Prospective audit of 200 patients undergoing laparoscopic inguinal hernia repair with follow-up from 1 to 4 years.
The results of 215 laparoscopic transabdominal pre-peritoneal inguinal hernia repairs are reported with a follow-up of 1-4 years (median 2.5 years). The patients" age range was 17-85 (median 59 years). Three recurrences occurred in the first 75 repairs, where a 12 x 7 cm mesh was used. There has been no recurrence in the subsequent 140 repairs where a larger 15 x 10 cm mesh was used for the repair. A total of 5% of patients developed urinary retention after the operation and a further 13% developed minor complications. The procedure was remarkably pain-free, with 25% requiring no analgesia after the operation and 67% requiring no analgesia after discharge from hospital. There was a rapid return to normal activity, with 55% driving within 1 week of the operation and 85% within 2 weeks. Sixty per cent returned to work within 2 weeks of the operation and 69% within 3 weeks. Forty-two of the patients had undergone a previous open hernia repair and 93% of these preferred the laparoscopic repair as there was less post-operative pain and a quicker recovery. The results show that laparoscopic hernia repair is remarkably pain-free, allows a rapid return to normal activity and has a low recurrence rate when a 15 x 10 cm mesh is used.


Predictors of Family Engagement in Child Post-Traumatic Stress Disorder Screening Following Exposure to Intimate Partner Violence.
Children's exposure to intimate partner violence (IPV) has numerous negative short- and long-term impacts on children's development, mental health, physical health, and adult functioning. While community-based organizations have an array of interventions aimed to increase survivor safety and prevent the development of, or treat post-traumatic stress disorder (PTSD), many families experiencing IPV never enter the doors of community-based organizations. To address this gap, there is an increasing number of partnerships between community-based organizations and first responders to increase support to families experiencing IPV. The Child Trauma Response Team (CTRT) is an innovative model that provides a coordinated, immediate, trauma-informed, and interdisciplinary response to families exposed to IPV. Given the lack of research on coordinated community interventions, the research questions for this study were as follows: (a) What are the family sociodemographic factors, crime factors, and program services most associated with family engagement in child PTSD screening following exposure to IPV? (b) What are the family sociodemographic factors and crime factors most associated with children screening positive for PTSD following exposure to IPV? The data for this study consist of 244 families with 352 children identified by the pilot CTRT. The results of this study suggest that a collaborative intervention designed to address caregiver and children's safety and well-being after a police-reported IPV incident is a promising model. Overall, more than 70% of children identified by the CTRT team completed a child PTSD screen, and 74.3% of children who completed the screens were screened positive for PTSD. The safety assessment service provided by the CTRT team was a predictor of the families' engagement in child PTSD screens. This is a critical finding and suggests the importance of developing program models that comprehensively address the needs of caregivers and children exposed to IPV.


Treatment delay and the risk of relapse in pediatric acute lymphoblastic leukemia.
Delays or interruptions in chemotherapy due to toxicity such as neutropenia or severe infections are common in the treatment of pediatric acute lymphoblastic leukemia (ALL). Based on the reports of worse outcomes in children with poorer compliance with therapy, there has been concern that toxicity-induced therapy interruptions could also compromise treatment outcome. In a retrospective study of treatment delays in our hospital between 2003 and 2013, the case notes of 141 patients were reviewed. The cumulative lengths of delays during the whole length of chemotherapy, during the intensive phase of treatment, and during maintenance treatment were analyzed. Within these categories, delays were split between less and more than the median value. The risk of relapse did not differ between patients with a longer or shorter delay during the total length of treatment or during the intensive phase. In addition, there was a trend when comparing patients above vs below the mean in length of treatment delays during maintenance, and there was a statistically significant difference in relapses when comparing patients in the lowest and highest quartiles of maintenance delays, with fewer relapses among those patients in the highest quartile for treatment delays.


Restriction fragment length polymorphism of the DNA of typhus group rickettsiae.
The DNA of 10 strains of Rickettsia prowazekii, 5 strains of Rickettsia typhi and 1 strain of Rickettsia canada was investigated by restriction fragment length polymorphism analysis. Interspecies differences were characterized by a great number of noncomigrating bands. Using the endonuclease HindIII and PstI fragments comigration as a quantitative criterion, genetic similarity coefficient was calculated for the pair Rickettsia prowazekii/Rickettsia typhi-32.0%, for Rickettsia prowazekii/Rickettsia canada-22.7%, and for Rickettsia typhi/Rickettsia canada-23.5%. Intraspecies differences expressed are very subtle and concern 1-2 noncomigrating fragments. The investigated strains of Rickettsia prowazekii and Rickettsia typhi can be divided into 2 groups without any correlation to the source and period of isolation, or to strain passage history.


Time-resolved fluorescence resonance energy transfer: a versatile tool for the analysis of nucleic acids.
The biological functions of nucleic acids in processes of DNA replication, transcription, homologous recombination, mRNA translation, and ribozyme catalysis are intimately linked to their three-dimensional structures and to conformational changes induced by proteins, metal ions and other ligands. Fluorescence spectroscopy is a powerful technique for probing the structure and conformational dynamics of biological macromolecules under a wide range of solution conditions. Fluorescence resonance energy transfer (FRET) provides long-range distance information from 10 to 100 A, a range that is useful for probing the global structure of nucleic acids. While steady-state measurements of FRET provide the average distance between donor and acceptor, much more information is available from the analysis of the nanosecond emission decay of the donor in time-resolved FRET (trFRET) experiments. Analysis of the decay in terms of donor-acceptor distance distributions can resolve different conformers in a heterogeneous mixture, providing information on the global structure and flexibility of each species as well as their equilibrium populations. In this review, we outline the principles of trFRET and the methods used to incorporate fluorescent probes into DNA and RNA. Examples of specific applications are presented to illustrate the versatility of trFRET as a tool to define global structures, to identify conformational heterogeneity and flexibility, to investigate the energetics of tertiary structure formation and to probe structural rearrangements of nucleic acids.


A novel approach to assessing the ecosystem-wide impacts of reintroductions.
Reintroducing a species to an ecosystem can have significant impacts on the recipient ecological community. Although reintroductions can have striking and positive outcomes, they also carry risks; many well-intentioned conservation actions have had surprising and unsatisfactory outcomes. A range of network-based mathematical methods has been developed to make quantitative predictions of how communities will respond to management interventions. These methods are based on the limited knowledge of which species interact with each other and in what way. However, expert knowledge isn't perfect and can only take models so far. Fortunately, other types of data, such as abundance time series, is often available, but, to date, no quantitative method exists to integrate these various data types into these models, allowing more precise ecosystem-wide predictions. In this paper, we develop mathematical methods that combine time-series data of multiple species with knowledge of species interactions and we apply it to proposed reintroductions at Booderee National Park in Australia. There have been large fluctuations in species abundances at Booderee National Park in recent history, following intense feral fox (Vulpes vulpes) control, including the local extinction of the greater glider (Petauroides volans). These fluctuations can provide information about the system isn't readily obtained from a stable system, and we use them to inform models that we then use to predict potential outcomes of eastern quoll (Dasyurus viverrinus) and long-nosed potoroo (Potorous tridactylus) reintroductions. One of the key species of conservation concern in the park is the Eastern Bristlebird (Dasyornis brachypterus), and we find that long-nosed potoroo introduction would have very little impact on the Eastern Bristlebird population, while the eastern quoll introduction increased the likelihood of Eastern Bristlebird decline, although that depends on the strength and form of any possible interaction.


Profile-based retrieval of records in medical databases.
Ontologies establish relationships between different terms, yet their potential in querying has not yet been fully realized. In this paper, we study the problem of ontology-supported profile-based retrieval of medical records. We present an algorithm that provides two independent techniques (used in isolation or in unison) to address the shortcomings of existing keyword-based retrieval solutions, and provide an implementation and experiments to illustrate the merits of our approach.


TLE lateralization using whole brain structural connectivity.
A prerequisite of temporal lobe epilepsy (TLE) surgery is to lateralize the disease. Recent studies have shown the capability of diffusion weighted MRI (DWMRI) in lateralizing TLE patients. This has been achieved by analyzing diffusion parameters of specific white matter tracts or regions known to be involved in the disease; however, other brain regions and connections have not been investigated for TLE lateralization. Whole brain structural connectivity using DWMRI provides a wealth of information regarding the structural connections in the brain. This information can be explored to find the most effective connections for TLE lateralization. In this work, we investigate the connectivity matrices calculated from DWMRI of 10 left and 10 right TLE patients to find the most effective connections for lateralizing the disease. Linear support vector machine (LSVM) classifier and leave-one-out cross validation scheme are used to estimate classification performance of the connectivity feature subsets. A subset of three connections with 100% classification accuracy is found. The corresponding LSVM classifier may be used to lateralize prospective TLE patients.


Vestibular Schwannoma Presenting with Bilateral Papilledema Without Hydrocephalus: Case Study.
Bilateral papilledema secondary to obstructive or communicating hydrocephalus in patients with vestibular schwannomas is a known presentation; however, papilledema in the absence of hydrocephalus is rarely reported and its mechanism is poorly understood. We report a case of a 20-year-old woman presenting with visual deterioration and bilateral papilledema on fundoscopy. Magnetic resonance imaging (MRI) revealed a giant vestibular schwannoma with no sign of hydrocephalus. The only imaging evidence of increased pressure on preoperative imaging studies was seen on a T2-weighted MRI, where there was subtle dilatation of the arachnoid space of the optic sleeve. We presume that this patient developed papilledema by some mechanism not connected to hydrocephalus. In a young patient, papilledema may be a sign preceding hydrocephalus, or she may have had pseudotumor cerebri concomitant with her vestibular schwannoma. In either case, removal of the vestibular schwannoma solved the problem. She had complete visual recovery, irrespective of the mechanism.


