovascular events after ACS among patients with CKD. Paired reviewers selected articles for inclusion, extracted data, and graded strength of evidence (SOE). Twenty-three studies met inclusion criteria. The sensitivity of troponin T for ACS diagnosis ranged from 71% to 100%, and specificity ranged from 31% to 86% (6 studies; low SOE). The sensitivity and specificity of troponin I ranged from 43% to 94% and from 48% to 100%, respectively (8 studies; low SOE). No studies examined how troponin levels affect management strategies. Twelve studies analyzed prognostic value. Elevated levels of troponin I or troponin T were associated with higher risk for short-term death and cardiac events (low SOE). A similar trend was observed for long-term mortality with troponin I (low SOE), but less evidence was found for long-term cardiac events for troponin I and long-term outcomes for troponin T (insufficient SOE). Patients with advanced CKD tended to have worse prognoses with elevated troponin I levels than those without them (moderate SOE). Studies were heterogeneous in design and in ACS definitions and adjudication methods. In patients with CKD and suspected ACS, troponin levels can aid in identifying those with a poor prognosis, but the diagnostic utility is limited by varying estimates of sensitivity and specificity. Agency for Healthcare Research and Quality.


Follow-up for patients with obstructive sleep apnea syndrome using a portable recording device.
A home screening device, LT-200, can record data on both breathing conditions and body positions during sleep for up to 3 consecutive days in patients with obstructive sleep apnea (OSAS). We investigated the usefulness of the LT-200 device for follow-up of OSAS. Eighteen patients (age 51.0 +/- 10.8 years, mean +/- SD) were enrolled in this study. Standard polysomnography (PSG) was performed on all patients. The number of apnea/hypopnea episodes per hour (apnea/hypopnea index: AHI), the total time that nocturnal oxygen saturation was < 90% (oxygen desaturation time: ODT), and the minimum oxygen saturation during sleep (lowest Spo2) were calculated. We used the LT-200 and PSG to evaluate any improvement in the data obtained after auto-continuous positive airway pressure (auto-CPAP) therapy. AHI was also measured using the LT-200 in three sleep positions to evaluate the efficacy of the lateral position. AHI, ODT, and lowest Spo2 values did not differ significantly between the PSG and LT-200 recordings on the control and therapy nights. The LT-200 recordings showed that AHI, ODT, and lowest Spo2 tended to be better on the second night of auto-CPAP therapy than on the first. AHI was significantly lower in the right and left lateral sleep positions than that in the supine position. Our findings suggest that since the LT-200 device provides important information about the severity of OSAS, the efficacy of auto-CPAP therapy, and body position under unattended conditions in the home. It may prove to be a useful tool for following up patients.


Effect of exosome isolation methods on physicochemical properties of exosomes and clearance of exosomes from the blood circulation.
Exosomes, which are expected to be delivery systems for biomolecules such as nucleic acids, are collected by several methods. However, the effect of exosome isolation methods on the characteristics of exosomes as drug carriers, such as recovery efficiency after sterile filtration and pharmacokinetics, has not been investigated despite the importance of these characteristics for the development of exosome-based delivery systems. In the present study, exosomes collected from murine melanoma B16-BL6 cells by several methods were compared with respect to dispersibility, recovery rate after filtering, and clearance from the blood circulation in mice. The exosomes were collected by three ultracentrifugation-based methods: simple ultracentrifugation/pelleting (pelleting method), ultracentrifugation with an iodixanol cushion (cushion method), and ultracentrifugation on an iodixanol density gradient (gradient method). The isolation methods had little effect on the particle number of exosomes. In contrast, transmission electron microscopy observation and size distribution measurement using tunable resistive pulse sensing indicated that the exosomes of the gradient method were more dispersed than the others. The exosomes were labeled with Gaussia luciferase and intravenously injected into mice. Clearance of injected exosomes from the blood circulation did not significantly change with isolation methods. When the exosomes were filtered using a 0.2-μm filter, the recovery rate was 82% for the exosomes of the gradient method, whereas it was less than 50% for the others. These results indicate that the exosome isolation method markedly affects the dispersibility and filtration efficiency of the exosomes.


Influence of Filler Composition on the Refractive Index of Four Different Enamel Shades of Composite Resins.
The purpose of this study was to measure the refractive index of four commercially available enamel resin composites, using optical coherence tomography (OCT) and their relationship with the atomic composition of the composite resin fillers utilizing an energy-dispersive X-ray fluorescence spectrometer (EDX). Four different enamel composites, namely Enamel HRi color UE3, Enamel HFO color GE3, Vit-l-escence color Pearl Frost, and Amelogen Plus color Enamel White were tested. For each composite, disks with different thicknesses were fabricated and then light-cured according to the manufacturer's instructions. The disks were then stored in deionized water under 36.5 °C for at least 7 days. Each of the samples from the four different groups was measured in five distinctive points to analyze the optical and physical length using optical coherence tomography (OCT). Elemental analysis of all four different enamel shades of the composite was done using an EDX. The filler contents showed interesting differences in elemental composition and concentration; however, Si seemed to be a common filler component. The HRi composite presented a distinctive composition compared to other materials and was the only composite that showed a smaller percentage of SiO2, and also was the only composite that contained compounds, such as P2O5, ZnO, CaO, La2O3, and V2O5. The optical coherence tomography analysis showed the refractive index values of all tested enamel composites. Among the four different enamel composite resins tested, the enamel HRi composite demonstrated the most ideal refractive index to mimic natural enamel. The enamel HRi composite demonstrated a distinctive filler composition and this could be the main reason behind its higher refractive index. Nonetheless, it remains unclear how much of an impact this feature has in the final esthetic outcome of anterior composite restorations, where many other optical phenomena are also important. The clinical success of any esthetic restorative procedure depends on diagnosing the proper treatment plan and also on executing this treatment with the right materials. On direct esthetic restorations, knowing the optical properties of such materials is fundamental, as they should be able to replicate both natural enamel and dentin. How to cite this article: Beolchi RS, Mehta D, Pelissier B, et al. Influence of Filler Composition on the Refractive Index of Four Different Enamel Shades of Composite Resins. J Contemp Dent Pract 2021;22(5):557-561.


Cardiovascular risk assessment in prediabetes and undiagnosed diabetes mellitus study: international collaboration research overview.
The study aims to develop a screening protocol for the risk of future cardiovascular disease and diabetes mellitus in people with prediabetes and undiagnosed diabetes; and to establish a framework for early identification and intervention of prediabetes including strategies for holistic management and monitoring of progression. The first phase is to identify prediabetes and undiagnosed diabetes in volunteers who are ≥18-years-old for 5 years. Point-of-care testing and questionnaire will be used to screen for prediabetes and cardiovascular disease. We anticipate screening more than 2000 individuals of both genders by the end of first phase. The second and third phases which shall run for 5-10 years will be longitudinal study involving participants identified in the first phase as having prediabetes without dyslipidaemia, or clinically established cardiovascular disease. The second phase shall focus on preventive management of risk of progress to diabetes with explicit diagnosis of cardiovascular disease. Oxidative stress measurements will be performed cum evaluation of the use of antioxidants, exercise, and nutrition. The third phase will include probing the development of diabetes and cardiovascular disease. Binomial logistic regression would be performed to generate and propose a model chart for the assessment of cardiovascular disease risk in prediabetes.


Altered expression of connexin subtypes in mesial temporal lobe epilepsy in humans.
The causes of epileptic events remain unclear. Much in vitro and in vivo experimental evidence suggests that gap junctions formed by connexins (Cxs) between neurons and/or astrocytes contribute to the generation and maintenance of seizures; however, few experiments have been conducted in humans, and those completed have shown controversial data. The authors designed a study to compare the level of expression of Cxs in hippocampi from epileptic and nonepileptic patients to assess whether an alteration of gap junction expression in epileptic tissue plays a role in seizure origin and propagation. The expression of Cxs32, -36, and -43 was studied in 47 consecutive samples of hippocampi obtained from epileptic patients who had undergone an amygdalohippocampectomy for the treatment of intractable seizure. These expression levels were compared with those in hippocampi obtained in nonepileptic patients during postmortem dissection. Immunostaining was performed to create one slide for each of the three Cxs. Each slide demonstrated multiple cells from each of six regions (CA1, CA2, CA3, CA4, dentate gyrus, and subiculum). Two independent reviewers rated each Cx-region combination according to an immunoreactive score. Across all three measures-that is, staining intensity, percentage of positively stained cells, and immunoreactive score-Cx32 appeared to be expressed at a significantly lower level in the epileptic patients compared with controls (p < 0.001 for each measure), whereas Cx43 appeared to be expressed more among the epileptic patients (p < 0.001 for each measure). There was no evidence of any differential expression of Cx36. There was, however, regional variation within each Cx subtype. For Cx36, the staining intensity was higher in the CA2 region in the epilepsy group. The increase in Cx43, decrease in Cx32, and preservation of Cx36 expression in hippocampi from epileptic persons could play a role in the development of seizures in patients with temporal sclerosis. Additional studies must be completed to understand this mechanism better.


