[Present-day hygienic aspects of dealing with industrial and consumption waste].
The article covers scientific hygienic positions in forming and solving the acute scientific and technical problem of dealing with waste. The given problem is topical due to growing amount and diversity of waste and relatively small knowledge of ecological, medical and biological aspects of the problem. The paper covers the entire "life cycle" of waste, chiefly industrial and communal, as the most diverse and potentially dangerous to the environment. Special attention is paid to neutralization and recycling of waste for its application as secondary material in various branches of national economy. Having critically analized the results of complex studies, the authors conclude the article with outlining the prospective tasks of research for scientific and practical institutions of sanitary surveillance of Russian Federation Ministry of Health.


Relationship between receptors mediating serotonin (5-HT) contractions in the canine basilar artery to 5-HT1, 5-HT2 and rat stomach fundus 5-HT receptors.
The receptors responsible for contraction to serotonin (5-HT) in the canine basilar artery have not been definitively established to date. Several selective 5-HT2 receptor antagonists (spiperone, ketanserin and LY53857) did not inhibit markedly 5-HT-induced contractions in the canine basilar artery in doses higher than required for substantial inhibition of 5-HT2 receptor-mediated responses. These data suggest that the receptors mediating 5-HT-induced contractions in the basilar artery are not 5-HT2 receptors. Using a series of 5-HT antagonists with relatively high affinity at 5-HT1 sites, over a 1000-fold difference occurred in their ability to block 5-HT receptors in the canine basilar artery, in spite of the similar and high affinity of the antagonists at 5-HT1 binding sites. These data support the contention that 5-HT receptors in the canine basilar artery are not 5-HT1 receptors as defined by ligand binding studies in brain cortical membranes. Similarity of the contractile effects of 5-HT in the rat stomach fundus and in the basilar artery coupled to the previous observations that receptors mediating 5-HT-induced contractions in the fundus were not 5-HT1, 5-HT1A, 5-HT1B or 5-HT2 led us to consider the possibility that 5-HT receptors in the canine basilar artery may resemble those in the rat stomach fundus. The affinity of several 5-HT antagonists determined in the canine basilar artery correlated extremely well (correlation coefficient = 0.96) with the affinities obtained for the same antagonists in the rat stomach fundus.(ABSTRACT TRUNCATED AT 250 WORDS)


Immortalized mouse dental papilla mesenchymal cells preserve odontoblastic phenotype and respond to bone morphogenetic protein 2.
Odontogenesis is the result of the reciprocal interactions between epithelial-mesenchymal cells leading to terminally differentiated odontoblasts. This process from dental papilla mesenchymal cells to odontoblasts is regulated by a complex signaling pathway. When isolated from the developing tooth germs, odontoblasts quickly lose their potential to maintain the odontoblast-specific phenotype. Therefore, generation of an odontoblast-like cell line would be a good surrogate model for studying the dental mesenchymal cell differentiation into odontoblasts and the molecular events of dentin formation. In this study, immortalized dental papilla mesenchymal cell lines were generated from the first mouse mandibular molars at postnatal day 3 using pSV40. These transformed cells were characterized by RT-PCR, immunohistochemistry, Western blot, and analyzed for alkaline phosphatase activity and mineralization nodule formation. One of these immortalized cell lines, iMDP-3, displayed a high proliferation rate, but retained the genotypic and phenotypic characteristics similar to primary cells as determined by expression of tooth-specific markers and demonstrated the ability to differentiate and form mineralized nodules. Furthermore, iMDP-3 cells had high transfection efficiency as well as were inducible and responded to BMP2 stimulation. We conclude that the establishment of the stable murine dental papilla mesenchymal cell line might be used for studying the mechanisms of dental cell differentiation and dentin formation.


[Neurovascular compression (conflict)]].
Since Dandy first reported vascular compression of the trigeminal nerve, the concept of neurovascular compression syndrome for trigeminal neuralgia and hemifacial spasm (HFS) has been accepted, and neurovascular decompression has been performed for this condition. The further investigations indicated that some other clinical syndromes such as glossopharyngeal neuralgia, disabling positional vertigo, tinnitus, geniculate neuarlgia, spasmodic torticolis, essential hypertension, cyclic oculomotor spasm with paresis and superior oblique myokymia also may be initiated by vascular compression of the glossopharyngeal, cochleovestibular, intermediate, accessory, oculomotor and trochlear nerves or the ventrolateral medulla oblongata. In this study several hypotheses regarding the development of cranial nerves vascular compression syndromes are presented. It is alsoemphasized the value of high-resolution magnetic resonance tomographic angiography for visualization of vascular compression. The most frequent clinical syndromes caused by vascular compressionof the cranial nerves are discussed regarding the pathogenesis, symptomes and therapy. We present our series of 124 patients with preoperative evidently positive finding of vascular compression to the trigeminal nerve (MRI). Microvascular decompression (MVD) was performed in all of them. Initial postoperative result was excellent in 110/124 (89%) patients,while in 11/124 (9%) patients the pain relief was satisfactory. In the remaining three patients MVD failed. Recurrence of pain after two years reached 19%. Complications were related to diplopia associated with transient fourth nerve dysfunction in 5 (4%) patients, facial motor dysfunction in 4 (3%) patients, transient facial hypesthesia in 27 (22%) patients and partially hearing loss in 4 (3%) patients. Cerebellar hemorrhagic infarction occurred in 1 (0.8%) patient and cerebrospinal fluid leaks appeared in two (1.6%) cases. There was no lethal outcome.


The first case of the 2015 Korean Middle East Respiratory Syndrome outbreak.
This study reviewed problems in the prevention of outbreak and spread of Middle East Respiratory Syndrome (MERS) and aimed to provide assistance in establishing policies to prevent and manage future outbreaks of novel infectious diseases of foreign origin via in-depth epidemiological investigation of the patient who initiated the MERS outbreak in Korea, 2015. Personal and phone interviews were conducted with the patient and his guardians, and his activities in Saudi Arabia were investigated with the help of the Saudi Arabian Ministry of Health. Clinical courses and test results were confirmed from the medical records. The patient visited 4 medical facilities and contacted 742 people between May 11, 2015, at symptom onset, and May 20, at admission to the National Medical Center; 28 people were infected and diagnosed with MERS thereafter. Valuable lessons learned included: (1) epidemiological knowledge on the MERS transmission pattern and medical knowledge on its clinical course; (2) improvement of epidemiological investigative methods via closed-circuit television, global positioning system tracking, and review of Health Insurance Review and Assessment Service records; (3) problems revealed in the existing preventive techniques, including early determination of the various people contacted; (4) experiences with preventive methods used for the first time in Korea, including cohort quarantine; (5) reconsideration of the management systems for infectious disease outbreaks across the country, such as this case, at the levels of central government, local government, and the public; (6) reconsideration of hospital infectious disease management systems, culture involving patient visitation, and emergency room environments.


NOX4 alleviates breast cancer cell aggressiveness by co-ordinating mitochondrial turnover through PGC1α/Drp1 axis.
Triple Negative Breast Cancer (TNBC) is a highly aggressive form of breast cancer, with few treatment options. This study investigates the complex molecular mechanism by which NADPH oxidase 4 (NOX4), a major ROS producer in mitochondria, affects the aggressiveness of luminal and triple-negative breast cancer cells (TNBCs). We found that NOX4 expression was differentially regulated in luminal and TNBC cells, with a positive correlation to their epithelial characteristics. Time dependent analysis revealed that TNBCs exhibits higher steady-state ROS levels than luminal cells, but NOX4 silencing increased ROS levels in luminal breast cancer cells and enhanced their ability to migrate and invade. In contrast, NOX4 over expression in TNBCs had the opposite effect. The mouse tail-vein experiment showed that the group injected with NOX4 silenced luminal cells had a higher number of lung metastases compared to the control group. Mechanistically, NOX4 enhanced PGC1α dependent mitochondrial biogenesis and attenuated Drp1-mediated mitochondrial fission in luminal breast cancer cells, leading to an increased mitochondrial mass and elongated mitochondrial morphology. Interestingly, NOX4 silencing increased mitochondrial ROS (mtROS) levels without affecting mitochondrial (Δψm) and cellular integrity. Inhibition of Drp1-dependent fission with Mdivi1 reversed the effect of NOX4-dependent mitochondrial biogenesis, dynamics, and migration of breast cancer cells. Our findings suggest that NOX4 expression diminishes from luminal to a triple negative state, accompanied by elevated ROS levels, which may modulate mitochondrial turnover to attain an aggressive phenotype. The study provides potential insights for targeted therapies for TNBCs.


Strong assortative mating by diet, color, size, and morphology but limited progress toward sympatric speciation in a classic example: Cameroon crater lake cichlids.
Models predict that sympatric speciation depends on restrictive parameter ranges, such as sufficiently strong disruptive selection and assortative mating, but compelling examples in nature have rarely been used to test these predictions. I measured the strength of assortative mating within a species complex of Tilapia in Lake Ejagham, Cameroon, a celebrated example of incipient sympatric adaptive radiation. This species complex is in the earliest stages of speciation: morphological and ecological divergence are incomplete, species differ primarily in breeding coloration, and introgression is common. I captured 27 mated pairs in situ and measured the diet, color, size, and morphology of each individual. I found strong assortative mating by color, size, head depth, and dietary source of benthic or pelagic prey along two independent dimensions of assortment. Thus, Ejagham Tilapia showed strong assortative mating most conducive to sympatric speciation. Nonetheless, in contrast to a morphologically bimodal Sarotherodon cichlid species pair in the lake, Ejagham Tilapia show more limited progress toward speciation, likely due to insufficient strength of disruptive selection on morphology estimated in a previous study (γ = 0.16). This supports the predicted dependence of sympatric speciation on strong assortment and strong disruptive selection by examining a potentially stalled example in nature.


