Payment methods for outpatient care facilities.
Outpatient care facilities provide a variety of basic healthcare services to individuals who do not require hospitalisation or institutionalisation, and are usually the patient's first contact. The provision of outpatient care contributes to immediate and large gains in health status, and a large portion of total health expenditure goes to outpatient healthcare services. Payment method is one of the most important incentive methods applied by purchasers to guide the performance of outpatient care providers. To assess the impact of different payment methods on the performance of outpatient care facilities and to analyse the differences in impact of payment methods in different settings. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), 2016, Issue 3, part of the Cochrane Library (searched 8 March 2016); MEDLINE, OvidSP (searched 8 March 2016); Embase, OvidSP (searched 24 April 2014); PubMed (NCBI) (searched 8 March 2016); Dissertations and Theses Database, ProQuest (searched 8 March 2016); Conference Proceedings Citation Index (ISI Web of Science) (searched 8 March 2016); IDEAS (searched 8 March 2016); EconLit, ProQuest (searched 8 March 2016); POPLINE, K4Health (searched 8 March 2016); China National Knowledge Infrastructure (searched 8 March 2016); Chinese Medicine Premier (searched 8 March 2016); OpenGrey (searched 8 March 2016); ClinicalTrials.gov, US National Institutes of Health (NIH) (searched 8 March 2016); World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (searched 8 March 2016); and the website of the World Bank (searched 8 March 2016).In addition, we searched the reference lists of included studies and carried out a citation search for the included studies via ISI Web of Science to find other potentially relevant studies. We also contacted authors of the main included studies regarding any further published or unpublished work. Randomised trials, non-randomised trials, controlled before-after studies, interrupted time series, and repeated measures studies that compared different payment methods for outpatient health facilities. We defined outpatient care facilities in this review as facilities that provide health services to individuals who do not require hospitalisation or institutionalisation. We only included methods used to transfer funds from the purchaser of healthcare services to health facilities (including groups of individual professionals). These include global budgets, line-item budgets, capitation, fee-for-service (fixed and unconstrained), pay for performance, and mixed payment. The primary outcomes were service provision outcomes, patient outcomes, healthcare provider outcomes, costs for providers, and any adverse effects. At least two review authors independently extracted data and assessed the risk of bias. We conducted a structured synthesis. We first categorised the comparisons and outcomes and then described the effects of different types of payment methods on different categories of outcomes. We used a fixed-effect model for meta-analysis within a study if a study included more than one indicator in the same category of outcomes. We used a random-effects model for meta-analysis across studies. If the data for meta-analysis were not available in some studies, we calculated the median and interquartile range. We reported the risk ratio (RR) for dichotomous outcomes and the relative change for continuous outcomes. We included 21 studies from Afghanistan, Burundi, China, Democratic Republic of Congo, Rwanda, Tanzania, the United Kingdom, and the United States of health facilities providing primary health care and mental health care. There were three kinds of payment comparisons. 1) Pay for performance (P4P) combined with some existing payment method (capitation or different kinds of input-based payment) compared to the existing payment methodWe included 18 studies in this comparison, however we did not include five studies in the effects analysis due to high risk of bias. From the 13 studies, we found that the extra P4P incentives probably slightly improved the health professionals' use of some tests and treatments (adjusted RR median = 1.095, range 1.01 to 1.17; moderate-certainty evidence), and probably led to little or no difference in adherence to quality assurance criteria (adjusted percentage change median = -1.345%, range -8.49% to 5.8%; moderate-certainty evidence). We also found that P4P incentives may have led to little or no difference in patients' utilisation of health services (adjusted RR median = 1.01, range 0.96 to 1.15; low-certainty evidence) and may have led to little or no difference in the control of blood pressure or cholesterol (adjusted RR = 1.01, range 0.98 to 1.04; low-certainty evidence). 2) Capitation combined with P4P compared to fee-for-service (FFS)One study found that compared with FFS, a capitated budget combined with payment based on providers' performance on antibiotic prescriptions and patient satisfaction probably slightly reduced antibiotic prescriptions in primary health facilities (adjusted RR 0.84, 95% confidence interval 0.74 to 0.96; moderate-certainty evidence). 3) Capitation compared to FFSTwo studies compared capitation to FFS in mental health centres in the United States. Based on these studies, the effects of capitation compared to FFS on the utilisation and costs of services were uncertain (very low-certainty evidence). Our review found that if policymakers intend to apply P4P incentives to pay health facilities providing outpatient services, this intervention will probably lead to a slight improvement in health professionals' use of tests or treatments, particularly for chronic diseases. However, it may lead to little or no improvement in patients' utilisation of health services or health outcomes. When considering using P4P to improve the performance of health facilities, policymakers should carefully consider each component of their P4P design, including the choice of performance measures, the performance target, payment frequency, if there will be additional funding, whether the payment level is sufficient to change the behaviours of health providers, and whether the payment to facilities will be allocated to individual professionals. Unfortunately, the studies included in this review did not help to inform those considerations.Well-designed comparisons of different payment methods for outpatient health facilities in low- and middle-income countries and studies directly comparing different designs (e.g. different payment levels) of the same payment method (e.g. P4P or FFS) are needed.