Progressive disseminated histoplasmosis in the HIV population in Europe in the HAART era. Case report and literature review.
In highly endemic areas, up to 20 % of human immunodeficiency virus (HIV)-infected persons will develop progressive disseminated histoplasmosis (PDH). Europe is not endemic to histoplasmosis, and the disease is mainly found in immigrants often co-infected with HIV. We present a case of a patient with HIV and PDH highlighting the possible diagnostic difficulties that may arise in a non-endemic area and review the literature of histoplasmosis in the context of HIV infection with special focus on Europe. When cellular immunity wanes (usually at CD4 T-lymphocyte counts <150 cells/μL) histoplasma infection, acquired earlier, can reactivate and disseminate. PDH is an acquired immune deficiency syndrome(AIDS)-defining disease and a life-threatening infection, with a clinical spectrum ranging from an acute, fatal course with lung infiltrates and respiratory failure, shock, coagulopathy and multi-organ failure, to a more subacute disease with focal organ involvement, pancytopenia and hepatosplenomegaly. Mortality rates remain high for untreated patients, but early diagnosis, proper antifungal treatment and early initiation of antiretroviral therapy have improved the prognosis. European infectious diseases physicians, microbiologists and pathologists must be aware of histoplasmosis, particularly when facing HIV-infected immigrants from endemic areas. This is increasingly important due to migration and travel activities from these areas.


Fine-tuning the prediction of sequences cleaved by signal peptidase II: a curated set of proven and predicted lipoproteins of Escherichia coli K-12.
A curated set of 81 proven and 44 predicted lipoproteins of Escherichia coli K-12 was defined with the combined use of a literature survey, a variety of predictive tools and human expertise. The well-documented Gram-negative proteome of E. coli K-12 was chosen to assess how the different approaches complement each other and to ensure a stable definition of a consistent set of lipoproteins. The results of detailed analysis of such proteins at the level of a single proteome are presented, corroborated and rationalized.


Examining non-structural retrofitting status of teaching hospitals in Kerman against disasters.
Continuous services provision of a hospital before and after a disaster is one of the most prominent issues that all people, especially the authorities must take into huge consideration. Concerning the experiences of previous earthquakes, the role and importance of nonstructural components becomes increasingly clear in the uninterrupted services of hospitals. In this study, non-structural retrofitting status of Kerman teaching hospitals was evaluated against natural disasters. This cross-sectional study was carried out in the second half of 2014 on the teaching hospitals in Kerman (Iran). The study population consisted of all Kerman teaching hospitals. The research instrument was World Health Organization/Pan American Health Organization (WHO/PAHO) standard checklist. Data analysis was carried out using descriptive statistics through SPSS 19. One hospital had a low retrofitting level, two hospitals had an average level and one had a high level. In the examined hospitals in this study, the medical gas section had the lowest preparedness against natural disasters, while the office, warehouse and furniture section had the highest resistance. Generally, the non-structural retrofitting status was 50% in one hospital and was between 65% and 85% in other hospitals. Generally, the retrofitting status of hospitals was not at the ideal condition, most hospitals were in average condition. Concerning the high risk of hospitals in disasters, it is necessary that senior executives and managers of Kerman Province and Kerman University of Medical Sciences take some measures to retrofit these buildings and to reduce the risk of vulnerability.


A comparison of medium-term survival between peritoneal dialysis and haemodialysis in accordance with the initial vascular access.
A study published in 2011 showed that patients in the Canary Islands, who were incident in peritoneal dialysis (PD) had better survival than those who were incident in hemodialysis (HD). Since initiating hemodialysis with central venous catheter is associated with worse prognosis, it would be possible that the initial vascular access influences the results of survival comparison between both groups. To conduct a comparative medium-term survival study of patients incident in renal replacement therapy with different modalities in our community, classifying those incident in hemodialysis according to the initial vascular access: established arteriovenous vascular access or central venous catheter. Retrospective longitudinal cohort study including all patients who were incident in renal replacement therapy between January 2005 and December 2010, with follow-up until December 2011, in three large hospitals of the Canary Islands. Patients were classified according to the initial modality: PD, HD with established vascular access (HD-FAV) or HD with central venous catheter (HD-Cat). Kaplan-Meier survival curves were estimated for each group and a Cox proportional hazards survival model was used to estimate relative mortality risk for DP as compared to HD-FAV and HD-Cat, adjusting for age and Charlson comorbidity index. An equivalent analysis was then conducted on subgroups defined by age or by the presence of diabetes. 1110 patients were included, with a median age of 63 years, 56% of them were diabetic. A Kaplan-Meier analysis showed better survival for PD (66 months) as compared to HD-Cat (41 months), Log Rank p<.001, with no difference between DP and HD-FAV (67 months). Cox regression RR of mortality for HD-Cat versus PD was 2.270 (1.573-3.276); p<.001; no differences were found between HD-FAV and PD patients 0.993 (0.646-1.525) n.s. Subgroup analysis showed equivalent results for diabetic and non-diabetic patients as well as for younger or older ones. better survival of PD patients as compared to HD ones, observed in the Canary Islands, seems to be based on incident HD patients with central venous catheter, while no differences were found between PD and HD with established vascular access. These results could suggest that patients in our community, for whom a vascular access cannot be achieved in predialysis, could have better survival if PD is offered as initial technique, at least until a vascular access is available.


Use of an Elastomeric Knee Brace in Patellofemoral Pain Syndrome: Short-Term Results.
Purpose This article verifies the effectiveness of a new brace on patellofemoral pain syndrome (PFPS) in adjunct to a specifically developed rehabilitation program. Methods Two groups of 30 patients with PFPS were prospectively and randomly allocated to a rehabilitation protocol, with (group A) or without (group B) the use of a specific brace. All the patients were assessed at 3, 6, and 12 months using the disease-specific Kujala scale and a visual analog scale (VAS) for pain; time to return to sport and patient satisfaction with the brace were also recorded. Results Kujala scale's values showed constant and progressive improvement. The mean score at 6 months was 79.8 ± 6.8 points in group A and 76.8 ± 8.6 in group B, rising at 12 months to 80.9 ± 7.5 in group A and 78.4 ± 8.3 in group B. VAS scores significantly differed ( p < 0.05) between the two groups at both 6 and 12 months; the score recorded at 12 months was 0.9 ± 1.3 in the brace-treated group and 1.8 ± 1.6 in the controls. The patients who used a brace showed a quicker return to sports and 75% of the patients in this group were satisfied. Conclusion All the scores improved progressively in both groups. The most significant improvement concerned pain, showing that the brace used in this study may allow a better subjective outcome and a quicker return to sport. Level of Evidence Level II, prospective randomized controlled trial.


A New Window into the Human Alloresponse.
Alloreactive T lymphocytes are the primary mediators of allograft rejection. The size and diversity of the HLA-alloreactive T cell repertoire has thus far precluded the ability to follow these T cells and thereby to understand their fate in human transplant recipients. This review summarizes the history, challenges, and recent advances in the study of alloreactive T cells. We highlight the historical development of assays to measure alloreactivity and discuss how high-throughput T cell receptor (TCR) sequencing-based assays can provide a new window into the fate of alloreactive T cells in human transplant recipients. A specific approach combining a classical in vitro assay, the mixed lymphocyte reaction, with deep T cell receptor sequencing is described as a tool to track the donor-reactive T cell repertoire for any specific HLA-mismatched donor-recipient pair. This assay can provide mechanistic insights and has potential as a noninvasive, highly specific biomarker for rejection and tolerance.