Catalysis of electro-oxidation of antibiotics by nitroxyl radicals and the electrochemical sensing of vancomycin.
Quantifying drug concentrations in vivo quickly and easily is possible using electrochemical methods. The present study describes the electrochemical detection of vancomycin (VCM) and other antibiotics from the current obtained using nitroxyl radicals as electrocatalysts. Nortropine N-oxyl (NNO), which is more active than 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO), a typical nitroxyl radical compound, produced greater current values for drugs with intramolecular hydroxy groups and secondary and tertiary amines. However, because the catalytic action of NNO is inactivated by primary amines in the substrate, VCM and teicoplanin with primary amines could not be detected. TEMPO was less active than NNO but not inactivated against primary amines. Therefore, electrochemical sensing of vancomycin was done using 4-acetamido-2,2,6,6-tetramethylpiperidine 1-oxyl (A-TEMPO), which has a greater oxidation capacity than TEMPO due to its electron-withdrawing groups. As a result, the current of A-TEMPO increased in the low concentration range of VCM as compared to TEMPO. This method also was able to quantify VCM in the concentration range of 10-100 μM, which is an important concentration range for drug monitoring in blood.


Problem-service 'matching' in addiction treatment. A prospective study in 4 programs.
Our initial attempts to "match" substance-abuse patients from an employee assistance program to an optimal setting or program failed. Scientifically, we found no differential predictors of better outcomes by setting or program. From a practical perspective, it was impossible to place patients in the intended programs. This led to a second study, designed to identify specific patient problems and match professional services to those problems within each of the 4 programs. Ninety-four new patients admitted to 4 substance-abuse treatment programs were randomly assigned to standard treatment and treated in the usual manner or were assigned to "matched" services, in which patients received at least 3 professional sessions directed at their important employment, family, or psychiatric problems. Matched patients stayed in treatment longer, were more likely to complete treatment, and had better posttreatment outcomes than did the standard patients treated in the same programs. For logistical, financial, and clinical reasons, it is improbable that patients will be matched to specific types of programs. However, within any program, it is possible and practical to match appropriate services to patients' specific treatment problems. This strategy was clinically and administratively practical, attractive to patients, and responsible for a 20% to 30% increase in the effectiveness of this substance-abuse treatment system.


Patient selection for whole brain radiotherapy (WBRT) in a large lung cancer cohort: Impact of a new Dutch guideline on brain metastases.
Median survival after diagnosis of brain metastases is, depending on the Recursive Partitioning Analysis (RPA) classes, 7.1 (class I) to 2.3 months (class III). In 2011 the Dutch guideline on brain metastases was revised, advising to withhold whole brain radiotherapy (WBRT) in RPA class III. In this large retrospective study, we evaluated the guideline's use in daily practice. Data of 428 lung cancer patients undergoing WBRT for brain metastases (2004-2012) referred from three Dutch hospitals were retrospectively analyzed. Details on Karnofsky performance score (KPS), age, control of primary tumor, extracranial metastases, histology, and survival after diagnosis of brain metastases were collected. RPA class was determined using the first four items. In total 327 patients had non-small cell lung cancer (NSCLC) and 101 small cell lung cancer (SCLC). For NSCLC, 6.1%, 71.9%, and 16.2% were classified as RPA I, II, and III, respectively, and 5.8% could not be classified. For SCLC this was 8.9%, 66.3%, 14.9%, and 9.9%, respectively. Before the revised guideline was implemented, 11.3-21.3% of WBRT patients were annually classified as RPA III. In the year thereafter, this was 13.0% (p = 0.646). Median survival (95% CI) for NSCLC RPA class I, II, and III was 11.4 (9.9-12.9), 4.0 (3.4-4.7), and 1.7 (1.3-2.0) months, respectively. For SCLC this was 7.9 (4.1-11.7), 4.7 (3.3-6.1), and 1.7 (1.5-1.8) months. Although it is advised to withhold WBRT in RPA class III patients, in daily practice 11.3-21.3% of WBRT-treated patients were classified as RPA III. The new guideline did not result in a decrease. Reasons for referral of RPA III patients despite a low KPS were not found. Despite WBRT, survival of RPA III patients remains poor and this poor outcome should be stressed in practice guidelines. Therefore, better awareness amongst physicians would prevent some patients from being treated unnecessarily.


[ORBIT-NET. Discussion forum on orbitology on the internet].
A basic service in the public network "Internet" is electronic mail (e-mail). E-mail makes the participation in discussion groups possible by mailing contributions to the discussion to all members electronically. To complement the existing list of ophthalmologic discussion groups ORBIT-NET was introduced. It offers experts in research, clinic, diagnostic and therapy of orbital diseases the opportunity to make queries or present interesting casuistries and to ask for comments, differential diagnosis or advice on therapy. Other participants can be made aware of new scientific results, actual publications or meetings. For participation a computer, a modem, an Internet-Provider and special software are required. Registration is made either by e-mail or regular mail. A verification is necessary to limit the list of participants to experts. Since the introduction of ORBIT-NET on November 9th, 1996, there have been no technical problems. ORBIT-NET has been effective as a platform. The international, interdisciplinary platform ORBIT-NET is an addition to the existing ophthalmologic discussion groups. ORBIT-NET offers orbitologists an international discussion of results and diagnosis, supports further training and can give encouragement to further research.


Comparative integrated molecular analysis of intraocular medulloepitheliomas and central nervous system embryonal tumors with multilayered rosettes confirms that they are distinct nosologic entities.
Intraocular medulloepithelioma (IO MEPL) is an uncommon embryonal neuroepithelial neoplasm of the eye. These ocular neoplasms have been compared with intracranial medulloepitheliomas or other histologic variants of CNS embryonal tumor with multilayered rosettes (CNS ETMR) due to their morphological mimicry. We performed comprehensive molecular analysis to explore the histogenetic and biologic relationships between 22 IO MEPL and 68 CNS ETMR. Routinely prepared paraffin-embedded samples were assessed for genome-wide methylation profiles using the Illumina Methylation 450k BeadChip array. We identified strong cytogenetic and epigenetic differences between ocular neoplasms and CNS ETMR. None of the IO MEPL cases displayed the ETMR-specific amplification of the C19MC locus. Instead, cytogenetic analysis of the IO MEPL showed numerous copy number aberrations which involved either whole chromosomes or chromosomal arms; recurrent aberrations in these tumors affected chromosomes 1p, 4, 8 and 16p. DNA methylation patterns were also strikingly different between these two tumor entities, suggesting that they do not share common origins and biological behaviors. Comparative cluster analysis of 198 pediatric CNS tumors and 22 IO MEPL revealed a clear demarcation of the CNS ETMR and IO MEPL profiles from other CNS entities. In conclusion, although IO MEPL shares some histopathological features with CNS ETMR, they manifest striking molecular diversity at the cytogenetic and epigenetic levels. Consequently they deserve a separate nosologic designation in future tumor classifications, where CNS MEPL could be designated as a histological variant of CNS ETMR.


AmIRTEM: a functional model for training of aerobic endurance for health improvement.
In a nonstrenuous exercise, the heart rate (HR) shows a linear relationship with the maximum volume of oxygen consumption VO(2Max) and serves as an indicator of performance of the cardiovascular system. The HR replaces the %VO(2Max) in exercise program prescription to improve aerobic endurance. In order to achieve an optimal effect in an endurance training, the athlete needs to work out at an HR high enough to trigger the aerobic metabolism, while avoiding the very high HRs that bring along significant risks of myocardial infarction. The minimal and optimal base training programs, followed by stretching exercises to prevent injuries, are adequate programs to maximize benefits and minimize health risks for the cardiovascular system during single session training. In this paper, we have defined a functional model for an ambient intelligence system that monitors, evaluates, and trains the aerobic endurance. It is based on the Android operating system and the Gow Running smart shirt. The system has been evaluated during functional assessment stress testing of aerobic endurance in the Stress Physiology Laboratory (SPL) of the Technical University of Madrid. Furthermore, a voice system designed to guide the user through minimal and optimal base training programs has been evaluated. The results obtained fully confirm the model with a high correlation between the data collected by the system and the by SPL. There is also a high hit rate between training sessions of the users and the objective training functions defined in the training programs.


Evaluation of pre-hospital administration of adrenaline (epinephrine) by emergency medical services for patients with out of hospital cardiac arrest in Japan: controlled propensity matched retrospective cohort study.
To evaluate the effectiveness of pre-hospital adrenaline (epinephrine) administered by emergency medical services to patients with out of hospital cardiac arrest. Controlled propensity matched retrospective cohort study, in which pairs of patients with or without (control) adrenaline were created with a sequential risk set matching based on time dependent propensity score. Japan's nationwide registry database of patients with out of hospital cardiac arrest registered between January 2007 and December 2010. Among patients aged 15-94 with out of hospital cardiac arrest witnessed by a bystander, we created 1990 pairs of patients with and without adrenaline with an initial rhythm of ventricular fibrillation or pulseless ventricular tachycardia (VF/VT) and 9058 pairs among those with non-VF/VT. Overall and neurologically intact survival at one month or at discharge, whichever was earlier. After propensity matching, pre-hospital administration of adrenaline by emergency medical services was associated with a higher proportion of overall survival (17.0% v 13.4%; unadjusted odds ratio 1.34, 95% confidence interval 1.12 to 1.60) but not with neurologically intact survival (6.6% v 6.6%; 1.01, 0.78 to 1.30) among those with VF/VT; and higher proportions of overall survival (4.0% v 2.4%; odds ratio 1.72, 1.45 to 2.04) and neurologically intact survival (0.7% v 0.4%; 1.57, 1.04 to 2.37) among those with non-VF/VT. Pre-hospital administration of adrenaline by emergency medical services improves the long term outcome in patients with out of hospital cardiac arrest, although the absolute increase of neurologically intact survival was minimal.