Chemical phenotypes of the hmg1 and hmg2 mutants of Arabidopsis demonstrate the in-planta role of HMG-CoA reductase in triterpene biosynthesis.
Plants produce a wide variety of cyclic triterpenes, such as sterols and triterpenoids, which are the major products of the mevalonate (MVA) pathway. It is important to understand the physiological functions of HMG-CoA reductase (HMGR) because HMGR is the rate-limiting enzyme in the MVA pathway. We have previously isolated Arabidopsis mutants in HMG1 and HMG2. Although the biochemical function of HMGR2 has been thought to be almost equal to that of HMGR1, based on similarities in their sequences, the phenotypes of mutants in these genes are quite different. Whereas hmg2 shows no abnormal phenotype under normal growth conditions, hmg1 shows pleiotropic phenotypes, including dwarfing, early senescence, and male sterility. We previously postulated that the 50% decrease in the sterol content of hmg1, as compared to that in the wild type, was a cause of these phenotypes, but comprehensive triterpene profiles of these mutants had not yet been determined. Here, we present the triterpene profiles of hmg1 and hmg2. In contrast to hmg1, hmg2 showed a sterol content 15% lower than that of the wild type. A precise triterpenoid quantification using synthesized deuterated compounds of beta-amyrin (1), alpha-amyrin (2), and lupeol (3) showed that the levels of triterpenoids in hmg1 and hmg2 were 65% and 25% lower than in the wild type (WT), respectively. These results demonstrate that HMGR2 as well as HMGR1 is responsible for the biosynthesis of triterpenes in spite of the lack of visible phenotypes in hmg2.


[Phonosurgical methods of treatment in unilateral vocal folds paralysis].
Glottal insufficiency (GI) is a cause of breathy voice that can profoundly affect quality of voice. Main causes are unilateral vocal fold paralysis or endoscopic cordectomy for the early treatment of laryngeal cancer of the glottis. The main strategy in surgical treatment is type I medialization thyroplasty according to Isshiki with the use of implants e.g. silastic, hydroxyapatite, titanium, Gore-Tex or Montgomery. Other procedures are arytenoid adduction, the injection laryngoplasty via thyrohyoid and cricothyroid approach and laryngeal reinnervation. To predict successful voice outcome and to prevent revision surgery, surgeon must choose appropriate size of the implant on the basis of subjective intraoperative visualization of the glottal closure during phonation in fibroptic laryngoscopy and by objective measurement of peroperative maximal phonation time (MPT) or direct peak subglottic pressure (DPSP) through a catheter inserted into the cricothyroid membrane. Majority of otolaryngologist recommend surgical treatment 12 months after the onset of unilateral vocal fold paralysis, before performing any permanent intervention, because some patients will have full or partial recovery of the recurrent laryngeal nerve (RLN) function and others will have adequate compensation from the intact side.


[Study on stability of beta-cyclodextrin to chlorogenic acid].
To investigate the stabilizing effect of chlorogenic acid against beta-cyclodextrin, beta-cyclodextrin inclusion compound of chlorogenic acid was prepared by liquid phase method, and affirmed by UV and different thermal analysis. Stability in solution was contrasted between chlorogenic acid and its inclusion complex with beta-cyclodextrin, and the stability of the latter was increased.


Biochemistry of the augmenting-reducing response in visual evoked potentials.
The augmenting-reducing response in visual evoked potentials (VEP) has between shown to be a useful tool in psychiatric research. A series of studies has been devoted to the search for the biochemical basis of this phenomenon. An augmenter response in VEP is shown to be clearly related to low levels of endorphins, 5-HIAA and homovanillic acid in CSF and to low serum-dopamine-beta-hydroxylase activity, while no significant relationship was found with 4-hydroxy-3-methoxyphenylethylene glycol or tryptophan in CSF or MAO in thrombocytes. The results indicate that an augmenter response in VEP is related to low activity in the serotoninergic, dopaminergic and endophinergic pathways in CNS.