The lunar cycle: effects on human and animal behavior and physiology.
Human and animal physiology are subject to seasonal, lunar, and circadian rhythms. Although the seasonal and circadian rhythms have been fairly well described, little is known about the effects of the lunar cycle on the behavior and physiology of humans and animals. The lunar cycle has an impact on human reproduction, in particular fertility, menstruation, and birth rate. Melatonin levels appear to correlate with the menstrual cycle. Admittance to hospitals and emergency units because of various causes (cardiovascular and acute coronary events, variceal hemorrhage, diarrhea, urinary retention) correlated with moon phases. In addition, other events associated with human behavior, such as traffic accidents, crimes, and suicides, appeared to be influenced by the lunar cycle. However, a number of reports find no correlation between the lunar cycle and human reproduction and admittance to clinics and emergency units. Animal studies revealed that the lunar cycle may affect hormonal changes early in phylogenesis (insects). In fish the lunar clock influences reproduction and involves the hypothalamus-pituitary-gonadal axis. In birds, the daily variations in melatonin and corticosterone disappear during full-moon days. The lunar cycle also exerts effects on laboratory rats with regard to taste sensitivity and the ultrastructure of pineal gland cells. Cyclic variations related to the moon's phases in the magnitude of the humoral immune response of mice to polivinylpyrrolidone and sheep erythrocytes were also described. It is suggested that melatonin and endogenous steroids may mediate the described cyclic alterations of physiological processes. The release of neurohormones may be triggered by the electromagnetic radiation and/or the gravitational pull of the moon. Although the exact mechanism of the moon's influence on humans and animals awaits further exploration, knowledge of this kind of biorhythm may be helpful in police surveillance, medical practice, and investigations involving laboratory animals.


A Partial Calcium-Free Linker Confers Flexibility to Inner-Ear Protocadherin-15.
Tip links of the inner ear are protein filaments essential for hearing and balance. Two atypical cadherins, cadherin-23 and protocadherin-15, interact in a Ca2+-dependent manner to form tip links. The largely unknown structure and mechanics of these proteins are integral to understanding how tip links pull on ion channels to initiate sensory perception. Protocadherin-15 has 11 extracellular cadherin (EC) repeats. Its EC3-4 linker lacks several of the canonical Ca2+-binding residues, and contains an aspartate-to-alanine polymorphism (D414A) under positive selection in East Asian populations. We present structures of protocadherin-15 EC3-5 featuring two Ca2+-binding linker regions: canonical EC4-5 linker binding three Ca2+ ions, and non-canonical EC3-4 linker binding only two Ca2+ ions. Our structures and biochemical assays reveal little difference between the D414 and D414A variants. Simulations predict that the partial Ca2+-free EC3-4 linker exhibits increased flexural flexibility without compromised mechanical strength, providing insight into the dynamics of tip links and other atypical cadherins.


Prolyl-4-Hydroxylases Inhibitor Stabilizes HIF-1α and Increases Mitophagy to Reduce Cell Death After Experimental Retinal Detachment.
This study investigated the neuroprotective effect against photoreceptor cell death using prolyl-4-hydroxylases inhibitor (PHI), an HIF-1α stabilizer, in experimental retinal detachment (RD). RD was created in Brown Norway rats by subretinal injection of 1% sodium hyaluronate. FG-4592 (a PHI, 25 mg/kg) or a vehicle was administered every 2 days with retro-orbital injection. Photoreceptor death was evaluated by TdT-dUTP terminal nick-end labeling (TUNEL) assay 3 days after RD and by the thickness of the outer nuclear layer 7 days after RD. The mitophagy-related markers Hypoxia Inducible Factor 1α (HIF-1α), BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), autophagy-related gene 5 (Atg5), microtubule-associated protein 1 light chain 3 beta (LC3B), and FUN14 domain containing 1 (FUNDC1) were detected by Western blot and immunofluorescence. Transmission electron microscopy was used to observe ultramicro-morphological changes. Mitochondrial damage was evaluated by the measurement of reactive oxygen species (ROS) by in situ ROS detection with dihydroethidium. The accumulation of HIF-1α and BNIP3 significantly increased after PHI treatment (P < 0.05), the pattern of Atg5 and LC3 changed, and FUNDC1 and LC3 were colocated. More autophagic vacuoles engulfing mitochondria were observed in transmission electron microscopy sections after PHI treatment when compared with the control. ROS significantly decreased in the PHI-treatment group (P < 0.05). This resulted in reduced TUNEL-positive photoreceptors 3 days after RD and an increased thickness of the outer nuclear layer 7 days after RD (P < 0.05). HIF-1α stabilization as a result of PHI treatment, along with the enhancement of mitophagy, could provide protection against photoreceptor injury following RD, which might be mediated by excessive ROS generation.


A prediction algorithm for first onset of major depression in the general population: development and validation.
Prediction algorithms are useful for making clinical decisions and for population health planning. However, such prediction algorithms for first onset of major depression do not exist. The objective of this study was to develop and validate a prediction algorithm for first onset of major depression in the general population. Longitudinal study design with approximate 3-year follow-up. The study was based on data from a nationally representative sample of the US general population. A total of 28 059 individuals who participated in Waves 1 and 2 of the US National Epidemiologic Survey on Alcohol and Related Conditions and who had not had major depression at Wave 1 were included. The prediction algorithm was developed using logistic regression modelling in 21 813 participants from three census regions. The algorithm was validated in participants from the 4th census region (n=6246). Major depression occurred since Wave 1 of the National Epidemiologic Survey on Alcohol and Related Conditions, assessed by the Alcohol Use Disorder and Associated Disabilities Interview Schedule-diagnostic and statistical manual for mental disorders IV. A prediction algorithm containing 17 unique risk factors was developed. The algorithm had good discriminative power (C statistics=0.7538, 95% CI 0.7378 to 0.7699) and excellent calibration (F-adjusted test=1.00, p=0.448) with the weighted data. In the validation sample, the algorithm had a C statistic of 0.7259 and excellent calibration (Hosmer-Lemeshow χ(2)=3.41, p=0.906). The developed prediction algorithm has good discrimination and calibration capacity. It can be used by clinicians, mental health policy-makers and service planners and the general public to predict future risk of having major depression. The application of the algorithm may lead to increased personalisation of treatment, better clinical decisions and more optimal mental health service planning.


Modelling sexual transmission of HIV: testing the assumptions, validating the predictions.
To discuss the role of mathematical models of sexual transmission of HIV: the methods used and their impact. We use mathematical modelling of 'universal test and treat' as a case study to illustrate wider issues relevant to all modelling of sexual HIV transmission. Mathematical models are used extensively in HIV epidemiology to deduce the logical conclusions arising from one or more sets of assumptions. Simple models lead to broad qualitative understanding, whereas complex models can encode more realistic assumptions and, thus, be used for predictive or operational purposes. An overreliance on model analysis in which assumptions are untested and input parameters cannot be estimated should be avoided. Simple models providing bold assertions have provided compelling arguments in recent public health policy, but may not adequately reflect the uncertainty inherent in the analysis.


Generation of monomeric reversibly switchable red fluorescent proteins for far-field fluorescence nanoscopy.
Reversibly switchable fluorescent proteins (RSFPs) are GFP-like proteins that may be repeatedly switched by irradiation with light from a fluorescent to a nonfluorescent state, and vice versa. They can be utilized as genetically encodable probes and bear large potential for a wide array of applications, in particular for new protein tracking schemes and subdiffraction resolution microscopy. However, the currently described monomeric RSFPs emit only blue-green or green fluorescence; the spectral window for their use is thus rather limited. Using a semirational engineering approach based on the crystal structure of the monomeric nonswitchable red fluorescent protein mCherry, we generated rsCherry and rsCherryRev. These two novel red fluorescent RSFPs exhibit fluorescence emission maxima at approximately 610 nm. They display antagonistic switching modes, i.e., in rsCherry irradiation with yellow light induces the off-to-on transition and blue light the on-to-off transition, whereas in rsCherryRev the effects of the switching wavelengths are reversed. We demonstrate time-lapse live-cell subdiffraction microscopy by imaging rsCherryRev targeted to the endoplasmic reticulum utilizing the switching and localization of single molecules.