Natural deoxynivalenol occurrence and genotype and chemotype determination of a field population of the Fusarium graminearum complex associated with soybean in Argentina.
Soybean (Glycine max L.), the main source of protein throughout the world, is used both as a food and a feedstuff. Currently, limited information about the occurrence of Fusarium species and mycotoxins in soybean grain and by-products is available. The aims of the present study were: (1) to identify toxigenic Fusarium species associated with soybean during crop reproductive stages; (2) to determine the occurrence of deoxynivalenol (DON) and nivalenol (NIV) in soybean seeds; (3) to determine the genotype and chemotype of selected Fg complex strains using molecular and chemical analysis, respectively; and (4) to characterize the strains using AFLP(s) markers. One soybean field located at Córdoba Province, Argentina, was monitored and samples of soybean tissue were harvested at three reproductive stages: flowering (R2), full seed (R6) and full maturity (R8). A total of 389 Fusarium strains F. equiseti (40%) was the most frequently species recovered followed by F. semitectum (27%) and F. graminearum (Fg) (11%). From the 40 soybean samples analysed, only two presented detectable DON levels. Based on DON occurrence on soybean seeds at ripening stages, the toxigenic ability of Fg complex strains isolated from soybean seeds, pods and flowers were analysed. The trichothecene genotype was determined by a multiplex PCR using primers based on Tri3, Tri5 and Tri7 toxin genes and then the chemotype was verified by chemical analysis. Most Fg complex strains showed 15-ADON genotype and five strains presented a DON/NIV; these also produced both toxins under in vitro culture. Neither the NIV nor the 3-ADON genotypes were detected among the members of the population evaluated. All the 15-ADON genotype strains were characterized as F. graminearum sensu stricto (lineage 7), while the strains presented a DON/NIV genotype were characterized as F. meridionale (lineage 2). The present study contributes new information on the occurrence of Fusarium species and trichothecenes toxins on soybean at the pre-harvest stages. Also, this is the first report on the chemotype, genotype and lineages among Fg complex isolated from soybean.


Stepwise Evolution Improves Identification of Diverse Peptides Binding to a Protein Target.
Considerable efforts have been made to develop technologies for selection of peptidic molecules that act as substrates or binders to a protein of interest. Here we demonstrate the combination of rational peptide array library design, parallel screening and stepwise evolution, to discover novel peptide hotspots. These hotspots can be systematically evolved to create high-affinity, high-specificity binding peptides to a protein target in a reproducible and digitally controlled process. The method can be applied to synthesize both linear and cyclic peptides, as well as peptides composed of natural and non-natural amino acid analogs, thereby enabling screens in a much diverse chemical space. We apply this method to stepwise evolve peptide binders to streptavidin, a protein studied for over two decades and report novel peptides that mimic key interactions of biotin to streptavidin.


Varenicline in the treatment of tobacco dependence.
Varenicline, a partial agonist of alpha(4)beta(2) nicotinic acetylcholine receptors, is the most recently approved drug for smoking cessation. This paper reviews the outcomes of Phase 2 and Phase 3 clinical trials that assess the efficacy of varenicline in comparison to placebo and other smoking cessation pharmacotherapies, ie, sustained-release bupropion (bupropion SR) and nicotine transdermal patch. Varenicline has higher abstinence rates than placebo and the alternative active treatments at the end of standard regimen treatment periods. Significantly higher abstinence rates were also found with varenicline in comparison to both placebo and bupropion SR at the end of a 40-week non-treatment follow-up period. Varenicline typically tripled the abstinence rates compared with placebo. In addition, varenicline reduced craving and withdrawal symptoms as well as some of the positive experiences associated with smoking to a greater extent than placebo, bupropion SR, and nicotine replacement therapy (NRT). These findings are consistent with the proposed agonist/antagonist effects of varenicline. Preliminary studies assessing individual variables such as smoking dependency level and smoking reinforcement types provide justification to examine further the effects of varenicline according to these individual factors. Outcomes from such research could improve our understanding of varenicline's mechanism of action and could ultimately help clinicians to develop individualized smoking cessation programs. Also, given varenicline's ability to reduce the reward from smoking, it might be helpful to use it before cessation to motivate or prepare smokers for a quit attempt.


Synthesis and Characterization of Paclitaxel-Loaded PEGylated Liposomes by the Microfluidics Method.
For cancer therapy, paclitaxel (PX) possesses several limitations, including limited solubility and untargeted effects. Loading PX into nanoliposomes to enhance PX solubility and target their delivery as a drug delivery system has the potential to overcome these limitations. Over the other conventional method to prepare liposomes, a microfluidic system is used to formulate PX-loaded PEGylated liposomes. The impact of changing the flow rate ratio (FRR) between the aqueous and lipid phases on the particle size and polydispersity index (PDI) is investigated. Moreover, the effect of changing the polyethylene glycol (PEG) lipid ratio on the particle size, PDI, stability, encapsulation efficiency % (EE %), and release profile is studied. The physicochemical characteristics of the obtained formulation were analyzed by dynamic light scattering, FTIR spectroscopy, and AFM. This work aims to use microfluidic technology to produce PEGylated PX-loaded liposomes with a diameter of <200 nm, low PDI < 0.25 high homogeneity, and viable 28 day stability. The results show a significant impact of FRR and PEG lipid ratio on the empty liposomes' physicochemical characteristics. Among the prepared formulations, two formulations produce size-controlled, low PDI, and stable liposomes, which make them preferable for PX encapsulation. The average EE % was >90% for both formulations, and the variation in the PEG lipid ratio affected the EE % slightly; a high packing for PX was reported at different drug concentrations. A variation in the release profiles was notified for the different PEG lipid ratios.


Challenges faced in recruiting patients from primary care practices into a physical activity intervention trial. Activity Counseling Trial Research Group.
Special challenges are encountered when clinical trial recruitment targets a physician practice-based population, as opposed to recruiting from the community. Since most published information about recruitment has focused on the latter group, summation of successful primary-care-based recruitment strategies could prove useful for future trials recruiting from this population. The Activity Counseling Trial (ACT) is a multicenter, randomized clinical trial that evaluated approaches to primary care-based interventions to increase physical activity in sedentary adults 35-75 years of age. Fifty-four clinicians from eight practices recruited 874 participants from three U.S. sites. Recruitment challenges that related, in great part, to the primary care setting included: (1) focusing on patients from ACT physician practices who had regularly scheduled or intend-to-schedule appointments within the next year; (2) placing trial staff in the clinical offices for recruitment purposes; and (3) placing trial interventionists in the physicians' offices. Other challenges were related to recruitment of minorities and men. Patient mailing yielded 43.4% of all randomized participants, followed by office-based questionnaires (32.5%) and direct telephone contact (21.6%). Based on a retrospective cost-effective analysis (indirect costs excluded), the self-administered office-based questionnaire was the least costly strategy for one site ($14/randomized participant), followed by patient mailing at another site ($58). The direct telephone contact method utilized at one site serving primarily a minority population yielded a per randomized participant cost of $80. Recruitment of clinical trial participants from practice-based populations requires modification of the strategies used to recruit from the community. Multiple strategies should be employed, followed closely for their respective yields, and adapted as needed.


Influence of molecular weight of DNA on the determination of anti-DNA antibodies in systemic lupus erythematosus (SLE) sera by radioimmunoassay.
Using a radioimmunoassay (RIA) based on the Farr technique with radioactively labeled 3-H-DNA for quantitative measurements of anti-DNA antibodies in sera of patients with systemic lupus erythematosus (SLE), the influence of molecular weight of DNA (ranging from 0.1 times 10-6 to 22.0 times 10-6 daltons) on binding and precipitation in this system has been investigated. Comparing our results with mathematical models it follows that one antibody molecule is fixed on the average to a statistical DNA segment of 2 times 10-6 to 4 times 10-6 daltons. Furthermore binding capacity of the DNA was found to be independent of the molecular weight, as demonstrated in a double label experiment using 14-C and 3-H-labeled DNA of different size. However, the amount of radioactivity precipitated was found to depend on the molecular weight of the labeled DNA following a non-linear function. It was calculated that a minimal ratio of fixed antibody molecules per a certain size of DNA was necessary for precipitation. The mathematical treatment of the observed non-linear precipitation dependence will be discussed using various statistical models. Our results indicate that the quantitative measurements of anti-DNA antibodies with the Farr technique e.g. for diagnosis and control of SLE in clinical immunology is highly dependent on the molecular weight of the labeled DNA used in the assay system and reliable results are only obtained with DNA of a sufficiently high molecular weight.


Stressors and common mental disorder in informal carers--an analysis of the English Adult Psychiatric Morbidity Survey 2007.
This study investigates potential explanations of the association between caring and common mental disorder, using the English Adult Psychiatric Morbidity Survey 2007. We examined whether carers are more exposed to other stressors additional to caring--such as domestic violence and debt--and if so whether this explains their elevated rates of mental disorder. We analysed differences between carers and non-carers in common mental disorders (CMD), suicidal thoughts, suicidal attempts, recent stressors, social support, and social participation. We used multivariate models to investigate whether differences between carers and non-carers in identifiable stressors and supports explained the association between caring and CMD, as measured by the revised Clinical Interview Schedule. The prevalence of CMD (OR=1.64 95% CI 1.37-1.97), suicidal thoughts in the last week (OR=2.71 95% CI 1.31-5.62) and fatigue (OR=1.33 95% CI 1.14-1.54) was increased in carers. However, caring remained independently associated with CMD (OR=1.58 1.30-1.91) after adjustment for other stressors and social support. Thus caring itself is associated with increased risk of CMD that is not explained by other identified social stressors. Carers should be recognized as being at increased risk of CMD independent of the other life stressors they have to deal with. Interventions aimed at a direct reduction of the stressfulness of caring are indicated. However, carers also reported higher rates of debt problems and domestic violence and perceived social support was slightly lower in carers than in non-carers. So carers are also more likely to experience stressors other than caring and it is likely that they will need support not only aimed at their caring role, but also at other aspects of their lives.


Children's exposure to food advertising: the impact of statutory restrictions.
Evidence demonstrating links between exposure to unhealthy food marketing, poor eating behaviours and paediatric obesity has led to calls for regulatory change in many countries, including the UK. However no official monitoring system exists to inform international debate on food advertising policy. This study systematically explores food advertising on UK television in 2010 (post-regulation) and compare this to 2008 (mid-regulation) to assess if food adverts improved in nutritional quality after implementation of regulations. Television was recorded between 6 a.m. and 10 p.m. for one weekday and one weekend day during 6 months of 2010 across 13 commercial television channels popular with children. These data were directly compared with previously published data for 2008. Food and beverages were the third most frequently advertised product type (11.9% of all ads), a decrease of 0.9% from 2008 (12.8%). Non-core food commercials decreased (down 2.2-53.8%) and core food advertising increased (up 0.5-18.6%). Fast food items were the third most frequently advertised food product (15.4%, up 3.5% from 2008). During peak children's viewing times, 17.0% of all commercials were for food, an increase of 4.7% from non-peak children's viewing times and fewer core (-0.9%) and more non-core (+0.5%) foods were advertised at these times. Despite statutory regulation, frequency and balance of food commercials (core, non-core and miscellaneous) remained relatively static over the 2 years. Children are still exposed to high amounts of unhealthy food advertising on television. Continued monitoring of television food advertising remains crucial and policymakers should examine the comparative efficacy of other restrictions.