Development of a Ferroptosis-Related lncRNA Signature to Predict the Prognosis and Immune Landscape of Bladder Cancer.
The tight relationship between ferroptotic cell death and immune response demonstrated by recent studies enlightened us to detect the underlying roles of ferroptosis-related long noncoding RNAs (frlncRNAs) in the tumor microenvironment of bladder cancer (BCa). We collected 121 ferroptosis regulators from previous studies. Based on their expression values, 408 cases with BCa were clustered. The patients in different clusters showed diverse immune infiltration, immunotherapy response, and chemotherapy effectiveness, revalidating the tight correlation with ferroptosis and tumor immunity. Through differential, coexpression, Kaplan-Meier, Lasso, and Cox analysis, we developed a 22-lncRNA-pair signature to predict the prognosis of BCa based on gene-pair strategy, where there is no need for definite expression values. The areas under the curves are all over 0.8. The risk model also helped to predict immune infiltration, immunotherapeutic outcomes, and chemotherapy sensitivity. Totally, the prognostic assessment model indicated a promising predictive value, also providing clues for the interaction between ferroptosis and BCa immunity.


Sling operation for recurrent stress incontinence using the tendon of the palmaris longus.
A sling procedure is described for recurrent stress incontinence in women who had been previously treated, unsuccessfully, by one or more surgical interventions. The procedure consists of combining a vaginal Kelly urethral plication with a sling prosthesis, using the tendon of the palmaris longus. The former will correct the bladder neck funneling while the latter will restore its position to a high retropubic point, in a hammock suspended from Cooper's ligament. The palmaris longus is one of the superficial groups of flexors. Its advantages are in the tendon's availability, its location for accessibility, its relative ease of removal, and the fact that it is functionally nonessential. Six patients have been treated with this technique with excellent results after one to three years of follow-up.


Health-related quality of life of young women with breast cancer. Review of the literature.
The purpose of the present article was to investigate the health related quality of life (QoL) of young women with breast cancer. For the purposes of this article, we reviewed the literature via the electronic databases Pubmed, Scopus and Google Scholar. Key words used were breast cancer, young women, health related quality of life, and quality of life. Young women reported fatigue, pain in the breast and hand problems with lymphedema as the most frequent physical effects of treatment. Other physical problems were the not periodic and painful menses, vaginal dryness and loss of libido. Many young women had depressive symptoms such as depressed mood, helplessness, hopelessness, sleep loss, psychomotor retardation and disorders of appetite. There were often concerns about the health monitoring and self-image, while they were anxious if they will have a baby in the future or if they can nurture the existing ones. Many problems arose in the career of young women. They faced discrimination in the labor supply and/or layoff because they were considered unable to do their job effectively. In addition, they reported isolation problems and feeling different from other women of similar age. Young women consider that their healthrelated QoL is worse compared with older women. Young women worry about their future, with particular reference to their role as mothers and especially to children-bearing. The free screening and non-exclusion of young women is particularly important for breast cancer prevention and women's well-being.


Efficacy of high-intensity laser therapy in subacromial impingement syndrome: a three-month follow-up controlled clinical trial.
To evaluate the effectiveness of high-intensity laser therapy on shoulder pain and function in subacromial impingement syndrome. Clinical controlled trial with alternate allocation. Hospital Department of Rehabilitation. A total of 46 participants with subacromial impingement syndrome. Participants were sequence allocated to an intervention group (high-intensity laser therapy + exercise therapy) and control group (sham-laser + exercise therapy) and received 15 sessions (five days a week during three weeks). Patiens were evaluated at baseline, after 15 sessions, and at one month and at three months after completing the intervention. The main outcome variables were pain and functionality as measured by visual analogue scale; pressure pain threshold; Shoulder Pain and Disability Index; Constant-Murley Score; and QuickDASH. Secondary outcomes were number of sessions at discharge and drug use. A total of 21 patients in high-intensity laser therapy group (56.7 ± 8.9 years) and 22 patients in sham-laser group (61.3 ± 8.9 years) concluded the study. Visual analogue scale (cm) at baseline, one-month, and three-months were 6.2 ± 0.5, 3 ± 2.6, and 2.6 ± 2.4 for the control group and 5.4 ± 1.5, 3.6 ± 1.3, and 1.8 ± 1.7 for experimental group, respectively. Shoulder Pain and Disability Index (points) at baseline, one-month, and three-monts were 51.8 ± 16.1, 16.3 ± 16.1, and 13.6 ± 17.1 in the control group and 41.8 ± 20.6, 20.5 ± 19.7, 11 ± 14.5 in experimental group, respectively. No differences were found between groups ( P > 0.05). The effect of high-intensity laser therapy plus exercise is not higher than exercise alone to reduce pain and improve functionality in patients with subacromial syndrome.


Determination of the ideal sampling technique to reduce repeated procedures:a comparative study including 393 fine-needle aspirations for thyroid nodules.
Fine-needle aspiration biopsy is an established method for the evaluation of thyroid nodules, but it has not been standardized worldwide yet. Adequacy of the aspirations is affected by several factors. The aim of this study is to determine the main factors affecting the adequacy and to suggest a procedural technique expected to reduce repeated procedures. A total of 393 aspiration procedures performed using either 22-gauge or 27-gauge needles were included in the study. The samplings were classified as inadequate or adequate according to the cytopathological reports, and results were compared. The rate of adequate samplings was higher in the 27-gauge group and the difference was statistically significant. Neither the size of nodules nor the number of slides used for smearing affected the adequacy. There was not a statistically significant relation between the needle size and the nodule size or the number of slides in terms of adequacy. Needle size is an important factor that affects the adequacy of samplings. The nodule size and the number of slides do not affect the adequacy. However, bloody and thicker smears are difficult for pathologists to evaluate and result in inadequacy.


Interphase Engineering Enhanced Electro-chemical Stability of Prelithiated Anode.
Prelithiation is an essential technology to compensate for the initial lithium loss of lithium-ion batteries due to the formation of solid electrolyte interphase (SEI) and irreversible structure change. However, the prelithiated materials/electrodes become more reactive with air and electrolyte resulting in unwanted side reactions and contaminations, which makes it difficult for the practical application of prelithiation technology. To address this problem, herein, interphase engineering through a simple solution treatment after chemical prelithiation is proposed to protect the prelithiated electrode. The used solutions are carefully selected, and the composition and nanostructure of the as-formed artificial SEIs are revealed by cryogenic electron microscopy and X-ray photoelectron spectroscopy. The electrochemical evaluation demonstrates the unique merits of this artificial SEI, especially for the fluorinated interphase, which not only enhances the interfacial ion transport but also increases the tolerance of the prelithiated electrode to the air. The treated graphite electrode shows an initial Coulombic efficiency of 129.4%, a high capacity of 170 mAh g-1 at 3 C, and negligible capacity decay after 200 cycles at 1 C. These findings not only provide a facile, universal, and controllable method to construct an artificial SEI but also enlighten the upgrade of battery fabrication and the alternative use of advanced electrolytes.


The interplay of meaning, sound, and syntax in sentence production.
A discussion of modularity in language production processes, with special emphasis on processes for retrieving words and building syntactic structures for a to-be-uttered sentence, is presented. The authors' 1st goal was to assess the extent to which information processing is encapsulated between different processing stages. In particular, they assessed whether the input from one processing stage to the next is minimal and whether the flow of information in the system is strictly unidirectional. On the basis of the reviewed evidence, they conclude that both assumptions have to be revised. Their 2nd goal was to propose an altemative framework that does not assume strict encapsulation but that maintains multiple levels of integration for production.


Applications of nanomaterials in anti-VEGF treatment for ophthalmic diseases.
Angiogenesis has been determined to be essential in the occurrence and metastasis of diabetic retinopathy (DR), age-related macular degeneration (AMD), retinal vein occlusion (RVO), choroidal neovascularization (CNV), retinopathy of prematurity (ROP), tumor, etc. However, the clinical use of anti-vascular endothelial growth factors (VEGF) drugs is currently limited due to its high cost, potential side effects, and need for repeated injections. In recent years, nanotechnology has shown promising results in inhibiting neovascularization and reducing reactive oxygen species (ROS) or inflammatory factors. Some nanomaterials can also act as vehicles for drug delivery, such as lipid nanoparticles and PLGA. The process of angiogenesis and its molecular mechanism are discussed in this article. At the same time, this study aims to systematically review the research progress of nanotechnology and offer more treatment options for neovascularization-related diseases in clinical ophthalmology.


Basic gross motor assessment. Tool for use with children having minor motor dysfunction.
Children with minor motor problems are often referred for evaluation of these problems to physical therapists who work in educational environments. Measures that therapists use to assess seriously disabled children are often inappropriate for these children. The Basic Gross Motor Assessment was developed after analyzing research on minor motor dysfunction. Standard procedures were outlined and a sample of 1,260 randomly selected children aged 5 years 6 months to 12 years 5 months served for norming purposes. Validity and reliability studies were completed with an additional 285 subjects. The Basic Gross Motor Assessment is presented as a useful tool for evaluating minor motor problems in children and identifying those children who require further physical therapy assessment and perhaps direct treatment.


Reconsideration of Xysticus species described by Ehrenfried Schenkel from Mongolia and China in 1963 (Araneae: Thomisidae).
The types of nine Xysticus species described by Schenkel (1963) from China and Mongolia are revised. Comments on all 16 species described by Schenkel in 1963 are provided. Three species are synonymised with Xysticus davidi Schenkel, 1963: X. excavatus Schenkel, 1963, syn. n., X. hotingchiehi Schenkel, 1963, syn. n., X. pentagonius Seyfulina & Mikhailov, 2004, syn. n. Xysticus fagei Schenkel 1963, syn. n. is a junior synonym of X. ephippiatus Simon, 1880. Xysticus lesserti Schenkel, 1963 is revalidated and removed from synonymy with X. kurilensis Strand, 1907. A male specimen from Gansu identified by Schenkel as Xysticus sibiricus Kulczyński, 1908 is described as a new species X. courti sp. n.