Aminoglycoside-induced damage in the statocyst of the longfin inshore squid, Doryteuthis pealeii.
Squid are a significant component of the marine biomass and are a long-established model organism in experimental neurophysiology. The squid statocyst senses linear and angular acceleration and is the best candidate for mediating squid auditory responses, but its physiology and morphology are rarely studied. The statocyst contains mechano-sensitive hair cells that resemble hair cells in the vestibular and auditory systems of other animals. We examined whether squid statocyst hair cells are sensitive to aminoglycosides, a group of antibiotics that are ototoxic in fish, birds, and mammals. To assess aminoglycoside-induced damage, we used immunofluorescent methods to image the major cell types in the statocyst of longfin squid (Doryteuthis pealeii). Statocysts of live, anesthetized squid were injected with either a buffered saline solution or neomycin at concentrations ranging from 0.05 to 3.0 mmol l(-1). The statocyst hair cells of the macula statica princeps were examined 5 h post-treatment. Anti-acetylated tubulin staining showed no morphological differences between the hair cells of saline-injected and non-injected statocysts. The hair cell bundles of the macula statica princeps in aminoglycoside-injected statocysts were either missing or damaged, with the amount of damage being dose-dependent. The proportion of missing hair cells did not increase at the same rate as damaged cells, suggesting that neomycin treatment affects hair cells in a nonlethal manner. These experiments provide a reliable method for imaging squid hair cells. Further, aminoglycosides can be used to induce hair cell damage in a primary sensory area of the statocyst of squid. Such results support further studies on loss of hearing and balance in squid.


Whispering gallery mode resonators with J-aggregates.
We have studied the optical properties of a hybrid system consisting of cyanine dye J-aggregates attached to a spherical microcavity. A periodic structure of narrow peaks was observed in the photoluminescence spectrum of the J-aggregates, arising from the coupling between the emission of J-aggregates and the whispering gallery modes (WGMs) of the microcavity. The most striking result of our study is the observation of polarization sensitive mode damping caused by re-absorption of J-aggregate emission. This effect manifests itself in dominating emission from TM modes in the spectral region of J-aggregates absorption band where the TE modes are strongly suppressed. In contrast, the TE modes totally dominate emission spectrum in the region where absorption is negligible. We also demonstrate that the emission intensity can be further enhanced by depositing a hybrid layer of J-aggregates and Ag nanoparticles onto the spherical microcavity. Owing to the concerted action of WGMs and plasmonic hot spots in the Ag aggregates, we observe an enhanced Raman signal from the J-aggregates. Microcavities covered by J-aggregates and plasmonic nanoparticles could be thus useful for a variety of photonic applications in basic science and technology.


Towards the flower economics spectrum.
Understanding how floral traits affect reproduction is key for understanding genetic diversity, speciation, and trait evolution in the face of global changes and pollinator decline. However, there has not yet been a unified framework to characterize the major trade-offs and axes of floral trait variation. Here, we propose the development of a floral economics spectrum (FES) that incorporates the multiple pathways by which floral traits can be shaped by multiple agents of selection acting on multiple flower functions. For example, while pollinator-mediated selection has been considered the primary factor affecting flower evolution, selection by nonpollinator agents can reinforce or oppose pollinator selection, and, therefore, affect floral trait variation. In addition to pollinators, the FES should consider nonpollinator biotic agents and floral physiological costs, broadening the drivers of floral traits beyond pollinators. We discuss how coordinated evolution and trade-offs among floral traits and between floral and vegetative traits may influence the distribution of floral traits across biomes and lineages, thereby influencing organismal evolution and community assembly.


The SEM Risk Behavior (SRB) Model: A New Conceptual Model of how Pornography Influences the Sexual Intentions and HIV Risk Behavior of MSM.
While the effects of sexually explicit media (SEM) on heterosexuals' sexual intentions and behaviors have been studied, little is known about the consumption and possible influence of SEM among men who have sex with men (MSM). Importantly, conceptual models of how Internet-based SEM influences behavior are lacking. Seventy-nine MSM participated in online focus groups about their SEM viewing preferences and sexual behavior. Twenty-three participants reported recent exposure to a new behavior via SEM. Whether participants modified their sexual intentions and/or engaged in the new behavior depended on three factors: arousal when imagining the behavior, pleasure when attempting the behavior, and trust between sex partners. Based on MSM's experience, we advance a model of how viewing a new sexual behavior in SEM influences sexual intentions and behaviors. The model includes five paths. Three paths result in the maintenance of sexual intentions and behaviors. One path results in a modification of sexual intentions while maintaining previous sexual behaviors, and one path results in a modification of both sexual intentions and behaviors. With this model, researchers have a framework to test associations between SEM consumption and sexual intentions and behavior, and public health programs have a framework to conceptualize SEM-based HIV/STI prevention programs.


Dual manganese-enhanced and delayed gadolinium-enhanced MRI detects myocardial border zone injury in a pig ischemia-reperfusion model.
Gadolinium (Gd)-based delayed-enhancement MRI (DEMRI) identifies nonviable myocardium but is nonspecific and may overestimate nonviable territory. Manganese (Mn(2+))-enhanced MRI (MEMRI) denotes specific Mn(2+) uptake into viable cardiomyocytes. We performed a dual-contrast myocardial assessment in a porcine ischemia-reperfusion (IR) model to test the hypothesis that combined DEMRI and MEMRI identifies viable infarct border zone (BZ) myocardium in vivo. Sixty-minute left anterior descending coronary artery IR injury was induced in 13 adult swine. Twenty-one days post-IR, 3-T cardiac MRI was performed. MEMRI was obtained after injection of 0.7 mL/kg Mn(2+) contrast agent. DEMRI was then acquired after injection of 0.2 mmol/kg Gd. Left ventricular (LV) mass, infarct, and function were analyzed. Subtraction of MEMRI defect from DEMRI signal identified injured BZ myocardium. Explanted hearts were analyzed by 2,3,5-triphenyltetrazolium chloride stain and tissue electron microscopy to compare infarct, BZ, and remote myocardium. Average LV ejection fraction was reduced (30±7%). MEMRI and DEMRI infarct volumes correlated with 2,3,5-triphenyltetrazolium chloride stain analysis (MEMRI, r=0.78; DEMRI, r=0.75; P<0.004). MEMRI infarct volume percentage was significantly lower than that of DEMRI (14±4% versus 23±4%; P<0.05). BZ MEMRI signal-to-noise ratio (SNR) was intermediate to remote and core infarct SNR (7.5±2.8 versus 13.2±3.4 and 2.9±1.6; P<0.0001), and DEMRI BZ SNR tended to be intermediate to remote and core infarct SNR (8.4±5.4 versus 3.3±0.6 and 14.3±6.6; P>0.05). Tissue electron microscopy analysis exhibited preserved cell structure in BZ cardiomyocytes despite transmural DEMRI enhancement. The dual-contrast MEMRI-DEMRI detects BZ viability within DEMRI infarct zones. This approach may identify injured, at-risk myocardium in ischemic cardiomyopathy.


The risk of amenorrhea is related to chemotherapy-induced leucopenia in breast cancer patients receiving epirubicin and taxane based chemotherapy.
Chemotherapy-induced amenorrhea (CIA) is common in young breast cancer patients. The incidence of CIA associated with regimens involving epirubicin and taxane was not well known. Furthermore, previous studies suggested leucopenia and amenorrhea may reflect inter-individual variations in pharmacokinetics. The purpose of this study was to investigate the association between leucopenia after first cycle of chemotherapy and CIA in young breast cancer patients receiving epirubicin and taxane based chemotherapy. Furthermore, the incidence of CIA was also assessed. Between October 2008 and March 2010, 186 consecutive premenopausal patients, treated with epirubicin and taxane based chemotherapy, were recruited. Information about CIA was collected by telephone and out-patient clinic. Of these 186 patients, data from 165 patients were included and analyzed. Of all 165 patients, CIA occurred in 72 patients (43.64%). In multivariate analysis, age older than 40 y (OR: 16.10, 95% CI: 6.34-40.88, P<0.001) and previous childbearing (OR: 3.17, 95% CI: 1.06-9.47, P = 0.038) were significantly associated with probability of CIA. Compared to patients treated without taxane, patients treated with taxane-contained regimens did not have a significantly higher rate of CIA (P>0.05). The rate of CIA in leucopenia group (52.56%) was significantly higher than that in normal leukocyte group (34.62%) (P = 0.024). In patients treated with a FEC regimen (cyclophosphamide, epirubicin and 5-fluorouracil), the rate of CIA in leucopenia group (59.57%) was significantly higher than that in normal leukocyte group (36.84%) (P = 0.037). Age at diagnosis and previous childbearing were both found to significantly increase the risk of CIA, whereas additional taxane was not associated with increased rate of CIA. Importantly, leucopenia after first cycle of chemotherapy was associated with increased risk of CIA, which suggested that leucopenia may be an early predictor of chemotherapy-induced infertility.