Deep learning downscaled high-resolution daily near surface meteorological datasets over East Asia.
U-Net, a deep-learning convolutional neural network, is used to downscale coarse meteorological data. Based on 19 models from the Coupled Model Intercomparison Project Phase 6 and the Multi-Source Weather (MSWX) dataset, bias correction and UNet downscaling approaches are used to develop high resolution dataset over the East Asian region, referred to as Climate Change for East Asia with Bias corrected UNet Dataset (CLIMEA-BCUD). CLIMEA-BCUD provides nine meteorological variables including 2-m air temperature, 2-m daily maximum air temperature, 2-m daily minimum air temperature, precipitation, 10-m wind speed, 2-m relative humidity, 2-m specific humidity, downward shortwave radiation and downward longwave radiation with 0.1° horizontal resolution at daily intervals over the historical period of 1950-2014 and three future scenarios (SSP1-2.6, SSP2-4.5 and SSP5-8.5) of 2015-2100. Validation against MSWX indicates that CLIMEA-BCUD shows reasonable performance in terms of climatology, and it is capable of simulating seasonal cycles and future changes well. It is suggested that CLIMEA-BCUD can promote the application of deep learning in climate research in the areas of climate change, hydrology, etc.


[Retinotopic organization of the human visual cortex: a 3T fMRI study].
INTRODUCTION. We used high-field (3T) functional magnetic resonance imaging (fMRI) to map the retinotopic organization of human cortical areas. Retinotopic maps were reconstructed using existing mapping techniques. Stimuli were made of a rotating wedge stimulus, which provided angular coordinate maps, and an expanding or contracting ring, which provided eccentricity coordinate maps. Stimuli consisted of a grey background alternating with a flickering checkerboard. A Brucker 3T scanner equipped with a head coil and a custom optical system was used to acquire sets of echoplanar images of 20 occipital coronal slices within a RT of 2.111 ms and an 8 mm3 voxel resolution. Surface models of each subject's occipital lobes were constructed using the Brainvisa software from a sagittal T1-weighted image with a 1 mm3 voxel resolution. The cortical models were then inflated to obtain unfolded surfaces. Statistical analyses of the functional data were made under SPM99, and the response amplitudes were finally assigned to the cortical reconstructed surfaces. We identified boundaries between different early visual areas (V1, V2, V3) using eccentricity and polar angle retinotopic maps and detection of reversals in the representation of the polar angle. Both complete maps and reversals corresponding to the V1/V2 borders were clearly visible with a single recording session. Also, we were able to compare data from subjects across various fMRI acquisitions and found that there was a strong correlation between maps acquired at different sessions for the same subject. We developed a quick (<40 min) retinotopic cortical area mapping method at 3T, which makes it possible to study the cortical remapping in patients with retinal scotomas.


The CCAAT/enhancer-binding protein-alpha is expressed in the germinal layer of the growth plate: colocalisation with the growth hormone receptor.
The transcription factor C/EBP alpha, a member of the CCAAT/enhancer-binding protein family, is highly expressed in the liver and in adipose tissue. The aim of this study was to determine if C/EBP alpha is expressed in rat growth cartilage. The expression pattern of C/EBP alpha in monolayer-cultured growth plate chondrocytes was similar to that of C/EBP alpha during hepatocyte and preadipocyte differentiation. Immunohistochemistry with a polyclonal antibody for C/EBP alpha revealed that the C/EBP alpha protein is present in the perichondrial ring, in the germinal layer of the growth plate and on the surface of the articular cartilage. The growth hormone (GH) receptor has a similar distribution in the rat tibial growth plate, and hypophysectomised rats were used to investigate a possible connection between C/EBP alpha and GH. C/EBP alpha mRNA levels were decreased in rib cartilage after hypophysectomy. However, GH treatment did not counteract this effect, indicating that other pituitary hormones regulate the C/EBP alpha mRNA levels in growth plate cartilage. We thus demonstrate, for the first time, that C/EBP alpha is expressed in cartilage. The finding that C/EBP alpha, like the GH receptor, is predominantly expressed in stem cell areas of the rat growth plate indicates a possible functional role for C/EBP alpha during early chondrogenic differentiation.


Classification of small cell lung cancer and pulmonary carcinoid by gene expression profiles.
Small cell lung cancer is a common type of lung cancer that is generally classified within the spectrum of neuroendocrine lung neoplasms. Using high-density cDNA arrays, we profiled gene expression of small cell lung cancers and compared these expression profiles to those of normal bronchial epithelial cells and pulmonary carcinoids, which are classified as benign neuroendocrine tumors. We found the overall expression profiles of two small cell lung cancer cell lines, two microdissected tissue samples of primary small cell lung cancer, and cultured bronchial epithelial cells to be relatively similar to one another, with an average Pearson correlation coefficient for these comparisons of 0.63. However, we found the expression profiles of small cell lung cancers (and bronchial epithelial cells) to be surprisingly dissimilar to those of two samples of pulmonary carcinoid tumors, with an average correlation coefficient for these comparisons of 0.20. We then compared the pulmonary carcinoid expression profiles to those of two samples of infiltrating astrocytic brain cancers (oligodendroglioma and high-grade astrocytoma) and found similarity of gene expression among these four samples (average correlation coefficient, 0.57). These gene expression profiles suggest that small cell lung cancers are closely related to (and possibly derived from) epithelial cells, and that pulmonary carcinoids are related to neural crest-derived brain tumors. More generally, our results suggest that broad profiles of gene expression may reveal similarities and differences between tumors that are not apparent by traditional morphological criteria.


Duration of immunity to experimental infection with bovine respiratory syncytial virus following intranasal vaccination of young passively immune calves.
To determine whether a combination modified-live bovine respiratory syncytial virus (BRSV) vaccine could stimulate protective immunity in young BRSV-seropositive calves following intranasal administration and determine the duration of clinical immunity. Controlled challenge study. Animals-84 dairy calves (3 to 11 days old). Responses to BRSV challenge of seronegative calves vaccinated under licensing trial conditions were compared with those of seropositive calves 2 times after vaccination. In experiment 1, young BRSV-seronegative calves were vaccinated intranasally with a minimum immunizing dose of BRSV and challenged with BRSV approximately 7 weeks later. In experiments 2 and 3, young BRSV-seropositive calves were vaccinated intranasally with a commercially available combination modified-live virus vaccine containing the commercial dose of the BRSV fraction and challenged with BRSV 9 weeks or approximately 14 weeks later, respectively. In experiments 1 and 2, BRSV-vaccinated calves had significantly higher Pao2, significantly fewer lung lesions, and significantly lower mortality rate than did unvaccinated calves subsequent to BRSV challenge. In contrast, in experiment 3, there were no differences in Pao2, lung lesions, or mortality rate between vaccinated and control calves after BRSV challenge approximately 14 weeks after vaccination. Protected calves in experiment 1 consistently had significant anamnestic mucosal and systemic antibody responses after challenge, whereas in experiments 2 and 3, antibody responses after challenge were more variable. A combination BRSV vaccine administered intranasally to young calves induced protective immunity in the presence of maternal antibodies. The duration of immune responses induced by intranasal vaccination was short (≤ 4 months). Boosting immunity iatrogenically, or by natural exposure, is probably required to obtain optimal responses to neonatal intranasal vaccination.


Oral bacteria in biofilms exhibit slow reactivation from nutrient deprivation.
The ability of oral bacteria to enter a non-growing state is believed to be an important mechanism for survival in the starved micro-environments of the oral cavity. In this study, we examined the reactivation of nutrient-deprived cells of two oral bacteria in biofilms, Streptococcus anginosus and Lactobacillus salivarius. Non-growing cells were generated by incubation in 10 mM potassium phosphate buffer for 24 h and the results were compared to those of planktonic cultures. When both types of cells were shifted from a rich, peptone-yeast extract-glucose (PYG) medium to buffer for 24 h, dehydrogenase and esterase activity measured by the fluorescent dyes 5-cyano-2,3-ditolyl-tetrazolium chloride (CTC) and fluorescein diacetate (FDA), respectively, was absent in both species. However, the membranes of the vast majority of nutrient-deprived cells remained intact as assessed by LIVE/DEAD staining. Metabolic reactivation of the nutrient-deprived biofilm cells was not observed for at least 48 h following addition of fresh PYG medium, whereas the non-growing planktonic cultures of the same two strains were in rapid growth in less than 2 h. At 72 h, the S. anginosus biofilm cells had recovered 78 % of the dehydrogenase activity and 61 % of the esterase activity and the biomass mm(-2) had increased by 30-35 %. With L. salivarius at 72 h, the biofilms had recovered 56 % and 75 % of dehydrogenase and esterase activity, respectively. Reactivation of both species in biofilms was enhanced by removal of glucose from PYG, and S. anginosus cells were particularly responsive to yeast extract (YE) medium. The data suggest that the low reactivity of non-growing biofilm cells to the introduction of fresh nutrients may be a survival strategy employed by micro-organisms in the oral cavity.


Why do the sick not utilise health care? The case of Zambia.
When ill the individual faces the options of seeking health care, using self-medication or doing nothing. In an economic perspective, an individual's propensity to utilise health care is determined by the costs of utilisation and the perceived benefits of health care. The propensity to utilise health care may hence be expected to vary between individuals. In this paper we attempt on the one hand to determine what factors influence sick individuals' propensity to seek health care at a health facility or use self-medication (or do nothing), and on the other hand attempt to determine the factors that influence the magnitude of their expenditures for health care, in particular what other factors than just health status influence utilisation. For the empirical analysis, data, covering 9700 individuals, from the 1998 Living Conditions Monitoring Survey (LCMS) is used. We use a Multinomial Logit selection model to estimate the equation, which allows us to analyse health-care utilisation through two separate processes, the decision to seek care and the magnitude of expenditures incurred. In general, we find that the individuals are influenced by income, insurance, type of illness and access variables such as distance and owning a vehicle.