Second serogroup of Legionella quinlivanii isolated from two unrelated sources in the United Kingdom.
A series of strains, presumptively identified as legionellas on the basis of their nutritional requirements and biochemical reactivity, were isolated from two unrelated environmental sources in the UK. Representatives of each of these series had a restriction endonuclease digest pattern indistinguishable from that of the Legionella quinlivanii type strain (1442-AUS-E) and the identity of these strains was confirmed by DNA homology studies. Serological examination of the two strains showed that they were distinct from the type strain 1442-AUS-E but indistinguishable from each other. A second serogroup, L. quinlivanii serogroup 2 (type strain LC870; NCTC 12434), is proposed to accommodate these strains.


Maternal outcome of selective feticide due to fetal anomaly in late trimester: A retrospective 10 years' experience in Taiwan.
Feticide was suggested to avoid delivering children with abnormalities. Recently, twin pregnancies have increased. Selective feticide was proposed to achieve a good outcome of pregnancy. This study aimed to evaluate the performance of feticide in twin pregnancy with fetal anomaly. This was a retrospective study enrolled from 2009 to 2018. A total of 68 pregnancies with fetal anomalies received feticide. Potassium chloride was injected into the left ventricle to induce fetal asystole. Maternal and fetal characteristics of 16 dichorionic twins were documented to compare before and after 24th gestational week. All pregnant women received feticide without any maternal or fetal complication. The reasons for choosing feticide were divided into four groups, including morphologic defect (61.8%), genetic-chromosomal abnormality (30.9%), obstetrical complication (5.9%), and maternal request (1.5%). Mean gestational age at delivery was significantly higher in dichorionic twins who underwent selective feticide before than after 24th gestational week (36.7 vs 33.4, p = 0.04). Intracardiac injection of potassium chloride was effective for feticide and safe for mothers and fetuses. Selective feticide served as an alternative approach for twin pregnancy with fetal anomaly after sufficient discussion.


EATING BEHAVIOR IN RESPONSE TO ACUTE STRESS.
Obesity is a medical and social problem with a dramatically increasing prevalence. It is important to take action since childhood to prevent and treat obesity and metabolic syndrome. Infantile obesity affects all body systems starting in childhood and continuing to adulthood. Understanding the impact of stressors on weight status may be especially important for preventing obesity. The relationship between stress, eating behavior and obesity is not fully understood. However, there is evidence that stress causes disorders in hypothalamic-pituitary-adrenal (HPA) axis, system that regulates both stress and feeding responses. Also, the response is different depending on the type of stressors. Chronic stress, especially when people live in a palatable food environment, induces HPA stimulation, excess glucocorticoids, insulin resistance, which lead to inhibition of lipid mobilization, accumulation of triglyceride and retention of abdominal fat.


Balance training using an iPhone application in people with familial dysautonomia: three case reports.
Familial dysautonomia (FD) is a rare genetic autosomal recessive disease that impairs vital functions and causes neural and motor deficiency. These motor deficits often are characterized by static and dynamic instability and an ataxic gait. As a result, people with FD are at risk for significant physical impairment and falls and pose unique challenges for delivering rehabilitation exercise. Consequently, there is a need for challenging ways to safely and feasibly deliver active exercise rehabilitation to these individuals. This case report describes 3 people with FD (ages 11, 12, and 22 years) with gait and stability problems who attended rehabilitation exercises augmented by the use of an iPhone application specifically developed for the program. The Berg Balance Scale and the Four Square Step Test were conducted prior to training, after training, and after 2 months of follow-up without training. Two patients showed improvements on both measures at the posttest, which were maintained throughout follow-up testing. Although greater experience is needed to more fully evaluate the efficiency of the iPhone application used in this program for people with FD, the results of these initial cases are encouraging. Systematically and prospectively tracking motor abilities and other functional outcomes during rehabilitation of individuals with FD who use the suggested application in balance training is recommended in order to provide greater evidence in this area.


Proteins specified by herpes simplex virus. VI. Viral proteins in the plasma membrane.
Previous papers in the series have shown that the surface membranes of herpesvirus-infected cells acquire new immunological specificities and that purified infected cell membrane preparations, characterized by their physical properties rather than topology in the cell, contain new glycoproteins genetically determined by the virus. In this study, we prepared purified plasma membrane identified by its 5' nucleotidase, fucose, and reduced nicotinamide adenine dinucleotide-diaphorase content. Analysis of the membrane proteins and glycoproteins by electrophoresis in acrylamide gels indicated the following. (i) Purified plasma membranes from infected cells contained two sets of proteins, i.e., host proteins were present both before and after infection and viral proteins were present only after infection. (ii) After infection, no appreciable selective or nonselective loss of host proteins from membranes was demonstrable. However, no new host proteins were made. (iii) Electropherograms of plasma membrane proteins from infected cells indicated the presence of at least 12 virus-specific proteins ranging in molecular weight from 25 x 10(3) to 126 x 10(3) daltons. Of these, at least nine were glycosylated. Proteins and glycoproteins with similar electrophoretic mobilities but in somewhat different ratios were also present in preparations of highly purified virions.


Evaluation of sorption-desorption processes for metalaxyl in natural and artificial soils.
The main process controlling soil-pesticide interaction is the sorption-desorption as influenced by active soil surfaces. The sorption phenomena can influence translocation, volatility, persistence and bioactivity of a pesticide in soil. The present investigation was conducted on natural and artificial soils in order to enumerate the effect of soil components such as montmorillonite and ferrihydrite on the sorption behaviour of the fungicide metalaxyl and if sorption-desorption of the chiral pesticide affects the enantiomeric ratio. The sorption-desorption characteristics of metalaxyl were investigated by batch equilibration technique in a natural soil, two artificial soils, and in pure montmorillonite and ferrihydrite. After extraction, pesticide residues were analyzed by conventional and chiral chromatography using tandem mass spectrometry. A KdSorp (2.3-6.5) suggests low level sorption of metalaxyl with an appreciable risk of run-off and leaching. Thus, metalaxyl poses a threat to surface and ground water contamination. Furthermore, desorption tests revealed a hysteretic effect (H ≤ 0.8) in natural and artificial soils. Significant amount of metalaxyl was found tightly bound to the adsorbents without desorbing readily after desorption cycle. Desorption of 22-56% of the total amount of the retained metalaxyl was determined. This study reveals that an artificial soil derived from different soil constituents can be used to assess their influence on sorption/desorption processes. The present investigation showed that both montmorillonite and ferrihydrite play a significant role in the sorption of metalaxyl. The sorption doesn't influence the enantiomeric ratio of racemic metalaxyl.


Elementary Protein Analysis in Schizosaccharomyces pombe.
Biochemical monitoring and interrogation of protein function is a critical component of most fission yeast studies. In particular, its small proteome size, high conservation of core molecular cell biology, and genetic malleability make Schizosaccharomyces pombe an excellent model organism in which to use mass spectrometry to conduct proteome-wide approaches. Here we discuss issues encountered during the analysis of fission yeast protein preparations.


Urbanization and child growth in Nepal.
The growth of children (0-60 months) of rural-to-urban migrant women was studied in a population of carpet-making workers in a peri-urban community of Kathmandu, Nepal. Mean height-for-age (HAZ) and weight-for-age (WAZ) z-scores are compared for two groups of children belonging to recent urban migrant women (resident <5 years) and to long-term migrants (resident ⩾5 years). The process of urbanization and adaptation to the city environment was explored by examining cohort differences in health care utilization, diarrheal morbidity, breastfeeding practices, demographic, and socioeconomic characteristics. On average, both children of recent and long-term migrants have moderate-to-severe linear growth retardation after 12 months of age. There is, however, a statistically significant difference in mean HAZ and WAZ scores between children depending on maternal length of urban residence status; children of long-term migrants have better growth status compared to children of recent migrants. Nevertheless, there are no significant differences between long-term and recent migrant families in terms of socioeconomic characteristics and selected biobehavioral practices which have been associated with modernization and adaptation to an urban environment. It is concluded that the process of adaptation to an urban environment cannot be explained by standard biobehavioral indicators of modernization and requires further consideration. Am. J Hum. Biol. 10:307-315, 1998. © 1998 Wiley-Liss, Inc.


Adverse Reactions to Biologic Therapy.
Biologic therapies are emerging as a significant therapeutic option for many with debilitating inflammatory and autoimmune conditions. As expansion in the number of FDA-approved agents continue to be seen, more unanticipated adverse reactions are likely to occur. Currently, the diagnostic tools, including skin testing and in vitro testing, to evaluate for immediate hypersensitivity reactions are insufficient. In this review, management strategies for common acute infusion reactions, injection site reactions, and immediate reactions suggestive of IgE-mediated mechanisms are discussed. Desensitization can be considered for reactions suggestive of IgE-mediated mechanisms, but allergists/immunologists should be involved in managing these patients.


Differences in number and distribution of striatal calbindin medium spiny neurons between a vocal-learner (Melopsittacus undulatus) and a non-vocal learner bird (Colinus virginianus).
Striatal projecting neurons, known as medium spiny neurons (MSNs), segregate into two compartments called matrix and striosome in the mammalian striatum. The matrix domain is characterized by the presence of calbindin immunopositive (CB+) MSNs, not observed in the striosome subdivision. The existence of a similar CB+ MSN population has recently been described in two striatal structures in male zebra finch (a vocal learner bird): the striatal capsule and the Area X, a nucleus implicated in song learning. Female zebra finches show a similar pattern of CB+ MSNs than males in the developing striatum but loose these cells in juveniles and adult stages. In the present work we analyzed the existence and allocation of CB+ MSNs in the striatal domain of the vocal learner bird budgerigar (representative of psittaciformes order) and the non-vocal learner bird quail (representative of galliformes order). We studied the co-localization of CB protein with FoxP1, a transcription factor expressed in vertebrate striatal MSNs. We observed CB+ MSNs in the medial striatal domain of adult male and female budgerigars, although this cell type was missing in the potentially homologous nucleus for Area X in budgerigar. In quail, we observed CB+ cells in the striatal domain at developmental and adult stages but they did not co-localize with the MSN marker FoxP1. We also described the existence of the CB+ striatal capsule in budgerigar and quail and compared these results with the CB+ striatal capsule observed in juvenile zebra finches. Together, these results point out important differences in CB+ MSN distribution between two representative species of vocal learner and non-vocal learner avian orders (respectively the budgerigar and the quail), but also between close vocal learner bird families.