Customers' Perceptions of Compliance with a Tobacco Control Law in Restaurants in Hanoi, Vietnam: A Cross-Sectional Study.
The Tobacco Harm Prevention Law has been promulgated in 2012 in Vietnam, prohibiting smoking in public places such as restaurants except for designated smoking areas. However, currently, evidence about Vietnamese customers' and restaurants' compliance with the Law is constrained. This study aimed to explore customers' perceptions; attitudes and practices towards the compliance with tobacco control regulations in the restaurants in Hanoi, Vietnam. A cross-sectional study was performed in October 2015 with 1746 customers in 176 communes in Hanoi, Vietnam. Data about customers' perceptions on how restaurants comply with the smoking control law and whether customers smoking actively or experienced SHS in restaurants in the last 30 days were collected. Multivariable mixed effects logistic regression model was used to determine the factors related to smoking in the restaurant. Most customers were aware of the law on Tobacco Harm Prevention (79%; n = 1320) and regulations that prohibited smoking in restaurants (78.4%; n = 1137). While 75.8% (n = 1285) of customers perceived that they did not see or rarely saw no-smoking signs, 17.7% (n = 481) of customers reported that they frequently saw direct marketing of tobacco in visited restaurants. About one-fourth of customers witnessed that the staff reminded customers not to smoke inside restaurants (28.8%; n = 313), and 65% (n = 1135) sometimes or always were exposed to secondhand smoke in their visited restaurants. People who were female (OR = 0.02, 95% CI = 0.01⁻0.05) were less likely to report their smoking in the restaurant than their counterparts. Those having higher age (OR = 1.03; 95% CI = 1.01⁻1.06), high school education (OR = 2.14, 95% CI = 1.07⁻4.26), being office workers (OR = 3.24, 95% CI = 1.33⁻7.92) or unemployed (OR = 4.45; 95% CI = 1.09⁻18.15) had a higher likelihood of reporting to be restaurant smokers than those having lower high education or students, respectively. This study highlighted a low level of perceived compliance with the smoke-free law in Vietnamese restaurants. Improving the monitoring systems for the enforcement of the smoking law in restaurants should be prioritized; restaurant owners should implement 100% smoke-free environments as following the best practice towards the tobacco control law along with educational campaigns to promote the awareness of restaurant owners and customers about the tobacco control law.


Antiviral therapy completion and response rates among hepatitis C patients with and without schizophrenia.
Despite disproportionately high rates of hepatitis C (HCV) among patients with severe mental illness, to date, there is scant empirical data available regarding antiviral therapy outcomes within this population. To compare antiviral therapy completion and response rates between HCV patients with vs those without schizophrenia (SCHZ). A regional Veterans Healthcare Administration database was used to identify veterans meeting criteria for this retrospective chart review. All patients confirmed to have SCHZ and to have received antiviral therapy between 1998 and 2006 (n = 30) were compared with a control group of demographically matched (HCV genotype, age, race, gender) patients with no history of SCHZ (n = 30). For HCV patients with genotype 1, antiviral completion, end of treatment response (ETR), and sustained viral response (SVR) rates did not significantly differ between groups. For those with genotypes 2 and 3 combined, antiviral therapy completion rates did not significantly differ between groups; however, the SCHZ group was significantly (P < 0.050) more likely to achieve an ETR and an SVR. For all genotypes combined, the SCHZ patients were no more likely than controls to discontinue therapy early for psychiatric symptoms, medical complications, or other adverse events, and groups did not significantly differ in terms of hospitalization rates during antiviral therapy. Our retrospective chart review suggests that patients with SCHZ complete and respond to antiviral therapy for HCV at rates comparable with those without SCHZ. Based on these data, SCHZ should not be considered a contraindication to antiviral therapy for HCV.


Behavioural support of a proposed neurocognitive connection between physical activity and improved eating behaviour in obese women.
An explanation of the association between physical activity and improved eating behaviours has recently been posited via the effect of physical activity on executive functions of the brain resulting in a reduction in the hedonic drive to overeat. Decomposition and clarification of embedded relationship through a behavioural/psychological framework was sought. Changes in theory-based psychosocial factors over 26 weeks were tested with 134 severely obese women (age 41.7±10.4 years) initiating a physical activity support treatment. Mediation and reciprocal effects analyses incorporating these changes were then computed. Significant improvements in mood, self-regulation for eating, and self-efficacy for controlled eating were found. Emanating from mood change, a reciprocal relationship between changes in the self-regulation and self-efficacy measures was found. Thus, each factor reinforced the other's change. Findings suggest a convergence of neurocognitively and behaviourally based explanations of the relations of physical activity and controlled eating. Implications for behavioural weight-loss theory and treatments were suggested.


Tumour maintenance is mediated by eNOS.
Tumour cells become addicted to the expression of initiating oncogenes like Ras, such that loss of oncogene expression in established tumours leads to tumour regression. HRas, NRas or KRas are mutated to remain in the active GTP-bound oncogenic state in many cancers. Although Ras activates several proteins to initiate human tumour growth, only PI3K, through activation of protein kinase B (PKB; also known as AKT), must remain activated by oncogenic Ras to maintain this growth. Here we show that blocking phosphorylation of the AKT substrate, endothelial nitric oxide synthase (eNOS or NOS3), inhibits tumour initiation and maintenance. Moreover, eNOS enhances the nitrosylation and activation of endogenous wild-type Ras proteins, which are required throughout tumorigenesis. We suggest that activation of the PI3K-AKT-eNOS-(wild-type) Ras pathway by oncogenic Ras in cancer cells is required to initiate and maintain tumour growth.


Two-color dual-beam backscatter laser Doppler velocimeter.
A laser Doppler velocimeter has been developed that uses two of the colors emitted from an argon-ion laser for the simultaneous measurement of orthogonal velocities. Designed for use in a 2.13-m by 3.05-m wind tunnel, it is capable of traversing its focal volume across spatially unstable flows at scan speeds of up to 1.5 m/sec. Its optical layout and principles of operation are discussed, and the data from a typical traversal of a trailing wing-tip vortex are presented.


A multiplex method for detection of SARS-CoV-2 variants based on MALDI-TOF mass spectrometry.
The recent outbreak of the coronavirus disease 2019 (COVID-19) pandemic and the continuous evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have highlighted the significance of new detection methods for global monitoring and prevention. Although quantitative reverse transcription PCR (RT-qPCR), the current gold standard for diagnosis, performs excellently in genetic testing, its multiplexing capability is limited because of the signal crosstalk of various fluorophores. Herein, we present a highly efficient platform which combines 17-plex assays with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), enabling the targeting of 14 different mutation sites of the spike gene. Diagnosis using a set of 324 nasopharyngeal swabs or sputum clinical samples with SARS-CoV-2 MS method was identical to that with the RT-qPCR. The detection consistency of mutation sites was 97.9% (47/48) compared to Sanger sequencing without cross-reaction with other respiratory-related pathogens. Therefore, the MS method is highly potent to track and assess SARS-CoV-2 changes in a timely manner, thereby aiding the continuous response to viral variation and prevention of further transmission.


K+ transport by the OsHKT2;4 transporter from rice with atypical Na+ transport properties and competition in permeation of K+ over Mg2+ and Ca2+ ions.
Members of class II of the HKT transporters, which have thus far only been isolated from grasses, were found to mediate Na(+)-K(+) cotransport and at high Na(+) concentrations preferred Na(+)-selective transport, depending on the ionic conditions. But the physiological functions of this K(+)-transporting class II of HKT transporters remain unknown in plants, with the exception of the unique class II Na(+) transporter OsHKT2;1. The genetically tractable rice (Oryza sativa; background Nipponbare) possesses two predicted K(+)-transporting class II HKT transporter genes, OsHKT2;3 and OsHKT2;4. In this study, we have characterized the ion selectivity of the class II rice HKT transporter OsHKT2;4 in yeast and Xenopus laevis oocytes. OsHKT2;4 rescued the growth defect of a K(+) uptake-deficient yeast mutant. Green fluorescent protein-OsHKT2;4 is targeted to the plasma membrane in transgenic plant cells. OsHKT2;4-expressing oocytes exhibited strong K(+) permeability. Interestingly, however, K(+) influx in OsHKT2;4-expressing oocytes did not require stimulation by extracellular Na(+), in contrast to other class II HKT transporters. Furthermore, OsHKT2;4-mediated currents exhibited permeabilities to both Mg(2+) and Ca(2+) in the absence of competing K(+) ions. Comparative analyses of Ca(2+) and Mg(2+) permeabilities in several HKT transporters, including Arabidopsis thaliana HKT1;1 (AtHKT1;1), Triticum aestivum HKT2;1 (TaHKT2;1), OsHKT2;1, OsHKT2;2, and OsHKT2;4, revealed that only OsHKT2;4 and to a lesser degree TaHKT2;1 mediate Mg(2+) transport. Interestingly, cation competition analyses demonstrate that the selectivity of both of these class II HKT transporters for K(+) is dominant over divalent cations, suggesting that Mg(2+) and Ca(2+) transport via OsHKT2;4 may be small and would depend on competing K(+) concentrations in plants.