Location of penetration and metabolic barriers to levobunolol in the corneal epithelium of the pigmented rabbit.
The objective of this study was to determine which of the five or six corneal epithelial layers was rate-limiting in the corneal penetration and metabolism of levobunolol in the pigmented rabbit. Corneal penetration and metabolism were evaluated using the isolated cornea in the modified Ussing chamber. Levobunolol and its metabolite, dihydrolevobunolol, were assayed by reversed phase high-performance liquid chromatography using spectrophotometric detection. EDTA (0.1 and 0.5%) and benzalkonium chloride (0.005-0.05%) were used to disrupt the integrity of the corneal epithelial layers. EDTA, which loosened the tight junctions between the superficial corneal epithelial cells, reduced both the transcorneal flux and metabolism of levobunolol. In contrast, benzalkonium chloride, which disrupted the integrity of the outermost corneal epithelial layers, enhanced the transcorneal levobunolol flux while reducing its extent of metabolism. The extent of enhancement in transcorneal flux afforded by 0.025% benzalkonium chloride was comparable to that seen in the deepithelized cornea. Within 5 min of contact by the corneal epithelium with this preservative, the ratio of dihydrolevobunolol concentration on the endothelial to the epithelial side was reduced by two-thirds. Although direct confirmation is required, the above findings are consistent with the hypothesis that the rate-limiting layer to corneal penetration of levobunolol resides in the outermost two to three layers of the corneal epithelium, whereas the metabolic barrier resides in deeper lying regions.


Oscillations by minimal bacterial suicide circuits reveal hidden facets of host-circuit physiology.
Synthetic biology seeks to enable programmed control of cellular behavior though engineered biological systems. These systems typically consist of synthetic circuits that function inside, and interact with, complex host cells possessing pre-existing metabolic and regulatory networks. Nevertheless, while designing systems, a simple well-defined interface between the synthetic gene circuit and the host is frequently assumed. We describe the generation of robust but unexpected oscillations in the densities of bacterium Escherichia coli populations by simple synthetic suicide circuits containing quorum components and a lysis gene. Contrary to design expectations, oscillations required neither the quorum sensing genes (luxR and luxI) nor known regulatory elements in the P(luxI) promoter. Instead, oscillations were likely due to density-dependent plasmid amplification that established a population-level negative feedback. A mathematical model based on this mechanism captures the key characteristics of oscillations, and model predictions regarding perturbations to plasmid amplification were experimentally validated. Our results underscore the importance of plasmid copy number and potential impact of "hidden interactions" on the behavior of engineered gene circuits - a major challenge for standardizing biological parts. As synthetic biology grows as a discipline, increasing value may be derived from tools that enable the assessment of parts in their final context.


Biophysical properties of phenyl succinic acid derivatised hyaluronic acid.
Modification of hyaluronic acid (HA) with aryl succinic anhydrides results in new biomedical properties of HA as compared to non-modified HA, such as more efficient skin penetration, stronger binding to the skin, and the ability to blend with hydrophobic materials. In the present study, hyaluronic acid has been derivatised with the anhydride form of phenyl succinic acid (PheSA). The fluorescence of PheSA was efficiently quenched by the HA matrix. HA also acted as a singlet oxygen scavenger. Fluorescence lifetime(s) of PheSA in solution and when attached to the HA matrix has been monitored with ps resolved streak camera technology. Structural and fluorescence properties changes induced on HA-PheSA due to the presence of singlet oxygen were monitored using static light scattering (SLS), steady state fluorescence and ps time resolved fluorescence studies. SLS studies provided insight into the depolymerisation kinetics of PheSA derivatised HA matrix in the presence of singlet oxygen. Time resolved fluorescence studies grave insight into the dynamics of the reaction mechanisms induced on HA-PheSA by singlet oxygen. These studies provided insight into the medical relevance of PheSA derivatised HA: its capacity of scavenging singlet oxygen and of quenching PheSA fluorescence. These studies revealed that HA-PheSA is a strong quencher of electronic excited state PheSA and acts as a scavenger of singlet oxygen, thus medical applications of this derivatised form of HA may protect tissues and organs, such as skin, against reactive oxygen species damage.


Small bowel adaptation and its regulation.
Since the subject of intestinal adaptation was last reviewed (16, 20, 97), there have been relatively few major advances but many useful minor additions and extensions which have helped to consolidate our knowledge of the field. The aim of this chapter is to summarise the results of a series of experiments which build up to our present state of knowledge. In doing so, the results of relatively old studies carried out some 15 years ago are briefly reviewed since they provide an essential background for, our current work. However, the article concentrates mainly on the new developments and in discussing these, areas of doubt and controversy are emphasised.


Effect of administered potassium on the renin-aldosterone axis in young blacks compared with whites.
We had observed previously that the aldosterone excretion rate and plasma aldosterone concentration were lower for black children than they were for white children. We did not know whether this was secondary to a lower intake of potassium or to suppression of the renin-angiotensin system in blacks. To test the hypothesis that the secretion of aldosterone in response to potassium would be different in blacks than in a control group of whites. Black and white subjects were selected on the basis of their having aldosterone excretion rates that were in the lowest quartile for the entire original cohort. Since the blacks typically had lower aldosterone excretion rates than did the whites, the black participants were represented primarily by those with average rates of aldosterone production among blacks, whereas the whites were represented by those with the lowest aldosterone production rates among whites. The protocol consisted of a placebo-controlled, randomized cross-over study design. Twelve blacks and 12 whites, aged 14.1 +/- 1.6 (mean +/- SD) and 15.4 +/- 2.1 years, respectively, were allocated randomly to double-blind treatment either with placebo or with 40 mmol/day potassium chloride for 7 days and then the alternate treatment Measurements of the plasma renin activity (PRA), plasma aldosterone concentration, and urinary aldosterone excretion were performed in an inpatient research unit at the end of the treatment. The blood pressure was monitored for 24 h. Treatment with potassium increased the plasma aldosterone concentration (P = 0.0006) and the urinary excretion of aldosterone (P = 0.0002) significantly both for blacks and for whites. There was no significant racial difference in the response to potassium. The PRA was overall 1.605-fold lower in the blacks than it was in the whites (P = 0.0124). The lowest PRA levels, such as those in the blacks when they were supine, tended to be increased with the potassium treatment. The blood pressure did not change significantly with the potassium supplement for either racial group. After we had supplemented the intake of potassium, aldosterone production increased in the blacks and in the control group of whites to the same extent The potassium treatment appeared to increase lower PRA levels. A lower intake of potassium could at least partially account for the suppression of the renin-aldosterone system in blacks.


Transcriptome meta-analysis reveals a central role for sex steroids in the degeneration of hippocampal neurons in Alzheimer's disease.
Alzheimer's disease is the most prevalent form of dementia. While a number of transcriptomic studies have been performed on the brains of Alzheimer's specimens, no clear picture has emerged on the basis of neuronal transcriptional alterations linked to the disease. Therefore we performed a meta-analysis of studies comparing hippocampal neurons in Alzheimer's disease to controls. Homeostatic processes, encompassing control of gene expression, apoptosis, and protein synthesis, were identified as disrupted during Alzheimer's disease. Focusing on the genes carrying out these functions, a protein-protein interaction network was produced for graph theory and cluster exploration. This approach identified the androgen and estrogen receptors as key components and regulators of the disrupted homeostatic processes. Our systems biology approach was able to identify the importance of the androgen and estrogen receptors in not only homeostatic cellular processes but also the role of other highly central genes in Alzheimer's neuronal dysfunction. This is important due to the controversies and current work concerning hormone replacement therapy in postmenopausal women, and possibly men, as preventative approaches to ward off this neurodegenerative disorder.


Ionosphere of venus: first observations of day-night variations of the ion composition.
The Bennett radio-frequency ion mass spectrometer on the Pioneer Venus orbiter is returning the first direct composition evidence of the processes responsible for the formation and maintenance of the nightside ionosphere. Early results from predusk through the nightside in the solar zenith angle range 63 degrees (dusk) to 120 degrees (dawn) reveal that, as on the dayside, the lower nightside ionosphere consists of F(1)and F(2) layers dominated by O(2)(+) and O(+), respectively. Also like the dayside, the nightside composition includes distributions of NO(+), C(+), N(+), H(+), He(+), CO(2)(+), and 28(+) (a combination of CO(+) and N(2)(+)). The surprising abundance of the nightside ionosphere appears to be maintained by the transport of O(+) from the dayside, leading also to the formation of O(2)(+) through charge exchange with CO(2). Above the exobase, the upper nightside ionosphere exhibits dramatic variability in apparent response to variations in the solar wind and interplanetary magnetic field, with the ionopause extending to several thousand kilometers on one orbit, followed by the complete rertnoval of thermal ions to altitudes below 200 kilometers on the succeeding orbit, 24 hours later. In the upper ionosphere, considerable structure is evident in many of the nightside ion profiles. Also evident are horizontal ion drifts with velocities up to the order of 1 kilometer per second. Whereas the duskside ionopause is dominated by O(+) H(+) dominates the topside on the dawnside of the antisolar point, indicating two separate regions for ion depletion in the magnetic tail regions.