[Observation of the clinical effects on perimenopausal syndrome treated with the transcutaneous electrostimulation at Shuitu (ST 10) and the seed-pressure therapy at the auricular points].
To compare the differences in the clinical therapeutic effects on perimenopausal syndrome (PMS) between the combined treatment with the transcutaneous electrostimulation at Shuitu (ST 10) and the seed-pressure therapy at the auricular points and the hormone replacement therapy. A total of 64 PMS patients were divided into an observation group (30 cases) and a control group (34 cases) according to patient's willingness. In the observation group, the transcutaneous electrostimulation at Shuitu (ST 10) was combined with the seed-pressure therapy at the auricular points. The stimulation intensity at Shuitu (ST 10) was ranged from 15 to 20 mA, for 20 min in each treatment, twice a week. The 8 treatments made one course and 3 courses were required. Additionally, the seed-pressure therapy was used at neifenmi (CO18), Shenmen (TF4), luanchao, zigong, gan (CO12), shen (CO10), once a week, retained for 5 days. The 4-week treatment was as one course and a total of 3 courses were required. In the control group, the hormone replacement therapy was applied. On Day 5 of menstruation, progynova was prescribed for oral administration, 1 mg, once a day, continuously for 21 days. On Day 12 in the oral administration of progynova, dydrogesterone was used, 20 mg, once every day, continuously for 10 days. Totally, 3 courses were required. Separately, before treatment and in 1 and 3 months after treatment, Kuppermann score, the sexual hormone levels [follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2)] and the adverse reactions were observed in the patients of the two groups. In 1 and 3 months after treatment, Kuppermann scores were reduced significantly as compared with those before treatment in the two groups (all P<0.05). The levels of serum FSH and LH were reduced remarkably as compared with those before treatment in the two groups (all P<0.05) and the level of serum E2 was increased remarkably as compared with that before treatment in the two groups (all P<0.05). After treatment, the differences in the above indexes were not significant between the two groups (all P>0.05). In the control group, the incidences of the adverse reactions such as vaginal bleeding, bread distending pain and endometrial thickening were higher than those in the observation group [17.6% (6/34) vs 0% (0/30), 20.6% (7/34) vs 3.3% (1/30), 8.8% (3/34) vs 0% (0/30), all P<0.05]. The combined treatment with the transcutaneous electrostimulation at Shuitu (ST 10) and the seed-pressure therapy at the auricular points achieves the similar therapeutic effects on PMS as compared with the hormone replacement therapy. This combined therapy effectively relieves the clinical symptoms and improves the sexual hormone levels. The adverse reactions and the complications are less obviously as compared with the hormone replacement therapy.


Refining the picture: new records to the lichen biota of Italy.
Based on the analysis of both historical and recent collections, this paper reports an annotated list of taxa which are new to the lichen biota of Italy or of its administrative regions. Specimens were identified using a dissecting and a compound microscope; routine chemical spot tests and standardized thin-layer chromatography (TLC or HPTLC). The list includes 225 records of 153 taxa. Twenty taxa are new to Italy, the others are new to one or more administrative regions, with 15 second records and 5 third records for Italy. Some of the species belong to recently-described taxa, others are poorly known, sterile or ephemeral lichens which were largely overlooked in Italy. Several species are actually rare, either because of the rarity of their habitats (e.g. old-growth forests), or because in Italy they are at the margins of their bioclimatic distribution. The picture of the lichen biota of Italy has now new pixels, but its grain is still coarse. Further analysis of historical collections, increased efforts in the exploration of some areas, and the taxonomic revision of critical groups are still necessary to provide more complete distributional data for new biogeographic hypotheses, taxonomic and ecological research, and biodiversity conservation.