DREF plays multiple roles during Drosophila development.
DREF was originally identified as a transcription factor that coordinately regulates the expression of DNA replication- and proliferation-related genes in Drosophila. Subsequent studies demonstrated that DREF is involved in tumor suppressor pathways including p53 and Hippo signaling. DREF also regulates the expression of genes encoding components of the JNK and EGFR pathways during Drosophila development. DREF itself is under the control of the TOR pathway during cell and tissue growth responding to nutrition. Recent studies revealed that DREF plays a role in chromatin organization including insulator function, chromatin remodeling, and telomere maintenance. DREF is also involved in the regulation of genes related to mitochondrial biogenesis, linking it to cellular proliferation. Thus, DREF is now emerging as not only a transcription factor, but also a multi-functional protein. In this review, we summarize current advances in studies on the novel functions of Drosophila DREF.


Integrative analysis of copy number and gene expression in breast cancer using formalin-fixed paraffin-embedded core biopsy tissue: a feasibility study.
An absence of reliable molecular markers has hampered individualised breast cancer treatments, and a major limitation for translational research is the lack of fresh tissue. There are, however, abundant banks of formalin-fixed paraffin-embedded (FFPE) tissue. This study evaluated two platforms available for the analysis of DNA copy number and gene expression using FFPE samples. The cDNA-mediated annealing, selection, extension, and ligation assay (DASL™) has been developed for gene expression analysis and the Molecular Inversion Probes assay (Oncoscan™), were used for copy number analysis using FFPE tissues. Gene expression and copy number were evaluated in core-biopsy samples from patients with breast cancer undergoing neoadjuvant chemotherapy (NAC). Forty-three core-biopsies were evaluated and characteristic copy number changes in breast cancers, gains in 1q, 8q, 11q, 17q and 20q and losses in 6q, 8p, 13q and 16q, were confirmed. Regions that frequently exhibited gains in tumours showing a pathological complete response (pCR) to NAC were 1q (55%), 8q (40%) and 17q (40%), whereas 11q11 (37%) gain was the most frequent change in non-pCR tumours. Gains associated with poor survival were 11q13 (62%), 8q24 (54%) and 20q (47%). Gene expression assessed by DASL correlated with immunohistochemistry (IHC) analysis for oestrogen receptor (ER) [area under the curve (AUC) = 0.95], progesterone receptor (PR)(AUC = 0.90) and human epidermal growth factor type-2 receptor (HER-2) (AUC = 0.96). Differential expression analysis between ER+ and ER- cancers identified over-expression of TTF1, LAF-4 and C-MYB (p ≤ 0.05), and between pCR vs non-pCRs, over-expression of CXCL9, AREG, B-MYB and under-expression of ABCG2. This study was an integrative analysis of copy number and gene expression using FFPE core biopsies and showed that molecular marker data from FFPE tissues were consistent with those in previous studies using fresh-frozen samples. FFPE tissue can provide reliable information and will be a useful tool in molecular marker studies. Trial registration number ISRCTN09184069 and registered retrospectively on 02/06/2010.


Childhood maltreatment and DSM-IV adult mental disorders: comparison of prospective and retrospective findings.
Prior research reports stronger associations between childhood maltreatment and adult psychopathology when maltreatment is assessed retrospectively compared with prospectively, casting doubt on the mental health risk conferred by maltreatment and on the validity of retrospective reports. To investigate associations of psychopathology with prospective v. retrospective maltreatment ascertainment. A nationally representative sample of respondents aged 16-27 years (n = 1413) in New Zealand completed a retrospective assessment of maltreatment and DSM-IV mental disorders. Survey data were linked with a national child protection database to identify respondents with maltreatment records (prospective ascertainment). Childhood maltreatment was associated with elevated odds of mood, anxiety and drug disorders (odds ratios = 2.1-4.1), with no difference in association strength between prospective and retrospective groups. Prospectively ascertained maltreatment predicted unfavourable depression course involving early onset, chronicity and impairment. Prospectively and retrospectively assessed maltreatment elevated the risk of psychopathology to a similar degree. Prospectively ascertained maltreatment predicted a more unfavourable depression course.


Cosmological solutions in macroscopic gravity.
In the macroscopic gravity approach to the averaging problem in cosmology, the Einstein field equations on cosmological scales are modified by appropriate gravitational correlation terms. We present exact cosmological solutions to the equations of macroscopic gravity for a spatially homogeneous and isotropic macroscopic space-time and find that the correlation tensor is of the form of a spatial curvature term. We briefly discuss the physical consequences of these results.


Single-stage revision for peri-prosthetic shoulder infection: outcomes and results.
There have been only a few small studies of patients with an infected shoulder replacement treated with a single-stage exchange procedure. We retrospectively reviewed 35 patients (19 men and 16 women) with a peri-prosthetic infection of the shoulder who were treated in this way. A total of 26 were available for clinical examination; three had died, two were lost to follow-up and four patients had undergone revision surgery. The mean follow-up time was 4.7 years (1.1 to 13.25), with an infection-free survival of 94%. The organisms most commonly isolated intra-operatively were Staphylococcus epidermidis and Propionibacterium acnes; two patients developed a recurrent infection. Three different types of prosthesis were used: a hemiarthroplasty, a hemiarthroplasty with a bipolar head and reverse prosthesis. The mean Constant-Murley score at final follow-up was 43.3 (14 to 90) for patients with a hemiarthroplasty, 56 (40 to 88) for those with a hemiarthroplasty with a bipolar head and 61 (7 to 90) for those with a reverse prosthesis. The mean hospital stay was 10.6 days (5 to 29). Single-stage exchange is a successful and practical treatment for patients with peri-prosthetic infection of the shoulder.


[Pulmonary vascular endothelial cell growth and PPARgamma].
PPARgamma is a member of a family of nuclear receptors/ligand-dependent transcription factors, which bind to hormone response elements on target gene promoters. An antiproliferative and proapoptotic action profile of PPARgamma has been described, but little is known about the role of PPARgamma in vascular remodeling. We reported a reduced PPARgamma gene and protein expression in the lungs from patients with severe pulmonary hypertension and loss of PPARgamma expression in their complex vascular lesion. We showed that fluid shear stress reduces PPARgamma expression in ECV304 endothelial cells and that ECV304 cells that stably express dominant-negative PPARgamma form lumen-obliterating lung vascular lesion in the artificial capillaries under fluid shear stress and in the intrapulmonary arteries after tail vein injection in nude mice. Recently, there are some evidences that PPARgamma may represent a novel therapeutic target in pulmonary hypertension.


Contemporary prevalence and predictors of anxiety among patients living with HIV/AIDS in Ghana.
To identify the prevalence and associated factors of anxiety in people living with HIV/AIDS in a tertiary centre in Ghana. The study employed a cross-sectional design. The study was conducted in the outpatient HIV clinic of a tertiary hospital. Participants were adult PLWHA receiving OPD care, including those established on combined antiretroviral therapy (cART) and newer patients who were not on cART. Four hundred ninety-five participants aged ≥30 years were consecutively enrolled on the study. Demographic and clinical data were collected using standard questionnaires and patient files. Anxiety was assessed using the Hospital Anxiety and Depression Scale (HADS). Multivariate logistic regression analysis was done to identify associated factors. Proportion of PLWHA who had HADS score of ≥8. Overall prevalence of anxiety was 61.0% (95%CI: 56.6 - 65.3), with no significant difference between recently diagnosed (≤ 6 months, 64.3%) and those with established diagnoses (>6 months, 59.1%). Urban residence (aOR: 1.67, 95%CI: 1.12 - 2.51), alcohol use (aOR: 1.64, 95%CI: 1.13 - 2.38) and depression (aOR: 13.62, 95%CI: 7.91 - 23.45) were independently associated with anxiety. In this sample, 6 in 10 Ghanaian PLWHA had evidence of anxiety. Liaison with the national mental health service for more comprehensive and integrated care and further research into the mental health of PLWHA is recommended to reduce this high burden of anxiety. This study was funded by a grant from the National Institutes of Health Fogarty International Center (R21 TW010479).


A Focus on Triazolium as a Multipurpose Molecular Station for pH-Sensitive Interlocked Crown-Ether-Based Molecular Machines.
The control of motion of one element with respect to others in an interlocked architecture allows for different co-conformational states of a molecule. This can result in variations of physical or chemical properties. The increase of knowledge in the field of molecular interactions led to the design, the synthesis, and the study of various systems of molecular machinery in a wide range of interlocked architectures. In this field, the discovery of new molecular stations for macrocycles is an attractive way to conceive original molecular machines. In the very recent past, the triazolium moiety proved to interact with crown ethers in interlocked molecules, so that it could be used as an ideal molecular station. It also served as a molecular barrier in order to lock interlaced structures or to compartmentalize interlocked molecular machines. This review describes the recently reported examples of pH-sensitive triazolium-containing molecular machines and their peculiar features.


A Framework of Composite Functional Gradient Methods for Generative Adversarial Models.
Generative adversarial networks (GAN) are trained through a minimax game between a generator and a discriminator to generate data that mimics observations. While being widely used, GAN training is known to be empirically unstable. This paper presents a new theory for generative adversarial methods that does not rely on the traditional minimax formulation. Our theory shows that with a strong discriminator, a good generator can be obtained by composite functional gradient learning, so that several distance measures (including the KL divergence and the JS divergence) between the probability distributions of real data and generated data are simultaneously improved after each functional gradient step until converging to zero. This new point of view leads to stable procedures for training generative models. It also gives a new theoretical insight into the original GAN. Empirical results on image generation show the effectiveness of our new method.