When plants produce not enough or at all: metabolic engineering of flavonoids in microbial hosts.
As a result of the discovery that flavonoids are directly or indirectly connected to health, flavonoid metabolism and its fascinating molecules that are natural products in plants, have attracted the attention of both the industry and researchers involved in plant science, nutrition, bio/chemistry, chemical bioengineering, pharmacy, medicine, etc. Subsequently, in the past few years, flavonoids became a top story in the pharmaceutical industry, which is continually seeking novel ways to produce safe and efficient drugs. Microbial cell cultures can act as workhorse bio-factories by offering their metabolic machinery for the purpose of optimizing the conditions and increasing the productivity of a selective flavonoid. Furthermore, metabolic engineering methodology is used to reinforce what nature does best by correcting the inadequacies and dead-ends of a metabolic pathway. Combinatorial biosynthesis techniques led to the discovery of novel ways of producing natural and even unnatural plant flavonoids, while, in addition, metabolic engineering provided the industry with the opportunity to invest in synthetic biology in order to overcome the currently existing restricted diversification and productivity issues in synthetic chemistry protocols. In this review, is presented an update on the rationalized approaches to the production of natural or unnatural flavonoids through biotechnology, analyzing the significance of combinatorial biosynthesis of agricultural/pharmaceutical compounds produced in heterologous organisms. Also mentioned are strategies and achievements that have so far thrived in the area of synthetic biology, with an emphasis on metabolic engineering targeting the cellular optimization of microorganisms and plants that produce flavonoids, while stressing the advances in flux dynamic control and optimization. Finally, the involvement of the rapidly increasing numbers of assembled genomes that contribute to the gene- or pathway-mining in order to identify the gene(s) responsible for producing species-specific secondary metabolites is also considered herein.


Characterizing the research mentorship experience of genetic counseling students.
The Accreditation Council for Genetic Counseling's Practice-Based Competencies include research-related skills, which are taught in master's level genetic counseling programs through didactic coursework and completion of mentored research experiences. It is known that research mentors can impact student work environments, create positive perceptions of the research process, and increase students' likelihood of future involvement in research. However, few studies have characterized the experiences of GC students in receiving research mentorship. It is crucial to understand these experiences from student perspectives to better inform stakeholders about factors that impact mentorship. Using a mixed-methods approach, this study explored GC students' experiences receiving research mentorship and their thoughts regarding the successful qualities of research mentors. GC students (N = 165) who graduated between 2019 and 2022 responded to an online survey measuring the mentorship relationship, defined by the Advisory Working Alliance Inventory (AWAI). On average, participants scored 3.96/5 on the AWAI, where higher scores indicate stronger working alliances. When asked to describe their overall research experience in three words, 75.7% of participants used at least one negatively connotated descriptor. Thematic analysis of semi-structured interviews obtained via purposive sampling of highest and lowest scoring participants on the AWAI (N = 14) revealed the following five themes related to successful qualities of a research mentor: (1) communication; (2) rapport building and relationship; (3) engagement and guidance; (4) expertise and connections; and (5) mentors with different roles. Of note, many of these qualities are foundational skills in genetic counseling. Thus, genetic counselors who may be strong in these areas who do not identify as "researchers" ought to consider becoming a research committee member. Additionally, education programs could consider implementing research committee member evaluations and/or student research self-efficacy surveys to evaluate how these relationships may be shaping research experiences for students within their program.


[Volume replacement therapy; what is the solution?].
2 types of infusion solutions are used for volume replacement: crystalline fluids (such as NaCl 0.9% and lactated Ringer's solution) and colloidal fluids made of hydroxyethyl cellulose, albumin or gelatine. The choice of fluids used appears to be determined by the personal preference of the physician or the department. Infusion of colloidal solutions results in rapid recovery of the circulating volume but can cause anaphylaxis, renal insufficiency and an increased bleeding tendency. The use of hydroxyethyl cellulose (HEC) is associated with higher mortality and renal impairment, and is therefore not very justifiable. Albumin-based infusions appear to be predominantly indicated for septic patients with hypoalbuminaemia. Gelatin-based infusion fluids have not yet been extensively studied. The balanced lactated Ringer's solution, the composition of which is closer to plasma than that of NaCl 0.9%, is being used with ever-increasing frequency. Lactated Ringer's infusion solution does not cause hyperchloremic acidosis and probably less often leads to renal insufficiency than when NaCl 0.9% is infused.


Accurate determination of the layer thickness of a multilayer polymer film by non-invasive multivariate confocal Raman microscopy.
Plastic films of multiple layers are widely used in packaging. While a detailed spatially resolving analysis is highly relevant, the currently used approaches are either tedious or lack spatial resolution. An advanced method of confocal Raman microscopy was therefore developed in this work, using a water immersion objective combined with multivariate data analysis and ray tracing models for analysing a commercial-grade five-layer plastic film. The water immersion objective and ray tracing models are able to reduce the refraction induced artefacts in depth profiling and ensure a correct and accurate interpretation of each layer thickness. The multivariate data analysis can distinguish each layer without prior knowledge of the sample and unique markers of each composition. Finally, the resulting thicknesses of the film layers could be successfully compared to complementary experimental results. In conclusion, each layer thickness of a multilayer polymer film and its chemical composition could be measured accurately and non-invasively without sample preparation.


[Chinese expert consensus on neoadjuvant therapy for hepatocellular carcinoma (2023 edition)].
Recurrence of hepatocellular carcinoma (HCC) after surgery is a major factor affecting the efficacy of the treatment of patients. Neoadjuvant treatment is an effective therapeutic method to reduce postoperative recurrence and prolong patient survival. However,there is no generally accepted neoadjuvant treatment regimen that has been proven to be effective so far. Recently,with the progress in systemic antitumor therapies,represented by targeted molecular agents and immune checkpoint inhibitors,and the improvement in local regional therapies,these treatment approaches have shown promising efficacy and safety in the field of neoadjuvant treatment for HCC. Under the organizational leadership of Committee of Digestive Surgery of Chinese Research Hospital Association and Committee of Liver Cancer of Chinese Anti-Cancer Association,Alliance of Chinese Expert Consensus on Neoadjuvant Treatment for Hepatocellular Carcinoma has discussed and revised several times and finally formulated the Chinese expert consensus on neoadjuvant treatment for hepatocellular carcinoma (2023 Edition). This consensus aimed to review the Chinese characteristics of the diagnosis and treatment of HCC,to provide specific guidance and suggestions for preoperative treatment strategies for HCC,and further promote the management of the clinical pathway for neoadjuvant treatment of HCC.


Medical students, spirituality and religiosity--results from the multicenter study SBRAME.
To evaluate the relationship between spirituality/religiosity (S/R) and the attitudes, beliefs and experiences of medical students in Brazil with respect to S/R in their undergraduate training and clinical practice. SBRAME (Spirituality and Brazilian Medical Education) is a multicenter study involving 12 Brazilian medical schools with 5950 medical students (MS). Participants completed a questionnaire that collected information on socio-demographic data and S/R in their undergraduate training and practice. Of all MS, 3630 participated in the survey (61.0%). The sample was 53.8% women and the mean age was 22.5 years. The majority of MS believed that spirituality has an impact on patients' health (71.2%) and that this impact was positive (68.2%). The majority also wanted to address S/R in their clinical practice (58.0%) and considered it relevant (75.3%), although nearly one-half (48.7%) felt unprepared to do so. Concerning their training, most MS reported that they had never participated in a "spirituality and health" activity (81.0%) and that their medical instructors had never or rarely addressed this issue (78.3%). The majority also believed that they should be prepared to address spiritual issues related to the health of their patients (61.6%) and that this content should be included in the medical curriculum (62.6%). There is a large gap between MS attitudes and expectations and the S/R training that they are receiving during their undergraduate training. The majority of MS surveyed believe that patients should have their beliefs addressed and that these beliefs could have important effects on their health and the doctor-patient relationship. These results should stimulate discussion about the place that S/R training should have in the medical curriculum.


Human liver and conjugation of catecholamines.
To investigate the role of the liver in conjugation of catecholamines we measured the concentrations of free and conjugated norepinephrine, epinephrine, and dopamine in plasma of patients with severe liver disease who were undergoing liver transplantation. Comparisons were made with catecholamine levels in plasma of euhepatic patients who were undergoing abdominal aortic aneurysmectomy. We were also able to determine the importance of the liver in conjugation of exogenous dopamine because this compound was given to both groups of patients. The concentrations of conjugated amines were within the normal range in the patients undergoing liver transplantation, and administered dopamine was conjugated to a similar extent in the two groups of patients. The data suggest that the liver is not indispensable for the conjugation of circulating catecholamines.


Multifaceted modes of γ-tubulin complex recruitment and microtubule nucleation at mitotic centrosomes.
Microtubule nucleation is mediated by γ-tubulin ring complexes (γ-TuRCs). In most eukaryotes, a GCP4/5/4/6 "core" complex promotes γ-tubulin small complex (γ-TuSC) association to generate cytosolic γ-TuRCs. Unlike γ-TuSCs, however, this core complex is non-essential in various species and absent from budding yeasts. In Drosophila, Spindle defective-2 (Spd-2) and Centrosomin (Cnn) redundantly recruit γ-tubulin complexes to mitotic centrosomes. Here, we show that Spd-2 recruits γ-TuRCs formed via the GCP4/5/4/6 core, but Cnn can recruit γ-TuSCs directly via its well-conserved CM1 domain, similar to its homologs in budding yeast. When centrosomes fail to recruit γ-tubulin complexes, they still nucleate microtubules via the TOG domain protein Mini-spindles (Msps), but these microtubules have different dynamic properties. Our data, therefore, help explain the dispensability of the GCP4/5/4/6 core and highlight the robustness of centrosomes as microtubule organizing centers. They also suggest that the dynamic properties of microtubules are influenced by how they are nucleated.


An update on the technique of double-contrast arthrotomography of the shoulder.
We review the technique of double-contrast arthrotomography (DCAT) including reference to a new, superficial and bevel-oriented puncture and the use of a special density compensation filter. We have found it possible to demonstrate the varieties, size and exact location of rotator cuff tears in the coronal and sagittal planes. Adaptation of the method to studies of the glenoid labrum also yields excellent results. DCAT is now the best technique of shoulder arthrography.


Blind loop perforation after side-to-side ileocolonic anastomosis.
Blind loop syndrome after side-to-side ileocolonic anastomosis is a well-recognized entity even though its incidence and complication rates are not clearly defined. The inevitable dilation of the ileal cul-de-sac leads to stasis and bacterial overgrowth which eventually leads to mucosal ulceration and even full-thickness perforation. Blind loop syndrome may be an underestimated complication in the setting of digestive surgery. It should always be taken into account in cases of acute abdomen in patients who previously underwent right hemicolectomy. We herein report 3 patients who were diagnosed with perforative blind loop syndrome a few years after standard right hemicolectomy followed by a side-to-side ileocolonic anastomosis.