Properties of F1-ATPase from the uncD412 mutant of Escherichia coli.
Properties of purified F1-ATPase from Escherichia coli mutant strain AN484 (uncD412) have been studied in an attempt to understand why the amino acid substitution in the beta-subunit of this enzyme causes a tenfold reduction from normal MgATP hydrolysis rate. In most properties that were studied, uncD412 F1-ATPase resembled normal E. coli F1-ATPase. Both enzymes were found to contain a total of six adenine-nucleotide-binding sites, of which three were found to be non-exchangeable and three were exchangeable (catalytic) sites. Binding of the non-hydrolysable substrate analogue adenosine 5'-[beta gamma-imido]triphosphate (p[NH]ppA) to the three exchangeable sites showed apparent negative co-operativity. The binding affinities for p[NH]ppA, and also ADP, at the exchangeable sites were similar in the two enzymes. Both enzymes were inhibited by efrapeptin, aurovertin and p[NH]ppA, and were inactivated by dicyclohexylcarbodi-imide, 4-chloro-7-nitrobenzofurazan and p-fluorosulphonyl-benzoyl-5'-adenosine. Km values for CaATP and MgATP were similar in the two enzymes. uncD412 F1-ATPase was abnormally unstable at high pH, and dissociated into subunits readily with consequent loss of activity. The reason for the impairment of catalysis in uncD412 F1-ATPase cannot be stated with certainty from these studies. However we discuss the possibility that the mutation interrupts subunit interaction, thereby causing a partial impairment in the site-site co-operativity which is required for 'promotion' of catalysis in this enzyme.


Detection of cancer cells using SapC-DOPS nanovesicles.
Unlike normal cells, cancer cells express high levels of phosphatidylserine on the extracellular leaflet of their cell membrane. Exploiting this characteristic, our lab developed a therapeutic agent that consists of the fusogenic protein, saposin C (SapC) which is embedded in dioleoylphosphatidylserine (DOPS) vesicles. These nanovesicles selectively target cancer cells and induce apoptosis. Here we review the data supporting use of SapC-DOPS to locate tumors for surgical resection or for treatment. In addition, there is important evidence suggesting that SapC-DOPS may also prove to be an effective novel cancer therapeutic reagent. Given that SapC-DOPS is easily labeled with lipophilic dyes, it has been combined with the far-red fluorescent dye, CellVue Maroon (CVM), for tumor targeting studies. We also have used contrast agents incorporated in the SapC-DOPS nanovesicles for computed tomography and magnetic resonance imaging, and review that data here. Administered intravenously, the fluorescently labeled SapC-DOPS traversed the blood-brain tumor barrier enabling identification of brain tumors. SapC-DOPS-CVM also detected a variety of other mouse tumors in vivo, rendering them observable by optical imaging using IVIS and multi-angle rotational optical imaging. Dye is detected within 30 min and remains within tumor for at least 7 days, whereas non-tumor tissues were unstained (some dye observed in the liver was transient, likely representing degradation products). Additionally, labeled SapC-DOPS ex vivo delineated tumors in human histological specimens. SapC-DOPS can also be labeled with contrast reagents for computed tomography or magnetic resonance imaging. In conclusion, labeled SapC-DOPS provides a convenient, specific, and nontoxic method for detecting tumors while concurrently offering a therapeutic benefit.


Safety and immunogenicity of an FP9-vectored candidate tuberculosis vaccine (FP85A), alone and with candidate vaccine MVA85A in BCG-vaccinated healthy adults: a phase I clinical trial.
The safety and immunogenicity of a new candidate tuberculosis (TB) vaccine, FP85A was evaluated alone and in heterologous prime-boost regimes with another candidate TB vaccine, MVA85A. This was an open label, non-controlled, non-randomized Phase I clinical trial. Healthy previously BCG-vaccinated adult subjects were enrolled sequentially into three groups and vaccinated with FP85A alone, or both FP85A and MVA85A, with a four week interval between vaccinations. Passive and active data on adverse events were collected. Immunogenicity was evaluated by Enzyme Linked Immunospot (ELISpot), flow cytometry and Enzyme Linked Immunosorbent assay (ELISA). Most adverse events were mild and there were no vaccine-related serious adverse events. FP85A vaccination did not enhance antigen 85A-specific cellular immunity. When MVA85A vaccination was preceded by FP85A vaccination, cellular immune responses were lower compared with when MVA85A vaccination was the first immunisation. MVA85A vaccination, but not FP85A vaccination, induced anti-MVA IgG antibodies. Both MVA85A and FP85A vaccinations induced anti-FP9 IgG antibodies. In conclusion, FP85A vaccination was well tolerated but did not induce antigen-specific cellular immune responses. We hypothesize that FP85A induced anti-FP9 IgG antibodies with cross-reactivity for MVA85A, which may have mediated inhibition of the immune response to subsequent MVA85A. ClinicalTrials.gov identification number: NCT00653770.


Perioperative morbidity: lessons from recent clinical trials.
To identify the recent literature supporting the ability of anesthesiologists to impact morbidity and mortality outside of the immediate intraoperative period. Hemodynamic management designed to optimize cardiac output and stroke volume can significantly lower the risk of perioperative morbidity, and, in some cases, mortality. The implications of the POISE trial, which upended the previously accumulating data in support of indiscriminate perioperative β-blockade by demonstrating worsened outcomes, were supported by high-quality, propensity-matched, prospectively collected data. Data supporting the safety of colloid use has been threatened by the retraction of 88 publications of a single author, as well as prospective, nonrandomized data, suggesting increased renal morbidity in critically ill patients receiving synthetic colloids. Large datasets continue to suggest an association between red blood cell transfusion and mortality. Analysis of the operating room strongly implicates anesthesia providers as a potential mechanism for bacterial contamination. Anesthesiologists should consider implication of goal-directed therapy in high-risk surgical patients, adhere to the American College of Cardiology/American Heart Association guidelines with regard to perioperative β-blockade, critically assess the data to support their choice of synthetic colloids over crystalloids, explore all possible strategies for avoiding perioperative transfusion, and be cognizant of their potential contribution to perioperative infectious morbidity.


Tuberculous bowel obstruction at a university teaching hospital in Northwestern Tanzania: a surgical experience with 118 cases.
Bowel obstruction resulting from intestinal tuberculosis has been reported to be more prevalent in developing countries including Tanzania. This study was undertaken to describe the clinicopathological profile, surgical management and outcome of tuberculous intestinal obstruction in our local setting and to identify factors responsible for poor outcome among these patients. This was a prospective descriptive study of patients operated for tuberculous intestinal obstruction at Bugando Medical Centre (BMC) in northwestern Tanzania from April 2008 to March 2012. Ethical approval to conduct the study was obtained from relevant authorities. Statistical data analysis was performed using SPSS version 17.0. A total of 118 patients with tuberculous intestinal obstruction were studied. The male to female ratio was 1.8: 1. The median age was 26 years (range 11-67 years). The modal age group was 21-30 years. Thirty-one (26.3%) patients had associated pulmonary tuberculosis and 25 (21.2%) patients were HIV positive with a median CD4+ count of 225 cells /μl. Small bowel strictures were the most common operative findings accounting for 72.9% of cases. The ileo-caecal region was the commonest area of involvement in 68 (57.6%) patients. The right hemicolectomy with ileo-transverse anastomosis was the most frequent surgical procedure performed in 66 (55.9%) patients. Postoperatively all the patients received antituberculous drugs for a period of one year. Postoperative complication rate was 37.3% and surgical site infection (SSI) was the most frequent complication in 42.8% of cases. HIV positivity and low CD4+ count were the main predictors of SSI (p < 0.001). The overall median length of hospital stay was 24 days. Patients who had postoperative complications stayed longer in the hospital and this was statistically significant (p = 0.011). Mortality rate was 28.8% and it was significantly associated with co-existing medical illness, delayed presentation, HIV positivity, low CD 4 count (<200 cells/μl), ASA class and presence of complications (p < 0.001). The follow up of patients was generally poor as more than fifty percent of patients were lost to follow up. Tuberculous bowel obstruction remains rampant in our environment and contributes significantly to high morbidity and mortality. The majority of patients present late when the disease becomes complicated. A high index of suspicion, proper evaluation and therapeutic trial in suspected patients is essential for an early diagnosis and timely definitive treatment, in order to decrease the morbidity and mortality associated with this disease.