Prediction of Tensile Behavior of UHSFRC Considering the Flow Field in the Placing Dominated by Shear Flow.
Considering the case of fabricating a UHSFRC (ultra-high strength fiber-reinforced concrete) beam with the method of one end placing and self-flowing to the other end, it was intended to simulate the variation of the fiber orientation distribution according to the flow distance and the variation of the resultant tensile behaviors. Then the validity of the simulation approach was shown by comparing the simulated results with experimental ones. A three-point bending test with a notched beam was adopted for the experiment and a finite element analysis was performed to obtain the simulated results for the bending test considering the flow-dependent tensile behavior of the UHSFRC. From the simulation for the fiber orientation distribution according to the flow distance, it could be found that the major change in the fiber orientation distribution took place within a short flow distance and most of the fibers became nearly aligned to the flow direction. After some flow distance, there was a not-so-remarkable variation in the fiber orientation distribution that could influence the tensile behavior of the composite. For this flow region, the consistent flexural test results, regardless of flow distance, demonstrate the reliability of the simulation.


Cooperation and competition between dentists and denturists in Finland.
The aim of this study was to investigate cooperation between dentists and denturists in Finland, particularly in relation to perceived competition between the two professions. From a representative sample of 350 private dentists and 253 denturists, 68% returned acceptably filled-in questionnaires dealing with competition and cooperation with other healthcare professionals. Dentists referred their patients significantly (P < 0.001) less often to denturists (26.2%) than denturists did to dentists (94.1%). Those who referred their patients to members of the other profession also received patients from the other profession significantly (P< 0.001) more often than those who did not (60.7% vs 16.7% among dentists; 90.0% vs 44.4% among denturists). Denturists saw themselves as competing with dentists (56.0%) significantly (P< 0.001) more often than dentists did with denturists (29.2%). Dentists practicing in small towns or rural areas cooperated more often with denturists than did those practicing in more urban areas. Among denturists, the likelihood of referring patients to dentists was associated with younger age and fewer clinical working hours. It was concluded that cooperation between dentists and denturists was common. Oral healthcare professionals who referred their patients to the other profession also benefited by receiving more patients on referral from them. Dental services provided by denturists are limited, which may explain their greater willingness to cooperate with dentists.


Mandibular reconstruction with TMJ prosthesis: management of osteomyelitis after orthognathic surgery (Case Report).
This case report presents a mandible reconstruction with temporomandibular joint (TMJ) prothesis for treatment of osteomyelitis infection following a bimaxillary orthognathic and genioplasty surgeries. The patient, a 41-year-old female, presented with facial pain, difficulty in opening her mouth, and mandibular deviation four months after the initial orthognathic surgery. During the four months, the patient had experienced two more surgerys post-operative for treatment of the complications. Examination revealed mobility between osteotomy segments of the right mandibular osteotomomie between body and ramus, and Computer Tomographic scan analysis revealed osteomyelitis and non-union within the osteotomy side of the right mandible from the previous surgery. Due to the advanced state of the disease and significant bone resorption, treatment was planned in two stages, involving bone debridement and then reconstruction with a custom made extended temporomandibular joint prosthesis. The patient had no postoperative complications and achieved satisfactory functional and aesthetic outcomes. This case emphasizes the importance of careful monitoring and prompt management of postoperative complications following orthognathic surgery to prevent rare but serious complications such as osteomyelitis.


Interventions for wound healing among diabetic patients infected with Staphylococcus aureus: a systematic review.
Staphylococcus aureus is the most frequent agent isolated in diabetic foot infections and may be associated with changes to wound healing times. The aim of this study was to perform a systematic review of the literature, including studies that assessed the efficacy of any clinical or surgical intervention, as well as oral or topical therapy for diabetic ulcers infected with S. aureus. Systematic review with a search conducted in databases. We conducted a systematic review with a comprehensive search in the Lilacs, SciELO, PubMed/Medline, Old Medline, Embase and Cochrane Library databases, for articles published from 1966 to 2010. The articles selected were limited to studies on diabetic patients with wounds infected with S. aureus for whom their healing was followed up, with the use of either antibiotics or experimental treatments. Animal studies and those that did not report the wound healing, as well as review articles, were excluded. Five studies that met the inclusion and exclusion criteria were analyzed. There are few studies reporting the healing of wounds infected with S. aureus in diabetic patients, although this is the most commonly found pathogen in this type of wound and it frequently consists of methicillin-resistant S. aureus (MRSA). There is insufficient evidence to support early use of broad-spectrum antibiotics against MRSA to promote healing of diabetic ulcers, since antibiotic resistance may develop from such treatment. This highlights the need for further studies on the subject.


Albiflorin ameliorates obesity by inducing thermogenic genes via AMPK and PI3K/AKT in vivo and in vitro.
Brown adipose tissue (BAT) activation has been identified as a possible target to treat obesity and to protect against metabolic diseases by increasing energy consumption. We explored whether albiflorin (AF), a natural compound, could contribute to lowering the high risk of obesity with BAT and primary brown preadipocytes in vivo and in vitro. Human adipose tissue-derived mesenchymal stem cells (hAMSCs) were cultured with adipogenic differentiation media with or without AF. Male C57BL/6J mice (n=5 per group) were fed a high-fat diet (HFD) for six weeks with or without AF. Brown preadipocytes from the interscapular BAT of mice were cultured with or without AF. In white adipogenic differentiation of hAMSCs, AF treatment significantly reduced the formation of lipid droplets and the expression of adipogenesis-related genes. In HFD-induced obese C57BL/6J mice, AF treatment significantly reduced body weight gain as well as the weights of the white adipose tissue, liver and spleen. Furthermore, AF induced the expression of genes involved in thermogenic function in BAT. In primary brown adipocytes, AF effectively stimulated the expressions of thermogenic genes and markedly up-regulated the AMP-activated protein kinase (AMPK) signaling pathway. Pretreatment with phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 nullified the induction of the thermogenic genes by AF in primary brown adipocytes. Moreover, AF activated beige cell marker genes induced by the pharmacological activation of peroxisome proliferator-activated receptor γ in hAMSCs. This study shows that AF prevents the development of obesity in hAMSCs and mice fed an HFD and that it is also capable of stimulating the differentiation of brown adipocytes through the modulation of thermogenic genes by AMPK and PI3K/AKT.


Are religiosity and spirituality useful constructs in drug treatment research?
Religiosity and spirituality (R/S) have been shown to be related to better outcomes in many health service areas, including drug abuse treatment. The latter area, however, lacks a fully emergent empirical framework to guide further study. Moreover, although scientists have tested isolated hypotheses, no comprehensive process model has been designed and validated, limiting conceptual development as well. This paper reviews the relevant R/S and health research literature with a primary focus on drug treatment processes. Then a conceptual model is suggested to guide future incremental study of R/S assessment and intervention development. Implications for addiction health services include increased efforts to empirically validate R/S interventions, to increase practitioner competencies in this area, and to disseminate relevant research findings.


If you build (and moderate) it, they will come: the Smokefree Women Facebook page.
This analysis explores the impact of modifying the Smokefree Women Facebook social media strategy, from primarily promoting resources to encouraging participation in communications about smoking cessation by posting user-generated content. Analyses were performed using data from the Smokefree Women Facebook page to assess the impact of the revised strategy on reach and engagement. Fan engagement increased 430%, and a strong and statistically significant correlation (P < .05) between the frequency of moderator posts and community engagement was observed. The reach of the page also increased by 420%. Our findings indicate that the strategy shift had a statistically significant and positive effect on the frequency of interactions on the Facebook page, providing an example of an approach that may prove useful for reaching and engaging users in online communities. Additional research is needed to assess the association between engagement in virtual communities and health behavior outcomes.


Not in one metric: Neuroticism modulates different resting state metrics within distinctive brain regions.
Neuroticism is a complex personality trait encompassing diverse aspects. Notably, high levels of neuroticism are related to the onset of psychiatric conditions, including anxiety and mood disorders. Personality traits are stable individual features; therefore, they can be expected to be associated with stable neurobiological features, including the Brain Resting State (RS) activity as measured by fMRI. Several metrics have been used to describe RS properties, yielding rather inconsistent results. This inconsistency could be due to the fact that different metrics portray different RS signal properties and that these properties may be differently affected by neuroticism. To explore the distinct effects of neuroticism, we assessed several distinct metrics portraying different RS properties within the same population. Neuroticism was measured in 31 healthy subjects using the Zuckerman-Kuhlman Personality Questionnaire; RS was acquired by high-resolution fMRI. Using linear regression, we examined the modulatory effects of neuroticism on RS activity, as quantified by the Amplitude of low frequency fluctuations (ALFF, fALFF), regional homogeneity (REHO), Hurst Exponent (H), global connectivity (GC) and amygdalae functional connectivity. Neuroticism modulated the different metrics across a wide network of brain regions, including emotional regulatory, default mode and visual networks. Except for some similarities in key brain regions for emotional expression and regulation, neuroticism affected different metrics in different ways. Metrics more related to the measurement of regional intrinsic brain activity (fALFF, ALFF and REHO), or that provide a parsimonious index of integrated and segregated brain activity (HE), were more broadly modulated in regions related to emotions and their regulation. Metrics related to connectivity were modulated across a wider network of areas. Overall, these results show that neuroticism affects distinct aspects of brain resting state activity. More in general, these findings indicate that a multiparametric approach may be required to obtain a more detailed characterization of the neural underpinnings of a given psychological trait.