Interferon consensus sequence binding protein (ICSBP) decreases beta-catenin activity in myeloid cells by repressing GAS2 transcription.
The interferon consensus sequence binding protein (ICSBP) is an interferon regulatory transcription factor, also referred to as IRF8. ICSBP acts as a suppressor of myeloid leukemia, although few target genes explaining this effect have been identified. In the current studies, we identified the gene encoding growth arrest specific 2 (GAS2) as an ICSBP target gene relevant to leukemia suppression. We find that ICSBP, Tel, and histone deacetylase 3 (HDAC3) bind to a cis element in the GAS2 promoter and repress transcription in myeloid progenitor cells. Gas2 inhibits calpain protease activity, and beta-catenin is a calpain substrate in these cells. Consistent with this, ICSBP decreases beta-catenin protein and activity in a Gas2- and calpain-dependent manner. Conversely, decreased ICSBP expression increases beta-catenin protein and activity by the same mechanism. This is of interest, because decreased ICSBP expression and increased beta-catenin activity are associated with poor prognosis and blast crisis in chronic myeloid leukemia (CML). We find that the expression of Bcr/abl (the CML oncoprotein) increases Gas2 expression in an ICSBP-dependent manner. This results in decreased calpain activity and a consequent increase in beta-catenin activity in Bcr/abl-positive (Bcr/abl(+)) cells. Therefore, these studies have identified a Gas2/calpain-dependent mechanism by which ICSBP influences beta-catenin activity in myeloid leukemia.


The role of phosphorylation in the interaction of rabbit muscle phosphofructokinase with F-actin.
The role of phosphorylation in the regulation of rabbit muscle phosphofructokinase was investigated by monitoring the effect of this covalent modification on the steady-state kinetics and complex formation between F-actin and the enzyme. Binding of phosphofructokinase to F-actin at pH 7.0 and 23 degrees C was monitored by sedimentation. These experiments show that phosphorylated phosphofructokinase has a higher apparent affinity for F-actin than does the dephosphorylated form. Control experiments showed that the complex formation is specific. Steady-state kinetic measurements at pH 7.0, 23 degrees C, showed that the presence of F-actin did not significantly affect the basic kinetic properties of the dephosphorylated form. Under identical conditions, F-actin acted as a positive effector of the phosphorylated form, and the effect of F-actin is specific. Results from these in vitro studies are consistent with in vivo observations which show that upon stimulation of muscle contraction, the enzyme is phosphorylated to a greater extent and the binding to the muscle matrix is increased. Hence, phosphorylation of phosphofructokinase does not only alter the kinetic behavior of the enzyme, but also serves as a means to regulate the compartmentalization of the enzyme in order to provide energy to the cellular component where it is needed.


Modulatory multiplicity in the functional repertoire of the feeding mechanism in cichlid fishes. I. Piscivores.
Among piscivorous cichlids consistent differences have been recorded between ambush and pursuit hunters with respect to electromyographic, kinematic, pressure and behavioral profiles during prey capture by high speed inertial suction. Piscivorous cichlids possess a repertoire of at least two patterns of prey capture, each of which is characterized by an extreme regularity of the kinematic, pressure, electromyographic and behavioral profiles. The nature and locomotory behavior of the prey, visually analyzed by the predator during the prestrike stalk, determine which of the two preprogrammed patterns is recruited. Agile and elusive prey invariably will elicit a preprogrammed motor output (stereotyped motor pattern) that produces the greatest suction velocities in both ambush and pursuit hunters. The greater the kinematic and suction velocities, the greater the overlap of the firing sequences of antagonistic muscle complexes. The opercular and branchiostegal apparati function as an exceedingly effective anti-backwash device, damping potential fluid oscillations within the oropharynx. Mastication occurs by triphasic movements and actions of muscles of the upper and lower pharyngeal jaws in both ambush and pursuit hunters. The lower pharyngeal jaw is acted upon by a force couple of which the fourth levator externus on one hand and the pharyngocleithralis externus and pharyngohyoideus on the other hand are the antagonistic components. Furthermore, the lower pharyngeal jaw is suspended by a muscular sling, the tension of which can be modified continuously. It is postulated that the switch from insectivorous to piscivorous feeding regimes (and perhaps vice versa) is accomplished by very minor structural and functional modifications, because the modulatory multiplicity and total range of repertories of the feeding machinery of the two trophic groups overlap significantly. Piscivorous cichlids may not have arisen by orthoselection in gradually-changing lineages, but represent the differential success of subsets from a random pool of speciation events. Adaptive features identified as characteristic for piscivory could have evolved in multiple and independent lineages at a punctuational mode and tempo.


N,N-Bis(trifluoromethylquinolin-4-yl)diamino alkanes: synthesis and antimalarial activity.
A series of N,N-bis(trifluoromethylquinolin-4-yl)- and N,N-bis[2,8-bis(trifluoromethyl)quinolin-4-yl] diamino alkane and piperazine derivatives were synthesised by employing a simple and rapid displacement reaction of the 4-chloro group on the 2-trifluoromethyl- and 2,8-bis(trifluoromethyl)-quinoline by diaminoalkane or piperazine groups. Results of in vitro antimalarial activity evaluations of these compounds against the chloroquine-sensitive (D10) and chloroquine-resistant (K1) strains of Plasmodium falciparum indicate that compounds with trifluoromethyl groups in both the 2 and 8 positions coupled with diaminoalkyl bridging chains of 2 to 6 carbon atoms exhibit a slightly higher activity than compound with only a trifluoromethyl group at position 2, and those with a piperazine bridge. These compounds exhibit higher activity in the chloroquine-resistant than in the chloroquine-sensitive strains of the Plasmodium. Comparative studies indicate that the compounds are more selective in their cytotoxicity against the parasite cells. Except for compounds containing a piperazine bridge, this new series of compounds interact with ferriprotoporphyrin IX to more or less the same extent.


Role of the hypocretin (orexin) receptor 2 (Hcrt-r2) in the regulation of hypocretin level and cataplexy.
Hypocretin receptor-2 (Hcrt-r2)-mutated dogs exhibit all the major symptoms of human narcolepsy and respond to drugs that increase or decrease cataplexy as do narcoleptic humans; yet, unlike narcoleptic humans, the narcoleptic dogs have normal hypocretin levels. We find that drugs that reduce or increase cataplexy in the narcoleptic dogs, greatly increase and decrease, respectively, hypocretin levels in normal dogs. The effects of these drugs on heart rate and blood pressure, which were considerable, were not correlated with their effects on cataplexy. Administration of these drugs to Hcrt-r2-mutated dogs produced indistinguishable changes in heart rate and blood pressure, indicating that neither central nor peripheral Hcrt-r2 is required for these cardiovascular effects. However, in contrast to the marked Hcrt level changes in the normal dogs, these drugs did not alter hypocretin levels in the Hcrt-r2 mutants. We conclude that Hcrt-r2 is a vital element in a feedback loop integrating Hcrt, acetylcholine, and norepinephrine function. In the absence of functional Hcrt-r2, Hcrt levels are not affected by monoaminergic and cholinergic drugs, despite the strong modulation of cataplexy by these drugs. Conversely, strong transient reductions of Hcrt level by these drugs do not produce episodes of cataplexy in normal dogs. The Hcrt-r2 mutation causes drug-induced cataplexy by virtue of its long-term effect on the functioning of other brain systems, rather than by increasing the magnitude of phasic changes in Hcrt level. A similar mechanism may be operative in spontaneous cataplexy in narcoleptic dogs as well as in narcoleptic humans.


New Formulations of Methylphenidate for the Treatment of Attention-Deficit/Hyperactivity Disorder: Pharmacokinetics, Efficacy, and Tolerability.
Psychostimulants are the recommended first-line pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD). Methylphenidate is one of the most commonly used psychostimulants worldwide. Given that immediate-release and/or tablet/capsule formulations may decrease adherence to methylphenidate treatment, several drug companies have been developing novel long-acting and/or liquid/chewable formulations that may improve adherence as well as (for long-acting formulations) reduce abuse potential, decrease stigma associated with multiple administrations per day, and decrease the potential for adverse effects related to dosage peak. Here, we review the pharmacokinetics, efficacy, and tolerability of novel formulations of methylphenidate that are in development or have been approved by the US FDA or European Medicines Agency (EMA) in the last 5 years. We searched the websites of the FDA, EMA, ClinicalTrials.gov, and the pertinent drug companies. We also searched PubMed, Ovid databases (MEDLINE, PsycINFO, Embase + Embase classic), and ISI Web of Knowledge (Web of Science [Science Citation Index Expanded], Biological Abstracts, Biosis, Food Science and Technology Abstracts) to retrieve any additional pertinent information. We found data from trials for the following compounds: (1) methylphenidate extended-release oral suspension (MEROS; NWP06, Quillivant™); (2) methylphenidate extended-release chewable capsules (NWP09, QuilliChew ER™); (3) methylphenidate hydrochloride extended-release capsules (Aptensio XR™); (4) methylphenidate extended-release orally disintegrating tablets (XR-ODT; NT-0102, Cotempla™); (5) ORADUR technology (once-daily tamper-resistant formulation) methylphenidate sustained release (SR); and (6) methylphenidate modified-release (HLD-200; Bejorna™). Overall, available evidence based on trials suggests these compounds have good efficacy and tolerability. Future research should further explore the effectiveness and tolerability of these new formulations as well as their potential to improve adherence to treatment in the 'real world' via pragmatic trials.