Matched pair analysis comparing surgery followed by radiotherapy and radiotherapy alone for metastatic spinal cord compression.
The appropriate treatment for MSCC is controversial. A small randomized trial showed that decompressive surgery followed by radiotherapy was superior to radiotherapy alone. That study was limited to highly selected patients. Additional studies comparing surgery plus radiotherapy to radiotherapy could better clarify the role of surgery. Data from 108 patients receiving surgery plus radiotherapy were matched to 216 patients (1:2) receiving radiotherapy alone. Groups were matched for 11 potential prognostic factors and compared for post-treatment motor function, ambulatory status, regaining ambulatory status, local control, and survival. Subgroup analyses were performed for patients receiving adequate surgery (direct decompressive surgery plus stabilization of involved vertebrae), patients receiving laminectomy, patients with solid tumors, patients with solid tumors receiving adequate surgery, and patients with solid tumors receiving laminectomy. Improvement of motor function occurred in 27% of patients after surgery plus radiotherapy and 26% after radiotherapy alone (P = .92). Post-treatment ambulatory rates were 69% after surgery plus radiotherapy and 68% after radiotherapy alone (P = .99). Of the nonambulatory patients, 30% and 26%, respectively, (P = .86) regained ambulatory status after treatment. One-year local control rates were 90% after surgery plus radiotherapy and 91% after radiotherapy alone (P = .48). One-year overall survival rates were 47% and 40%, respectively (P = .50). The subgroup analyses did not show significant differences between both groups. Surgery-related complications occurred in 11% of patients. In this study, the outcomes of the end points evaluated after radiotherapy alone appeared similar to those of surgery plus radiotherapy. A new randomized trial comparing both treatments is justified.


A journey through mapping space: characterising the statistical and metric properties of reduced representations of macromolecules.
A mapping of a macromolecule is a prescription to construct a simplified representation of the system in which only a subset of its constituent atoms is retained. As the specific choice of the mapping affects the analysis of all-atom simulations as well as the construction of coarse-grained models, the characterisation of the mapping space has recently attracted increasing attention. We here introduce a notion of scalar product and distance between reduced representations, which allows the study of the metric and topological properties of their space in a quantitative manner. Making use of a Wang-Landau enhanced sampling algorithm, we exhaustively explore such space, and examine the qualitative features of mappings in terms of their squared norm. A one-to-one correspondence with an interacting lattice gas on a finite volume leads to the emergence of discontinuous phase transitions in mapping space, which mark the boundaries between qualitatively different reduced representations of the same molecule.


Early and Intensive Dietary Counseling in Lung Cancer Patients Receiving (Chemo)Radiotherapy-A Pilot Randomized Controlled Trial.
Malnutrition is prevalent in patients undergoing (chemo)radiotherapy (RT) for lung cancer. This pilot study tested the feasibility and acceptability of delivering an intensive nutrition intervention for lung cancer patients receiving RT. Twenty-four patients with lung cancer were randomized to receive the intervention which employed a care pathway to guide intensive dietary counseling from pretreatment until 6-wk posttreatment or usual care. Nutritional, fatigue, and functional outcomes were assessed using valid and reliable questionnaires before randomization, at the start and end of RT and 1- and 3-mo post-RT. Consent rate was 57% with an overall attrition of 37%. Subject compliance with the completion of study questionnaires was 100%. A clinically important mean difference indicated greater overall satisfaction with nutritional care in the intervention group (5.00, interquartile range [IQR] 4.50-5.00; 4.00, IQR 4.00-4.00). Clinically important differences favoring the intervention were observed for weight (3.0 kg; 95% confidence interval [CI] -0.8, 6.8), fat-free mass (0.6 kg; 95% CI -2.1, 3.3), physical well-being (2.1; 95% CI -2.3, 6.5), and functional well-being (5.1; 95% CI 1.6, 8.6), but all 95% CIs were wide and most included zero. Recruitment feasibility and acceptability of the intervention were demonstrated, which suggest larger trials using an intensive nutrition intervention would be achievable.


Dual broadband near-infrared perfect absorber based on a hybrid plasmonic-photonic microstructure.
High performance light absorber with a broad bandwidth is particularly desirable for near-infrared photodetection and optical interconnects. Here we demonstrate a dual broadband perfect absorber in the near-infrared regime, which is based on a hybrid plasmonic-photonic microstructure. Such a microstructure is fabricated by self-assembling a monolayer colloidal crystal on an optically opaque metal film followed by depositing a thin metallic half-shell on the top of the colloidal particles. Both experimental and numerical simulation results show that the simply designed absorbers have dual broadband with absorption exceeding 90% in the near-infrared region with the absorption bands being scalable by tuning the size of the colloidal particles. Moreover, the absorption efficiency shows an extremely slight dispersion for the incident angles up to 50 degrees, benefit from the high symmetry as well as the highly modulated plasmonic microstructures that lead to a weak polarization dependence of these two absorption bands. The relative ease of growing high-quality colloidal crystals and the low cost of fabricating such plasmonic-photonic microstructures with high reproducibility could promise applicability of the light absorber in the field of photodetectors, thermal emitters and photovoltaics.


Comparison of the membrane proteome of virulent Mycobacterium tuberculosis and the attenuated Mycobacterium bovis BCG vaccine strain by label-free quantitative proteomics.
The Mycobacterium tuberculosis membrane is rich in antigens that are potential targets for diagnostics and the development of new vaccines. To better understand the mechanisms underlying MTB virulence and identify new targets for therapeutic intervention, we investigated the differential composition of membrane proteomes between virulent M. tuberculosis H37Rv (MTB) and the Mycobacterium bovis BCG vaccine strain. To compare the membrane proteomes, we used LC-MS/MS analysis in combination with label-free quantitative proteomics, utilizing the area under the curve of the extracted ion chromatograms of peptides obtained from m/z and retention time alignment of MS1 features. With this approach, we obtained relative abundance ratios for 2203 identified membrane-associated proteins in high confidence. Of these proteins, 294 showed statistically significant differences of at least two fold in relative abundance between MTB and BCG membrane fractions. Our comparative analysis detected several proteins associated with known genomic regions of difference between MTB and BCG as being absent, which validated the accuracy of our approach. In further support of our label-free quantitative data, we verified select protein differences by immunoblotting. To our knowledge, we have generated the first comprehensive and high-coverage profile of comparative membrane proteome changes between virulent MTB and its attenuated relative BCG, which helps elucidate the proteomic basis of the intrinsic virulence of the MTB pathogen.


Painting factor H onto mesenchymal stem cells protects the cells from complement- and neutrophil-mediated damage.
Mesenchymal stem cells (MSCs) are undergoing intensive testing in clinical trials as a promising new therapy for many inflammatory diseases and for regenerative medicine, but further optimization of current MSC-based therapies is required. In this study, we found that in addition to direct complement-mediated attack through the assembly of membrane attack complexes (MACs) that we and others have recently reported, of the released complement activation products, C5a, but not C3a, activates neutrophils in the blood to further damage MSCs through oxidative burst. In addition, we have developed a simple method for painting factor H, a native complement inhibitor, onto MSCs to locally inhibit complement activation on MSCs. MSCs painted with factor H are protected from both MAC- and neutrophil-mediated attack and are significantly more effective in inhibiting antigen-specific T cell responses than the mock-painted MSCs both in vitro and in vivo.


Interorganizational networks: using a theoretical model to predict effectiveness of rural health care delivery networks.
Interorganizational health care delivery networks have potential for sustaining health services delivery in rural areas faced with economic and demographic challenges. Four Nebraska rural health care delivery networks (Albion-Ord, Blue River Valley, Rural Partners, Inc., and Western Nebraska) were compared to an interorganizational model based on theories of interorganizational relations, exchange, population ecology, and synthesized collaboration. It assumes that outcomes, including effectiveness, are influenced by external and internal factors that are operationalized through external control, technology, structure, and operational process variables. Data were collected by a non-random, two-level cluster mail survey of network members (45/59 = 76.3% response rate). All networks received technical assistance from the Nebraska Office of Rural Health. Networks have formal organization, strategic plans, and official coordinators. Hospital administrators hold most leadership positions; few doctors or citizens are involved. Correlation and multiple regression analysis show partial fit between the research model and study networks. Effectiveness, measure by the gap between best possible and actual practice, increased with network connectivity (r=.36, p<.05), group methods of administrative decision-making (r=.52, p<.001) and sequential pattern of service delivery (r=.39, p<.05). Greater dependence on vertical funding corresponds to greater external control (r=.43, p<.01). The prediction that, as scope narrows, task intensity (r=.56, p<.001), duration (r=.41, p<.01), and task volume (r=.50, p<.01) increase is upheld. Centrality and network size decrease together (r=.43, p<.01) where there is little reliance on vertical sources of funds (r=.36, p<.05). The integrated interorganizational model demonstrates some efficacy for testing potential effectiveness of networks.