Burden and Coping Strategies of Hypoglycemia in People with Diabetes.
Hypoglycemia is a limiting adverse effect of glucose-lowering medications and particularly insulin replacement therapy. This review provides insights into the burden of hypoglycemia in the management of diabetes and outlines strategies available to reduce the risk of hypoglycemia and improve patients' well-being. People with type 1 diabetes are primarily affected by hypoglycemic episodes which are associated with direct physical harms like injuries and cardiac events as well as indirect psychosocial consequences including constant anxiety, absenteeism, increased healthcare costs and overall poorer quality of life. These complications are more prominent amongst individuals with hypoglycemia unawareness or overnight hypoglycemia and could even extend to caregivers such as parents of children with diabetes. Patients experiencing frequent or severe hypoglycemic events might also develop a pathological fear of hypoglycemia and adopt aberrant behaviors intending to maintain higher blood glucose levels. Modern pharmaceutical options with a safer profile in terms of hypoglycemia are available including novel basal insulins with lower rates of nocturnal hypoglycemia along with ultra-rapid-acting insulin analogs with a shorter duration of action that might avert late post-meal hypoglycemia. Continuous glucose monitoring and sensor-augmented insulin pump therapy with low glucose suspend technology can also prevent hypoglycemia, although concerns about cost and patient satisfaction remain. Advancements in insulin therapy and technological modalities should be coupled with ongoing education and support for patients to become co-managers of their disease and reduce the risk of hypoglycemia.


Oxygenation of Organoboronic Acids by a Nonheme Iron(II) Complex: Mimicking Boronic Acid Monooxygenase Activity.
Phenolic compounds are important intermediates in the bacterial biodegradation of aromatic compounds in the soil. An Arthrobacter sp. strain has been shown to exhibit boronic acid monooxygenase activity through the conversion of different substituted phenylboronic acids to the corresponding phenols using dioxygen. While a number of methods have been reported to cleave the C-B bonds of organoboronic acids, there is no report on biomimetic iron complex exhibiting this activity using dioxygen as the oxidant. In that direction, we have investigated the reactivity of a nucleophilic iron-oxygen oxidant, generated upon oxidative decarboxylation of an iron(II)-benzilate complex [(Tp(Ph2))Fe(II)(benzilate)] (Tp(Ph2) = hydrotris(3,5-diphenyl-pyrazol-1-yl)borate), toward organoboronic acids. The oxidant converts different aryl/alkylboronic acids to the corresponding oxygenated products with the incorporation of one oxygen atom from dioxygen. This method represents an efficient protocol for the oxygenation of boronic acids with dioxygen as the terminal oxidant.


Regulation of Drug Release by Tuning Surface Textures of Biodegradable Polymer Microparticles.
Generally, size, uniformity, shape, and surface chemistry of biodegradable polymer particles will significantly affect the drug-release behavior in vitro and in vivo. In this study, uniform poly(d,l-lactic-co-glycolide) (PLGA) and PLGA-b-poly(ethylene glycol) (PLGA-b-PEG) microparticles with tunable surface textures were generated by combining the interfacial instabilities of emulsion droplet and polymer-blending strategy. Monodisperse emulsion droplets containing polymers were generated through the microfluidic flow-focusing technique. The removal of organic solvent from the droplets triggered the interfacial instabilities (spontaneous increase in interfacial area), leading to the formation of uniform polymer particles with textured surfaces. With the introduction of homopolymer PLGA to PLGA-b-PEG, the hydrophobicity of the polymer system was tailored, and a qualitatively different interfacial behavior of the emulsion droplets during solvent removal was observed. Uniform polymer particles with tunable surface roughness were thus generated by changing the ratio of PLGA-b-PEG in the polymer blends. More interestingly, surface textures of the particles determined the drug-loading efficiency and release kinetics of the encapsulated hydrophobic paclitaxel, which followed a diffusion-directed drug-release pattern. The polymer particles with different surface textures demonstrated good cell viability and biocompatibility, indicating the promising role of the particles in the fields of drug or gene delivery for tumor therapy, vaccines, biodiagnostics, and bioimaging.


Effect of DHEA therapy on sexual behavior in female rats.
Delta-5 androgen therapies seem to enhance the sexual response in experimental animal models and in clinical trial. This study analyzed the influence of dehydroepiandrosterone (DHEA) administration on receptive and proceptive components of female rat sexual behavior. Ovariectomized (OVX) adult rats were divided in six groups submitted to the following treatments for 4 weeks: DHEA 0.5 and 5 mg/kg, by oral gavage, alone or in combination with estradiol benzoate 3 µg/rat; EB 3 and 10 µg/rat as control groups. All animals received progesterone (500 µg/rat) 4 h before the behavioral tests. All animals were tested for the following: receptivity and proceptivity weekly for 4 weeks; partner preference and paced mating behavior at the end of the treatments. Oral administration of DHEA at 5 mg/kg in EB primed rats was able to significantly increase proceptive behaviors, already after 1 week of treatment. The increase was more marked after 3 and 4 weeks of treatment. Behavioral changes were associated to modifications of circulating and brain level of allopregnanolone and beta-endorphin, although circulating hormonal levels were within a physiological range. Hormonal treatment using physiological doses of delta-5 androgens (DHEA) positively affects sexual motivation in OVX rats.