Combined lung and liver procurement in controlled donation after circulatory death using normothermic abdominal perfusion. Initial experience in two Spanish centers.
Combining simultaneously lung and liver procurement in controlled donation after circulatory death (cDCD) using normothermic abdominal perfusion (NRP) for abdominal grafts and cooling and rapid recovery technique (RR) for the lungs increases the complexity of the procurement procedure and might injure the grafts. A total of 19 cDCDs from two centers using this combined procedure were evaluated, and 16 liver and 21 lung transplantations were performed. As controls, 34 donors after brain death (DBDs) were included (29 liver and 41 lung transplantations were performed). Two cDCD liver recipients developed primary nonfunction (12.5%). No cases of ischemic cholangiopathy were observed among cDCD recipients. The 1-year and 2-year liver recipients survival was 87.5% and 87.5% for the cDCD group, and 96% and 84.5% for the DBD group, respectively (P = .496). The 1-year and 2-year lung recipients survival was 84% and 84% for the cDCD group and 90% and 90% for the DBD group, respectively (P = .577). This is the largest experience ever reported in cDCD with the use of NRP combined with RR of the lungs. This combined method offers an outstanding recovery rate and liver and lung recipients survival comparable with those transplanted with DBDs. Further studies are needed to confirm our findings.


Engineering Aromatic-Aromatic Interactions To Nucleate Folding in Intrinsically Disordered Regions of Proteins.
Aromatic interactions are an important force in protein folding as they combine the stability of a hydrophobic interaction with the selectivity of a hydrogen bond. Much of our understanding of aromatic interactions comes from "bioinformatics" based analyses of protein structures and from the contribution of these interactions to stabilizing secondary structure motifs in model peptides. In this study, the structural consequences of aromatic interactions on protein folding have been explored in engineered mutants of the molten globule protein apo-cytochrome b5. Structural changes from disorder to order due to aromatic interactions in two variants of the protein, viz., WF-cytb5 and FF-cytb5, result in significant long-range secondary and tertiary structure. The results show that 54 and 52% of the residues in WF-cytb5 and FF-cytb5, respectively, occupy ordered regions versus 26% in apo-cytochrome b5. The interactions between the aromatic groups are offset-stacked and edge-to-face for the Trp-Phe and Phe-Phe mutants, respectively. Urea denaturation studies indicate that both mutants have a Cm higher than that of apo-cytochrome b5 and are more stable to chaotropic agents than apo-cytochrome b5. The introduction of these aromatic residues also results in "trimer" interactions with existing aromatic groups, reaffirming the selectivity of the aromatic interactions. These studies provide insights into the aromatic interactions that drive disorder-to-order transitions in intrinsically disordered regions of proteins and will aid in de novo protein design beyond small peptide scaffolds.


High-Capacity Drug Carriers from Common Polymer Amphiphiles.
We report herein a dual-purpose role for polyacidic domains in an aqueous-phase polymer amphiphile assembly. In addition to their typical role as ionized water-solubilizing and self-repulsive motifs, we find that polycarboxylic acid domains uniquely enable high levels of hydrophobic drug encapsulation. By attenuated total reflectance infrared spectroscopy, we find significant differences in the carbonyl stretching region of the nanoparticles formed by polyacidic amphiphiles relative to those in soluble, single-domain poly(acrylic acid), suggesting that stabilization may be derived from limited ionization of the carboxylate groups upon assembly. Acidic-hydrophobic diblock polyacrylates were prepared and coassembled with up to 60 wt % camptothecin (CPT) into nanoparticles, the highest loading reported to date. Controlled release of bioactive CPT from polymer nanoparticles is observed, as well as protection from human serum albumin-induced hydrolysis. Surface protection with PEG limits uptake of the CPT-loaded nanoparticles by MCF-7 breast cancer cells, as expected. Acidic-hydrophobic polymer amphiphiles thus have the hallmarks of a useful and general drug delivery platform and are readily accessible from living radical polymerization of cheap, commercially available monomers. We highlight here the potential utility of this common polymer design in high-capacity, controlled-release polymer nanoparticle systems.


Intravenous Thrombolysis Guided by Perfusion CT with Alteplase in >4.5 Hours from Stroke Onset.
The benefit of intravenous thrombolysis (IVT) in wake-up stroke (WUS), stroke of unknown time of onset (SUKO), or when time exceeds 4.5 h from last-seen-normal (LSN) guided by CT perfusion (CTP) or MRI has been recently suggested. However, there is limited information of IVT in those patients in real-world studies. Our aim was to evaluate safety and efficacy of IVT selected by CTP in patients with WUS, SUKO, or stroke of time onset beyond 4.5 h. We studied a prospective cohort of patients who underwent IVT from January 2010 to December 2017. Two groups were defined: standard of care group (SC) included patients with time onset <4.5 h and CTP group included patients with WUS, SUKO, or onset beyond >4.5 h from LSN with penumbra area in CTP. We evaluated baseline characteristics, functional outcomes according to modified Rankin Scale (mRS) at discharge and at 90 days, and intracranial hemorrhages rates. 657 patients were studied: 604 (92%) were treated in the SC group and 53 (8%) in the CTP group. The mean NIHSS score was 9.8 in the CTP group versus 13 in the SC group (p = 0.001). Seventeen patients in the CTP group (32.1%) received bridging therapy with mechanical thrombectomy (MT). Last time seen well-to-needle time was 538 versus 155 min (p < 0.001). The incidence of symptomatic intracranial hemorrhage was equal in both groups (3.8 vs. 3.8%, p = 1). Good functional outcome (mRS < 2) was achieved in both groups (72 vs. 60.4%, p = 0.107). IVT in patients with WUS, SUKO, or stroke beyond >4.5 h from LSN, with salvageable brain tissue on CTP, seems to be safe and has similar functional outcomes at 90 days to the standard therapeutic window, even when combined with MT.


Is tendinitis an inflammatory disease initiated and driven by pro-inflammatory cytokines such as interleukin 1β?
Tendonitis and tendinitis are terms used to describe an inflamed and painful tendon. Tendinopathy, is a descriptive term for describing clinical conditions arising from tendon injury and overuse both within and around tendons. The aim of this mini-review is to explore the role of pro-inflammatory cytokines, particularly interleukin-1β (IL-1β) in tendon disorders. A number of investigators including our group have proposed that pro-inflammatory cytokines such as IL-1β are initiators of tendinopathies, stimulating inflammation, apoptosis and extracellular matrix (ECM) degradation. This is one of the reasons why IL-1β is frequently used in culture models of tendon inflammation to study the inflammatory and catabolic responses of tenocytes. However, some researchers oppose this view and suggest that although IL-1β may play a role in rheumatoid arthritis (RA) and osteoarthritis (OA), the involvement of IL-1β in the development of tendinopathy is questionable. This mini-review discusses the relevant papers published in this area and summarises the evidence for and against the involvement of pro-inflammatory cytokines such as IL-1β in tendonitis. Reaching a consensus will be important for the development and refinement of biomimetic models of tendon inflammation and the formulation of new therapeutic strategies for the treatment of tendon injuries.


Measurement of the intensity-dependent atomic dipole phase of a high harmonic by frequency-resolved optical gating.
The temporal profile and phase of the fifth harmonic of a Ti:sapphire laser were fully characterized by two-photon ionization frequency-resolved optical gating technique for the first time. The fifth harmonic was found to have negative chirp and the pulse compression was demonstrated. The negative chirp is well explained by using a zero-range potential model. This technique is scalable to extreme ultraviolet (XUV) and soft x-ray regions by using currently available light sources, making it possible to measure the pulse duration and phase of vacuum ultraviolet, XUV, and soft x-ray pulses.


Non-monotonic temperature dependence of radiation defect dynamics in silicon carbide.
Understanding response of solids to particle irradiation remains a major materials physics challenge. This applies even to SiC, which is a prototypical nuclear ceramic and wide-band-gap semiconductor material. The lack of predictability is largely related to the complex, dynamic nature of radiation defect formation. Here, we use a novel pulsed-ion-beam method to study dynamic annealing in 4H-SiC ion-bombarded in the temperature range of 25-250 °C. We find that, while the defect recombination efficiency shows an expected monotonic increase with increasing temperature, the defect lifetime exhibits a non-monotonic temperature dependence with a maximum at ~100 °C. This finding indicates a change in the dominant defect interaction mechanism at ~100 °C. The understanding of radiation defect dynamics may suggest new paths to designing radiation-resistant materials.


The Double-Transforaminal Lumbar Interbody Fusion: An Innovative One-Stage Surgical Technique for Posterior Kyphosis Correction.
Posttraumatic deformities after vertebral fractures are challenging for orthopedic surgeons in the non-operative and operative field. Especially osteoporotic fractures may cause a hyperkyphosis resulting in segmental or global sagittal imbalance and chronic back pain. Different vertebral osteotomies are potent to restore sagittal profile but show a very high perioperative risk including neurological and soft tissue complications. In addition, some of these extensive operations require a two-step procedure including posterior and anterior approaches. Therefore, these established techniques may be contraindicated in elderly or multimorbide patients suffering from concomitant diseases. The authors describe the double transforaminal lumbar interbody fusion (TLIF) osteotomy (DTO) as an innovative one-stage and low-invasive surgical technique to correct a fixed posttraumatic kyphosis in the thoracolumbar junction. The procedure includes posterior release (laminectomy, facettectomy, nucleotomy) combined with two expandable TLIF implants (sandwich technique) and posterior instrumentation and is illustrated by a case of a multimorbide 78-year old female.


Global profiling of protein lactylation in Caenorhabditis elegans.
Lactylation, as a novel posttranslational modification, is essential for studying the functions and regulation of proteins in physiological and pathological processes, as well as for gaining in-depth knowledge on the occurrence and development of many diseases, including tumors. However, few studies have examined the protein lactylation of one whole organism. Thus, we studied the lactylation of global proteins in Caenorhabditis elegans to obtain an in vivo lactylome. Using an MS-based platform, we identified 1836 Class I (localization probabilities > 0.75) lactylated sites in 487 proteins. Bioinformatics analysis showed that lactylated proteins were mainly located in the cytoplasm and involved in the tricarboxylic acid cycle (TCA cycle) and other metabolic pathways. Then, we evaluated the conservation of lactylation in different organisms. In total, 41 C. elegans proteins were lactylated and homologous to lactylated proteins in humans and rats. Moreover, lactylation on H4K80 was conserved in three species. An additional 238 lactylated proteins were identified in C. elegans for the first time. This study establishes the first lactylome database in C. elegans and provides a basis for studying the role of lactylation.