Video inpainting under constrained camera motion.
A framework for inpainting missing parts of a video sequence recorded with a moving or stationary camera is presented in this work. The region to be inpainted is general: it may be still or moving, in the background or in the foreground, it may occlude one object and be occluded by some other object. The algorithm consists of a simple preprocessing stage and two steps of video inpainting. In the preprocessing stage, we roughly segment each frame into foreground and background. We use this segmentation to build three image mosaics that help to produce time consistent results and also improve the performance of the algorithm by reducing the search space. In the first video inpainting step, we reconstruct moving objects in the foreground that are "occluded" by the region to be inpainted. To this end, we fill the gap as much as possible by copying information from the moving foreground in other frames, using a priority-based scheme. In the second step, we inpaint the remaining hole with the background. To accomplish this, we first align the frames and directly copy when possible. The remaining pixels are filled in by extending spatial texture synthesis techniques to the spatiotemporal domain. The proposed framework has several advantages over state-of-the-art algorithms that deal with similar types of data and constraints. It permits some camera motion, is simple to implement, fast, does not require statistical models of background nor foreground, works well in the presence of rich and cluttered backgrounds, and the results show that there is no visible blurring or motion artifacts. A number of real examples taken with a consumer hand-held camera are shown supporting these findings.


3D stereophotogrammetry quantitative lip analysis.
Reduction in lip volume is a stigmata of the aging face. There are many lip augmentation techniques but very few studies analyzing how these techniques change the three-dimensional structure of the lips. Furthermore, there is no consensus about whether the lip position should be standardized to either the lips closed or parted. The aim of this study was first to obtain a three-dimensional quantitative analysis of the lips in adults and to look for sexual dimorphism and, second, to compare whether more consistent measurements of the oral region can be obtained with the mouth open compared with it closed. Seventy young Caucasian volunteers underwent lip dimension analysis using 3D stereophotogrammetry with lips parted and closed. Parameters measured for consistency of results were linear distances (e.g., mouth width, total lip height, upper lip height), surface distances (e.g., upper vermilion), areas (e.g., vermilion upper and lower lip, total vermilion), and volumes (upper and lower lip volume, total lip volume). Analysis also compared lip dimensions between male and female subjects. Consistent and reproducible results were seen with the lips closed compared with lips apart. All lip parameters (distances, areas, and volumes) were larger in men than in women. The following measurements had significant differences between males and females: mouth width, upper lip height median, upper white lip height median, upper white lip height lateral, lower vermilion surface distance, and area of vermilion (p < 0.05). We present a novel technique for aesthetic assessment of the lips that is objective and achieves consistency with the lips in the closed position. Males have greater lip dimensions compared with females.


CREM: a master-switch in the transcriptional response to cAMP.
The CREM gene encodes both repressors and activators of cAMP-dependent transcription in a tissue and developmentally regulated manner. In addition, multiple and cooperative phosphorylation events regulate the function of the CREM proteins. CREM plays a key physiological and developmental role within the hypothalamic-pituitary axis. There is a functional switch in CREM expression during the development of male germ cells which is directed by the pituitary hormone FSH. The CREM protein in germ cells is a powerful activator which appears to function as a master-switch in the regulation of postmeiotic genes. CREM is inducible by activation of the cAMP signalling pathway with the kinetics of an early response gene. The induction is transient, cell-specific, does not involve increased transcript stability and does not require protein synthesis. The subsequent decline in CREM expression requires de novo protein synthesis. The induced transcript encodes ICER and is generated from an alternative, intronic promoter. ICER functions as a powerful repressor of cAMP-induced transcription, and represses the activity of its own promoter, thus constituting a negative autoregulatory loop.


Dissection of the APCCdh1-Skp2 cascade in breast cancer.
Skp2 is a subunit of the SCF ubiquitin protein ligase, which plays a vital role in the control of tumorigenesis via its regulation of G(1)-S transition. Deregulation of Skp2 in various types of cancers correlates with aggressive clinical behavior and poor prognosis. Recent studies suggest that cell cycle-dependent fluctuation of Skp2 is governed by APC(Cdh1), another important E3 ligase, thereby preventing premature entry into S phase. To assess the potential role of APC(Cdh1) in tumorigenesis through proteolysis of Skp2, we have dissected the APC(Cdh1)-Skp2 cascade. We manipulated the APC(Cdh1)-Skp2 cascade and examined its cellular behavior using both breast cancer and normal breast epithelial cells. Furthermore, applying immunohistochemistry, we analyzed the clinicopathologic significance of these molecules in patients with breast cancer. Analysis of tissue arrays indicated that the percentage of samples positive for Cdh1 in breast cancer was significantly lower compared with normal breast tissues (P=0.004). Conversely, the percentage of samples scored as positive for Skp2 in cancer was significantly higher than in normal tissues (P<0.001). Moreover, prognostic studies revealed that relatively high levels of Cdh1 are associated with survivability in patients with breast cancer. In addition, depletion of Cdh1 by small interfering RNA in normal breast cells resulted in increased cellular proliferation, whereas knockdown of Skp2 significantly suppressed growth in breast cancer cells. This study shows a correlation between Skp2 and APC(Cdh1) in breast cancer. Thus, Cdh1 may act as an important component in tumor suppression and could be considered as a novel biomarker in breast cancer.


Nanoparticle-Based Platform for Activatable Fluorescence Imaging and Photothermal Ablation of Endometriosis.
Endometriosis is a painful disorder where endometrium-like tissue forms lesions outside of the uterine cavity. Intraoperative identification and removal of these lesions are difficult. This study presents a nanoplatform that concurrently delineates and ablates endometriosis tissues using real-time near-infrared (NIR) fluorescence and photothermal therapy (PTT). The nanoplatform consists of a dye, silicon naphthalocyanine (SiNc), capable of both NIR fluorescence imaging and PTT, and a polymeric nanoparticle as a SiNc carrier to endometriosis tissue following systemic administration. To achieve high contrast during fluorescence imaging of endometriotic lesions, nanoparticles are constructed to be non-fluorescent prior to internalization by endometriosis cells. In vitro studies confirm that these nanoparticles activate the fluorescence signal following internalization in macaque endometrial stromal cells and ablate them by increasing cellular temperature to 53 ° C upon interaction with NIR light. To demonstrate in vivo efficiency of the nanoparticles, biopsies of endometrium and endometriosis from rhesus macaques are transplanted into immunodeficient mice. Imaging with the intraoperative Fluobeam 800 system reveals that 24 h following intravenous injection, nanoparticles efficiently accumulate in, and demarcate, endometriotic grafts with fluorescence. Finally, the nanoparticles increase the temperature of endometriotic grafts up to 47 °C upon exposure to NIR light, completely eradicating them after a single treatment.


Fairness in Music Recommender Systems: A Stakeholder-Centered Mini Review.
The performance of recommender systems highly impacts both music streaming platform users and the artists providing music. As fairness is a fundamental value of human life, there is increasing pressure for these algorithmic decision-making processes to be fair as well. However, many factors make recommender systems prone to biases, resulting in unfair outcomes. Furthermore, several stakeholders are involved, who may all have distinct needs requiring different fairness considerations. While there is an increasing interest in research on recommender system fairness in general, the music domain has received relatively little attention. This mini review, therefore, outlines current literature on music recommender system fairness from the perspective of each relevant stakeholder and the stakeholders combined. For instance, various works address gender fairness: one line of research compares differences in recommendation quality across user gender groups, and another line focuses on the imbalanced representation of artist gender in the recommendations. In addition to gender, popularity bias is frequently addressed; yet, primarily from the user perspective and rarely addressing how it impacts the representation of artists. Overall, this narrative literature review shows that the large majority of works analyze the current situation of fairness in music recommender systems, whereas only a few works propose approaches to improve it. This is, thus, a promising direction for future research.