Isolation and characterization of IS1416 from Pseudomonas glumae, a new member of the IS3 family.
Isolation and characterization of four different insertion sequence (IS) elements from Pseudomonas glumae MAFF 302744 through transposition into the entrapment vector pSHI1063 are described. One of the elements, IS1416, was further characterized. IS1416 is 1322 bp long and carries 29-bp terminal inverted repeats flanked by a 3-bp direct duplication. IS1416 contains three open reading frames (ORFs), which are designated ORFA1, ORFA2, and ORFB, on one strand. Both DNA sequence of IS1416 and the deduced amino acid sequences of its ORFs strongly suggest that IS1416 is a member of the IS3 family, and is closely related to IS401 from Pseudomonas cepacia and IS51 from Pseudomonas syringae. To our knowledge, IS1416 is the first IS element isolated from P. glumae. The gene organization and possible regulation of transposition functions of IS1416 are also discussed.


Gene therapy, cell transplantation and stroke.
The use of neuroteratocarcinoma cells for transplantation therapy in stroke has emerged as a strategy for cell replacement therapy that has begun its transition from basic science laboratories to a clinical setting. Procurement logistics and novel neuroprotective functions associated with these cells allow neuroteratocarcinoma cells to serve as efficacious alternatives to using fetal cells as donor cell grafts for stroke therapy, although the optimal transplantation regimen must still be determined. In particular, the limitations of current stroke treatments and management reveal an urgent need to examine the efficacy of experimental treatments, such as neural transplantation, in order to develop better treatment therapies. This chapter will discuss the characteristics of NT2N cells, the role of the host brain microenvironment and NT2N cell grafts, laboratory research and clinical trials for the intracerebral transplantation of NT2N cells in stroke, the mechanisms underlying the grafts' effects, and NT2N cell grafts and the need for immunosuppression. This chapter will also highlight some of the most recent findings regarding NT2N cells.


Melodic Universals Emerge or Are Sustained Through Cultural Evolution.
To understand why music is structured the way it is, we need an explanation that accounts for both the universality and variability found in musical traditions. Here we test whether statistical universals that have been identified for melodic structures in music can emerge as a result of cultural adaptation to human biases through iterated learning. We use data from an experiment in which artificial whistled systems, where sounds produced with a slide whistle were learned by human participants and transmitted multiple times from person to person. These sets of whistled signals needed to be memorised and recalled and the reproductions of one participant were used as the input set for the next. We tested for the emergence of seven different melodic features, such as discrete pitches, motivic patterns, or phrase repetition, and found some evidence for the presence of most of these statistical universals. We interpret this as promising evidence that, similarly to rhythmic universals, iterated learning experiments can also unearth melodic statistical universals. More, ideally cross-cultural, experiments are nonetheless needed. Simulating the cultural transmission of artificial proto-musical systems can help unravel the origins of universal tendencies in musical structures.


The Aravind Pseudoexfoliation Study: 5-Year Postoperative Results. The Effect of Intraocular Lens Choice and Capsular Tension Rings.
We compared rates of intraocular lens (IOL) decentration, neodymium-doped yttrium aluminum garnet capsulotomy for posterior capsule opacification (PCO), and visual acuity (VA) in eyes with and without pseudoexfoliation (PEX) 5 years after undergoing cataract surgery. Prospective comparative interventional study. This multicenter study population included 1 eye of both 930 cataract patients with and 470 cataract patients without uncomplicated PEX (no small pupils or phacodonesis) all undergoing phacoemulsification by experienced Aravind Eye Care System surgeons. Eyes were randomized to either 1- or 3-piece intraocular lenses (IOLs). PEX eyes were also randomized to either receive or not receive a capsule tension ring. The main outcome measures included IOL decentration and PCO. Secondary outcomes included postoperative best-corrected VA. Follow-up was 86.2% in the PEX group and 86.7% in the control group at 5 years. The PEX group was older (P < .001) and had more men (P = .01). IOL decentration at 5 years was equally prevalent in PEX and control eyes (1.0% vs 1.1%, respectively, P = .8). Neodymium-doped yttrium aluminum garnet posterior capsulotomy rates for PCO were similar in the PEX group when compared with control subejcts (5.3% compared with 3.2%, respectively, P = .07). Best corrected VA was better at baseline and years 2 and 3 in the control group (P = .0001, P = .0005, and P = .02); however, there was no difference in BCVA at years 1, 4, and 5 between the PEX and control groups (P = .09, P = .29, and P = .5). In a large-scale, long-term, prospective comparative study of cataract surgery in eyes with uncomplicated PEX, the risks of IOL decentration and PCO were low and comparable to that in control subjects. When approaching cataract surgery in eyes with relatively uncomplicated PEX, neither IOL choice (1- vs 3-piece acrylic IOL) nor the presence/absence of a capsule tension ring affects outcomes at 5 years.