Generation of apoptosis-resistant HEK293 cells with CRISPR/Cas mediated quadruple gene knockout for improved protein and virus production.
Apoptosis has important functions during pathophysiologic processes. However, from a biopharmaceutical point of view, active apoptosis of host cells is undesirable during viral packaging or protein expression, because it decreases the efficiency of viral or protein production. Here we used the CRISPR/Cas technique to knock out four pro-apoptotic genes, Caspase3, Caspase6, Caspase7 and AIF1, in HEK293 cells, and successfully produced an apoptosis-resistant cell line. Furthermore, this cell line showed higher expression levels of pro-apoptotic proteins and higher packaging efficiency for the virus carrying these proteins than control HEK293 cells. This study not only produced an apoptosis-resistant cell line that is useful in producing apoptosis-inducing proteins or viruses expressing these proteins, but also provides a methodology to build other apoptosis-resistant cell lines.


"Anemone" cell (villiform) tumor of the brain.
At age 31, the patient developed hydrocephalus secondary to a brain lesion that had been present for 12 years. A ventriculoperitoneal shunt was performed, but a stereotactic biopsy did not establish a definitive diagnosis at that time. At age 34 the patient experienced spontaneous intratumoral and ventricular hemorrhage, which prompted radical surgical resection of the lesion. Histologic and immunocytochemical findings established a diagnosis of ependymoma; review of the ultrastructure of the tumor from the biopsy performed when the patient was 31 years old revealed the characteristics of an "anemone" cell neoplasm.


Single-Crystalline α-Al2 O3 Nanotubes Converted from Al4 O4 C Nanowires.
Single-crystalline Al4 O4 C nanowires can be synthesized at a high yield via a simple high-temperature solid reaction. A two-step method has been developed to convert the prepared nanowires into single-crystalline α-Al2 O3 nanotubes. These nanotubes may find high-temperature applications due to their unmatched refractory properties.


A rare case of Paget's disease of the bone in the Philippines.
A 40-year-old Filipina presented with a 2-year history of progressive bilateral inguinal and hip pain with limited range of motion. She had a bad fall which led to widespread body pains for 6 months partially relieved on multiple analgesic and anti-inflammatory agents. There was progressive weight loss and anemia. Focused musculoskeletal examination revealed moderate degree of generalized muscle atrophy, pain-limited range of motion of bilateral hip and shoulder joints, with equivocal muscle strength of both proximal and distal muscle groups of all extremities. Metastatic bone disease was ruled out when skeletal survey disclosed mixture of osteolytic and osteoblastic lesions, predominantly osteoblastic, on multiple sites. Bone turnover markers were elevated. Bone biopsy revealed histopathologic results compatible with Paget's disease of the bone. Management included oral calcium and vitamin D supplement followed by parenteral zoledronic acid, and a rehabilitation program. Four months after bisphosphonate therapy, the patient reported significant relief of symptoms with complete resolution of the previously noted generalized body pains, although she ambulates with use of an assistive device. Due to the rarity of the condition among Filipinos, this case was a diagnostic dilemma in itself, as it is most likely the first published case in the Philippine literature.


Anatomical variations and dimensions of arteries in the anterior part of the circle of Willis.
The aim of this study was to investigate different anatomic variations and dimensions of anterior part of the circle of Willis (CW) and their prevalence on Kosovo's population. This is an observational descriptive and retrospective study performed at the University Clinical Centre, Clinic of Radiology. The three-dimensional time-of-flight technique was used for magnetic resonance angio- graphy imaging to evaluate the anatomy of the CW in 513 adults without clinical manifestations for cerebrovascular disease. The diameters of arteries of the CW were measured and variations were recorded. The complete anterior part of CW was found in 64.3% of cases, more evident in female at about 66% than male 62.2%. Morphologic variations of the ACA1 are agenesis or hypoplasia in 5.65%, fusion of the anterior cerebral arteries (ACAs) on a short distance in 6.5% and fusion of the ACA on a long distance in 2.5%, median ACA is presented in 11 examined patients or 2.1%. Normal anterior communicating artery (ACoA) was seen in 68.2%, hypoplasia or absence 15.66%, double ACoA in 0.6% and fenestrations in 3.89%. The mean calibrations of the vessels were measured as 2.04 mm in right A1, 2.06 mm in left A1 and 1.16 mm of ACoA. While, 14.1 mm length of right A1, 13.87 mm of left A1 and 2.99 mm of ACoA. Knowledge of the variations and diameter of the anterior part of the CW has a great importance in determination of anatomical variations and diameter in general populations, also, in interventional radiology for various endovascular interventions as well as during anatomy lessons.


Corrosion casts of convoluted testicular arteries in mice and rats.
The preparation of vascular corrosion casts enables us to observe the minute features of blood vessels. For mice and rats, reports on the macroscopical appearance of testicular arteries with the cast technique have been quite limited. Therefore, in the present study, we tried to prepare corrosion casts of such arteries in order to observe the three-dimensional structures in mice and rats. Vascular casts of testicular arteries were produced by intravenous injection of a polymethylmethacrylate solution, followed by treatment of the whole animal bodies with NaOH. Additionally, the gross appearance of human testicular arteries in cadavers was compared with that of the vascular casts. The results showed that the testicular arteries of humans, mice, and rats run from the abdominal aorta to the testes, with various configurations (straight, meandering, spiral, or coiled forms), and each species exhibits a specific pattern. The specific forms of testicular arteries may play several roles in protection of normal spermatogenesis, such as allowing wide mobility of the testes on physical attack, heat emission with the entwined pampiniform plexus, and reduction of the blood flow rate. The great extension of the testicular arteries during the fetal period from the upper abdomen to the scrotum when the testes descend might be another feature of the specific development of their running configuration.


Clinical study of bladder cancer: Proteinuria as a predictor of recurrence and efficacy of intravesical bacille Calmette-Guerin therapy.
We studied the clinical characteristics of bladder cancer, with special attention to the clinical and pathological variables that affect tumor stage, relapse and efficacy of intravesical therapy. We reviewed the medical records of 152 patients of the Saiseikai Central Hospital who had been diagnosed as having bladder cancer between 1981 and 2001. The age of the patients ranged from 24 to 88 years, with a median of 63.5 years. The median follow up was 52.4 months (range, 0.5-259.5 months). There was no difference in the incidence of gross hematuria as a presenting symptom among the patients with invasive cancer, superficial cancer and carcinoma in situ (CIS). However, the incidence of urinary frequency and painful urination did differ significantly between patients. Although patients with invasive cancer had a longer time to hospital visit than those with superficial cancer, this time difference was not statistically significant. Presence of proteinuria, multifocality and intravesical bacille Calmette-Guerin (BCG) therapy were the significant predictors of relapse after transurethral resection (TUR). Presence of proteinuria was shown to adversely affect the efficacy of intravesical BCG therapy. In the BCG-treated group, 3-year relapse-free survival was 78.4% for patients without proteinuria and 40.0% for those with proteinuria; this difference was statistically significant (P = 0.0277). Time to hospital visit did not influence the pathological stage of cancer in patients included in the present study. Presence of proteinuria, multifocality and BCG therapy were the significant predictors of relapse after TUR. Presence of proteinuria was shown to adversely affect the efficacy of intravesical BCG therapy. Proteinuria might be helpful in predicting tumor relapse and efficacy of intravesical BCG therapy in clinical settings, along with other markers.


High-pressure assisted extraction of bioactive compounds from industrial fermented fig by-product.
High-pressure assisted extraction was employed to obtain fig by-product derived extracts and its impact was evaluated on antioxidant activity and total phenolic, tannin, and flavonoid. A Box-Behnken design was applied to evaluate the effects of pressure, extraction time and ethanol concentration on extractions and optimal conditions were estimated by response surface methodology. The correlation analysis of the mathematical-regression model indicated that a quadratic polynomial model could be employed to optimize the high pressure extraction of compounds. Only the models developed for total antioxidant activity by DPPH · and for total flavonoids presented coefficient determinations lower than 0.95. From response surface plots, pressure, extraction time and ethanol concentration showed independent and interactive effects. The optimal conditions included 600 MPa, an extraction time between 18 and 29 min, depending on the parameter analyzed and a low ethanol concentration (<15%) except for flavonoids (48%). High pressure led to an increase of 8-13% of antioxidant activity and an increase of 8-11% of total phenolics, flavonoids and tannins content when compared to extracts performed at 0.1 MPa. Analysis of variance indicated a high goodness of fit of the models used and the adequacy of response surface methodology for optimizing high pressure extraction.


Solution of the linearized Poisson-Boltzmann equation.
Improved methods are formulated for solution of the linearized Poisson-Boltzmann equation, to be used in conjunction with electronic structure calculation on a solute together with dielectric continuum representation of the salt-containing solvent. Volume polarization effects due to quantum mechanical penetration of solute charge density outside the cavity that excludes solvent are treated by exact and by approximate methods analogous to those previously developed for the salt-free case. With boundary element approaches, exact solutions lead to coupled equations for a pair of cavity surface distributions that mimic the polarization of the solvent dielectric and the ionic atmosphere. A novel means is found to effectively decouple these equations, yielding more efficient practical methods for their numerical solution. Detailed comparisons are given to related boundary element formulations previously reported in the literature, which neglect volume polarization, and analogous decoupling is also found for the pair of surface distributions invoked there. Illustrative results are provided for a simple spherical example.