Amoxicillin-bearing microparticles: potential in the treatment of Listeria monocytogenes infection in Swiss albino mice.
The present study was aimed at evaluating the effectiveness of amoxicillin-bearing HSA (human serum albumin) and PLGA [poly(lactic-co-glycolic acid)] microparticles in combating Listeria monocytogenes infection in Swiss albino mice. Amoxicillin-bearing HSA microspheres were prepared by chemical cross-linking of a drug/albumin mixture with glutaraldehyde, and PLGA microspheres were prepared by the W/O/W (water-in-oil-in-water) emulsion technique. The microspheres were characterized for their size, ζ potential and entrapment efficiency using SEM (scanning electron microscopy) and a Zetasizer. Release kinetics was performed in a phosphate buffer (pH 7.4) at 37°C simulating physiological conditions. Bacterial burden in various vital organs and survival data established enhanced efficacy of PLGA and HSA microspheres as compared with free drug. Among the two delivery systems, PLGA microspheres, when compared with HSA microspheres, imparted better efficacy in terms of reduction in bacterial load as well as increase in survival. The results of the present study clearly demonstrate that microparticles successfully target the infected macrophages and the approach could be well exploited for targeting the intracellular pathogens as well.


Surgeon-performed ultrasound for the assessment of abdominal injuries.
The use of ultrasound for the investigation of urgent diagnostic dilemmas is by no means new. Although it has been widely used for almost 40 years, during the past two decades ultrasound has achieved a primary role in the investigation of emergent conditions, notably in the trauma setting. This is further underscored by the American College of Surgeons (ACS) training initiatives. In addition to the basic ultrasound course sponsored by the ACS at the Clinical Congress meetings, the ACS will offer a specialty module course, "Ultrasound in the Acute Setting," that covers ultrasound as used in trauma, critical care, and acute general surgical problems. This initiative underscores the surgeons' interest in having ultrasound as an integral part of their trauma practice. Having the ability to perform and interpret the ultrasound examination gives the surgeon the advantage of obtaining immediate information about the patient. Considering the pace of the trauma setting, ultrasound is an ideal modality for assessment of these patients. It should be the initial diagnostic test for the evaluation of patients with precordial wounds and blunt truncal injuries because it is rapid and accurate, and it augments the surgeon's diagnostic capabilities.


Validation of the WHOQOL-Bref instrument in Brazilian sign language (Libras).
The recognition of the Brazilian Sign Language (Libras) as the official language of the Brazilian deaf, in 2002, reaffirms the linguistic and cultural particularities of the deaf population. Therefore, there is a lack of a validated instrument for assessing the Quality of Life of deaf people using Libras. With authorization from the World Health Organization (WHO), a version of the WHOQOL-Bref in Libras was developed, called WHOQOL-Bref/Libras. However, its psychometric properties have not been examined as yet. Therefore, the purpose of this work is to perform the psychometric validation of the WHOQOL-Bref/Libras. WHOQOL-Bref/Libras and a sociodemographic questionnaire were applied to 311 deaf people from the five Brazilian regions. To assess temporal stability, the questionnaire was readministered to 52 deaf people, over an interval of 2 weeks. WHOQOL-Bref/Libras demonstrated satisfactory psychometric values for reliability, discriminant and construct validity, temporal stability, and internal consistency. Cronbach's alpha coefficient showed satisfactory values for each of the WHOQOL-Bref domains: Physical health (0.641), Psychological (0.705), Environment (0.710), and Overall-Bref domains (0.873). The WHOQOL-Bref/Libras is the appropriate option to assess the quality of life of deaf people who communicate through Libras. WHOQOL-Bref/Libras had a satisfactory psychometric performance; therefore, it is a valid option that will provide autonomous participation for the deaf in quality of life investigations.


Asbestos fibres in bronchoalveolar lavage fluid from asbestos workers: examination by electron microscopy.
The uncoated and coated fibre load in bronchoalveolar lavage (BAL) fluid was assessed using light microscopy, scanning electron microscopy, and x ray microanalysis in 15 subjects with previous, unprotected exposure to asbestos, including three with clinical and radiological evidence of asbestosis, and in 13 urban dwelling control subjects with no known occupational exposure to asbestos. The mean ferruginous body count per ml BAL fluid in asbestos exposed subjects as determined by light microscopy was 52 (range 0-333). No ferruginous bodies were detected in control subjects. The mean fibre count per ml BAL fluid in asbestos exposed subjects as determined by electron microscopy was 793 (133-3700), significantly greater than 239 (44-544) in controls (p less than 0.05). Electron microscopic counts correlated with duration of previous exposure to asbestos (r = 0.47, p less than 0.05) and with percentage neutrophil counts (r = 0.53, p less than 0.025). There was no relation between electron microscopic fibre counts and light microscopic ferruginous body counts. In 11 asbestos exposed cases x ray microanalysis confirmed the presence of asbestos and in six the asbestos fibre type was clearly identified. Of five subjects showing no asbestos bodies by light microscopy, all showed fibres by electron microscopy, and in three cases the presence of asbestos was confirmed by microanalysis. Among control subjects, fibres were either large organic fibres or smaller particles which microanalysis showed were not asbestos. In only one control case were a few fibres identified which were confirmed as asbestos fibres on microanalysis. Electron microscopic examination of BAL fluid may confirm past exposure to asbestos and probably gives a crude quantitative estimate of asbestos load.


Serotonin function is associated with behavioral response to a novel conspecific in marmosets.
The function of the central nervous system neurotransmitter serotonin (5-HT) contributes to individual differences in impulsive behavior in humans and nonhuman primates. We investigated the relationship between 5-HT function and behavioral responses to a novel social scenario in marmosets. In the first study, marmosets (n=10) were treated orally with fluoxetine HCl (FLX) or vehicle for two trial periods and exposed to a novel conspecific for a 20-min trial following each treatment. Levels of behavioral inhibition in response to a novel conspecific were quantified. The animals exhibited less inhibition toward the novel conspecific following the 14-day FLX treatment than they did following the vehicle treatment. In the second study we first characterized the parameters of the marmoset peripheral 5-HT system and further assessed the relationship between natural variation in peripheral 5-HT and 5-HIAA levels with behavioral inhibition in response to a novel conspecific (n=14). Individual peripheral 5-HT and 5-HIAA levels were higher in animals that exhibited more inhibition in response toward the stranger. We conclude that serotonergic influences play a role in behavioral response to a novel conspecific in marmosets.


Cargo delivery to adhering myoblast cells from liposome-containing poly(dopamine) composite coatings.
Designing surfaces to deliver therapeutic compounds to adhering cells is of paramount importance for both implantable devices and tissue engineering. We report the assembly of composite films consisting of liposomes as drug deposits in a poly(dopamine) matrix. We monitor the film assembly using a quartz crystal microbalance with dissipation. We assess the response of adhering myoblast cells to these films containing fluorescent lipids in terms of uptake efficiency and cell mean fluorescence using flow cytometry. The viability of adhering myoblast cells, when the hydrophobic cytotoxic compound thiocoraline is entrapped in the lipid membrane, is assessed for different films. Coatings with one or two liposome deposition steps are considered. Further, the effect of the polymer separation layers between the liposome layers is determined. We found that it is possible to use the different nano-engineered composite coatings to impose a corresponding cellular response, e.g., a higher amount of embedded liposomes leads to higher uptake efficiency of the fluorescent lipids and cell mean fluorescence or a higher reduction in the viability of the adhering cells. Assessment of the uptake efficiency and cell mean fluorescence over time reveals a decrease in both parameters over 48 h. Our results demonstrate the ability to affect the cell response depending on the properties of the films, opening up a variety of opportunities for biomedical applications in substrate-mediated drug delivery.


Recent developments in nanomedicine for melanoma treatment.
Melanoma is a most aggressive skin cancer with limited therapeutic options and its incidence is increasing rapidly in recent years. The discovery and application of new targeted therapy agents have shown significant benefits. However, adverse side-effects and resistance to chemotherapy remain formidable challenges in the clinical treatment of malignant melanoma. Nanotherapeutics offers an important prospect of overcoming these drawbacks. The anti-tumoral applications of nanomedicine are varied, including those in chemotherapy, RNA interference, photothermal therapy, and photodynamic therapy. Furthermore, nanomedicine allows delivery of the effector structures into the tumor site via passive or active targeting, thereby allowing increased therapeutic specificity and reduced side effects. In this review, we summarize the latest developments in the application of nanocarrier-mediated targeted drug delivery to melanoma and nanomedicine-related clinical trials in melanoma treatment. We also discuss existing problems and opportunities for future developments, providing direction and new thoughts for further studies.


Evaluation of mineral oil saturated hydrocarbons (MOSH) and mineral oil aromatic hydrocarbons (MOAH) in pure mineral hydrocarbon-based cosmetics and cosmetic raw materials using 1H NMR spectroscopy.
Mineral hydrocarbons consist of two fractions, mineral oil saturated hydrocarbons (MOSH) and mineral oil aromatic hydrocarbons (MOAH). MOAH is a potential public health hazard because it may include carcinogenic polycyclic compounds. In the present study, 400 MHz nuclear magnetic resonance (NMR) spectroscopy was introduced, in the context of official controls, to measure MOSH and MOAH in raw materials or pure mineral hydrocarbon final products (cosmetics and medicinal products). Quantitative determination (qNMR) has been established using the ERETIC methodology (electronic reference to access in vivo concentrations) based on the PULCON principle (pulse length based concentration determination). Various mineral hydrocarbons (e.g., white oils, paraffins or petroleum jelly) were dissolved in deuterated chloroform. The ERETIC factor was established using a quantification reference sample containing ethylbenzene and tetrachloronitrobenzene. The following spectral regions were integrated: MOSH δ 3.0 - 0.2 ppm and MOAH δ 9.2 - 6.5, excluding solvent signals. Validation showed a sufficient precision of the method with a coefficient of variation <6% and a limit of detection <0.1 g/100 g. The applicability of the method was proven by analysing 27 authentic samples with MOSH and MOAH contents in the range of 90-109 g/100 g and 0.02-1.10 g/100 g, respectively. It is important to distinguish this new NMR-approach from the hyphenated liquid chromatography-gas chromatography methodology previously used to characterize MOSH/MOAH amounts in cosmetic products. For mineral hydrocarbon raw materials or pure mineral hydrocarbon-based cosmetic products, NMR delivers higher specificity without any sample preparation besides dilution. Our sample survey shows that previous methods may have overestimated the MOAH amount in mineral oil products and opens new paths to characterize this fraction. Therefore, the developed method can be applied for routine monitoring of consumer products aiming to minimize public health risks.