Expression profiling of a high-fertility mouse line by microarray analysis and qPCR.
In a recent study it was demonstrated that a largely increased ovulation number is responsible for high prolificacy in two mouse lines selected for fertility performance. The objective of the present study was to identify genes that are involved in increasing the ovulation number in one of these lines, FL1. For differential expression profiling, ovaries of FL1 and of a non-selected control line, DUKsi, both lines derived from the same genetic pool, were analyzed with microarray analysis and quantitative polymerase chain reaction (qPCR). Ovaries from 30 animals of each line were collected at the metestrous stage, combined to 6 pools each, and processed for microarray analysis. The actual number of ova shed in FL1 exceeded that of the DUKsi control line more than twofold (26.6 vs. 12.9). 148 differentially expressed ovarian transcripts could be identified, 74 of them up- and 74 down-regulated. Of these, 47 significantly mapped to specific Gene Ontology (GO) terms representing different biological processes as steroid metabolism, folliculogenesis, immune response, intracellular signal transduction (particularly of the G protein signaling cascade), regulation of transcription and translation, cell cycle and others. qPCR was used to re-evaluate selected transcripts and to estimate inter-individual variation of expression levels. These data significantly correlated with microarray data in 12 out of 15 selected transcripts but revealed partly large variations of expression levels between individuals. (1) The abundance of numerous ovarian transcripts was significantly different in FL1 compared to the non-selected control line DUKsi thus suggesting that at least some of the respective genes and corresponding biological processes are involved in improving reproductive traits, particularly by increasing the number of ovulation. (2) Selective qPCR re-evaluation largely confirmed the microarray data and in addition demonstrated that sample pooling can be beneficial to find out group-specific expression profiles despite of large inter-individual variation. (3) The present data will substantially help ongoing genetic association studies to identify candidate genes and causative mutations responsible for increased fertility performance in mice.


A coarse-grain model for entangled polyethylene melts and polyethylene crystallization.
The Shinoda-DeVane-Klein (SDK) model is herein demonstrated to be a viable coarse-grain model for performing molecular simulations of polyethylene (PE), affording new opportunities to advance molecular-level, scientific understanding of PE materials and processes. Both structural and dynamical properties of entangled PE melts are captured by the SDK model, which also recovers important aspects of PE crystallization phenomenology. Importantly, the SDK model can be used to represent a variety of materials beyond PE and has a simple functional form, making it unique among coarse-grain PE models. This study expands the suite of tools for studying PE in silico and paves the way for future work probing PE and PE-based composites at the molecular level.


G-Tetraplex-Induced FRET within Telomeric Repeat Sequences Using (Py) A-(Per) A as Energy Donor-Acceptor Pair.
G-tetraplex induced fluorescence resonance energy transfer (FRET) within telomeric repeat sequences has been studied using a nucleoside-tethered FRET pair embedded in the human telomeric G-quadruplex forming sequence (5'-A GGG TT(Py) A GGG TT(Per) A GGG TTA GGG-3', Py=pyrene, Per=perylene). Conformational change from a single strand to an anti-parallel G-quadruplex leads to FRET from energy donor ((Py) A) to acceptor ((Per) A). The distance between the FRET donor/acceptor partners was controlled by changing the number of G-quartet spacer units. The FRET efficiency decreases with increase in G-quartet units. Overall findings indicate that this could be further used for the development of FRET-based sensing and measurement techniques.


The evolution of medulloblastoma therapy to personalized medicine.
Recent advances in cancer genomics have revolutionized the characterization and classification of medulloblastomas. According to the current WHO guidelines, medulloblastomas are now classified into the following molecularly defined groups: Wnt signaling pathway (WNT)-activated, sonic hedgehog signaling pathway (SHH)-activated and tumor suppressor protein p53 (TP53)-mutant, SHH-activated and TP53-wildtype, and non-WNT/non-SHH (i.e. group 3 and group 4). Importantly, genomic, epigenomic, and proteomic advances have created a potential paradigm shift in therapeutic options. The challenge now is to (i) translate these observations into new therapeutic approaches and (ii) employ these observations in clinical practice, utilizing the classification following a molecular analysis for diagnosis and application of new subgroup-specific targeted therapeutics.


Leaky pipeline, gender bias, self-selection or all three? A quantitative analysis of gender balance at an international palliative care research conference.
The 'leaky pipeline' in academia is a clearly described phenomenon, but has not been examined in palliative care. We analysed the gender balance of speakers at the 9th World Research Congress of the European Association of Palliative Care (EAPC) to test the null hypothesis that there is no difference in the proportion of women and men with senior academic visibility in palliative care conference programmes. The final programme of the 2016 EAPC World Congress was examined, and the gender of each speaker was recorded. Presentations were assessed using a three-tier hierarchy of senior academic visibility: Free Communication sessions, Themed sessions and invited Plenaries (low to high). As there was only one Invited Plenary at EAPC 2016, we examined the gender balance at EAPC Plenaries from 2012 to 2016. Overall, the majority of speakers at EAPC 2016 (96/130, 73.8%) were women. The proportion of women was highest in the Free Communication sessions (84/107, 78.5%). In the Themed sessions, women made up just over half of speakers (12/22, 54.5%). In 2016, there was 1 invited Plenary speaker, a man. From 2012 to 2016, just 6 of 23 invited Plenary speakers at EAPC conferences have been women (26.1%) (χ2=25.4, p<0.001). These data reject our null hypothesis and suggest that there is attrition of women along the academic pipeline in palliative care. Other factors such as self-selection (that women decline invitations to give talks) and unconscious gender bias need further exploration, as well as actions to address the imbalance.


Human albumin binding of tamoxifen in the presence of a perfluorochemical erythrocyte substitute.
The binding of tamoxifen (an HSA site IV ligand) to human serum albumin (HSA) in the presence of a perfluorochemical (PFC) erythrocyte substitute has been examined. Standard centrifugation followed by supernatant ultrafiltration was used to study the binding of 0.1 and 0.5 microgram mL-1 tamoxifen at ambient conditions. Tamoxifen was extensively bound (greater than 99%) to the PFC emulsion through an association with the emulsifiers of the droplets. Tamoxifen was also extensively bound (greater than 99%) to HSA. The percent free tamoxifen increased upon HSA dilution. Tamoxifen was extensively bound by various mixtures of HSA and the PFC emulsion and the percent free drug was similar to those obtained with HSA alone. However, the position of drug binding (PFC emulsion vs HSA) varied significantly with changes in the ratio of PFC emulsion to HSA. This could be important in terms of the different distribution of HSA and PFC emulsion in the body. Studies with PFC emulsion components indicated that any displacement of HSA-bound tamoxifen by the PFC emulsion was due to the oleic acid and, to a much smaller degree, Pluronic F-68 components. Other HSA site IV ligands are expected to be similarly displaced.


Ages and Stages Questionnaires-3 developmental screening of infants and young children with cancer.
The Ages and Stages Questionnaires-3® (ASQ-3) for developmental screening in our young oncology patients was pilot tested in children 4 to 48 months of age with newly diagnosed cancer. Subjects were screened within 28 days of diagnosis (baseline), at 6 and 12 months. Twenty-six of 30 enrolled parents (87%) completed all 3 screens. Screens were completed by parents within 15 minutes. ASQ-3 screening identified unsuspected developmental delays as follows: 7 at baseline, 4 at 6 months, and 3 at 12 months. ASQ-3 developmental screening is feasible, identifies early developmental delays in young children with cancer, and helps initiate appropriate referrals.


Improved in situ hybridization to HIV with RNA probes derived from PCR products.
These experiments tested the hypothesis that a pool of PCR-derived RNA probes with defined length and even representation of the target sequences could produce more specific and intense in situ hybridization signals than randomly size-reduced, plasmid-derived RNA probes. In situ hybridization was performed with sense and anti-sense HIV-1 RNA probes that were derived from PCR products tailed with the T7 RNA polymerase promoter or from plasmid DNA. In situ hybridization using a pool of seven anti-sense or sense PCR-derived RNA probes (1805 nucleotides of HIV sequence, 257 nucleotides average probe length) was compared with hybridization using anti-sense or sense RNA probes made from a plasmid representing the HIV-1 env gene (3151 nucleotides of HIV-1 target). The pooled PCR-derived probes resulted in stronger in situ hybridization signals and less background than those produced with plasmid-derived RNA probes. This method for creating PCR-derived RNA probes improves the feasibility of synthesizing multiple, discrete RNA probes for studies of specific mRNA expression because it does not require the subcloning steps used to construct plasmids. PCR-derived RNA probes may provide a viable alternative to the use of plasmid-derived RNA probes for in situ hybridization.


Vascular density profile of rat mammary carcinomas induced by 1-methyl-1-nitrosourea: implications for the investigation of angiogenesis.
Given the mounting interest in studying the effects of various cancer preventive regimes on the angiogenic process in autochthonously growing mammary tumors, the experiment reported here was conducted to identify factors that should be considered in the collection of data from experiments in which a primary endpoint is the measurement of blood vessel density as a reflection of angiogenic activity. Female Sprague-Dawley rats were injected i.p. with 50 mg 1-methyl-1-nitrosourea (MNU)/kg body weight at 21 days of age. Tumor-bearing rats were killed 35 days post-carcinogen. Immunohistochemical detection of blood vessels using antiserum directed against the CD31 epitope was performed on paraffin sections of 36 carcinomas representing four histological types. Census counting was used to detect all blood vessels that were subsequently divided into one of five vessel size categories. Vessels were counted in both the intra-tumoral region and in a 50 microm width band of mammary tissue circumscribing each tumor; the circumscribed area was referred to as the extra-tumoral region. Vascular density was reported in units of vessel counts or vessel area per unit of assessed area. Overall, vascular density was observed to be highly variable and was not affected by tumor histology. Vascular density in the extra-tumoral region was significantly higher than in the intra-tumoral region. Correlation analyses indicated that similar information was obtained when vascular density was reported as either vessel counts or vessel area; however, correlations across vessel size categories and between the intra-tumoral and extra-tumoral regions were low and generally not statistically significant. Collectively, the data provide a complete description of vascularization in autochthonously growing mammary tumors, and a reference for comparison in studies of various cancer preventive agents that modulate the angiogenic process.