Self-Assembled Bifunctional Copper Hydroxide/Gold-Ordered Nanoarray Composites for Fast, Sensitive, and Recyclable SERS Detection of Hazardous Benzene Vapors.
Volatile organic compounds (VOCs), particularly monoaromatic hydrocarbon compounds (MACHs), pose a potential risk to the atmospheric environment and human health. Therefore, the progressive development of efficient detection methodologies is a pertinent need, which is still a challenge at present. In this study, we present a rapid and sensitive method to detect trace amounts of MACHs using a bifunctional SERS composite substrate. We prepared an Au/SiO2 enhanced layer and a porous Cu(OH)2 adsorption layer via microfluidic-assisted gas-liquid interface self-assembly. The composite substrate effectively monitored changes in benzaldehyde using time-varying SERS spectra, and track-specifically identified various VOCs such as benzene, xylene, styrene, and nitrobenzene. In general, the substrate exhibited a rapid response time of 20 s to gaseous benzaldehyde, with a minimum detection concentration of less than 500 ppt. Further experimental assessments revealed an optimum Cu(OH)2 thickness of the surrounding adsorption layer of 150 nm, which can achieve an efficient SERS response to MACHs. Furthermore, the recoverable and reusable property of the composite substrate highlights its practicality. This study presents a straightforward and efficient approach for detecting trace gaseous VOCs using SERS, with significant implications in the designing of SERS substrates for detecting other VOCs.


The symptomatic treatment of multiple system atrophy.
Multiple system atrophy (MSA) is a neurodegenerative disease of undetermined aetiology that occurs sporadically and manifests itself as a combination of parkinsonian, autonomic, cerebellar and pyramidal signs. Despite the lack of any effective therapy to reverse this condition, some of the symptoms may be, at least temporarily, improved with adequate symptomatic therapies. Medical treatment is largely aimed at mitigating the parkinsonian and autonomic features. The therapeutic results of levodopa therapy in cases of MSA are difficult to interpret because of their variability. Nevertheless, the statement that patients with MSA are non or poorly levodopa-responsive is misleading. Clinical and pathologically proven series document about 40-60% levodopa efficacy in patients with MSA presenting with predominant parkinsonian features. Unfortunately, other antiparkinsonian compounds (dopamine agonists, amantadine) are not more effective than levodopa. Orthostatic hypotension (OH) can be suspected from the patient's history and subsequently documented in the clinic by measuring lying and standing blood pressure. The diagnosis ideally should be confirmed in the laboratory with additional tests to determine the cause and evaluate the functional deficit, so as to aid treatment. A variety of pharmacological agents with different mechanisms of action have been used in MSA to reduce OH when this is symptomatic. OH can also be alleviated by avoiding aggravating factors, such as the effects of food, micturition, exposure to a warm environment and physiological diurnal changes and by using other non-pharmacological strategies. The treatment of the very common genito-urinary symptoms (incontinence, retention, impotence) should also be considered in order to improve the quality of life of these patients.


Sjögren's syndrome and primary biliary cirrhosis: presence of autoantibodies to purified mitochondrial 2-OXO acid dehydrogenases.
Sjögren's syndrome is well known for the presence of antibodies directed at specific nuclear antigens. However, the presence of antibodies reacting with a variety of other self antigens, including antimitochondrial antibodies, has often been reported although their significance is unknown. Moreover, patients with Sjögren's syndrome have been occasionally reported to be concordant with primary biliary cirrhosis. To address this issue we studied in a group of 96 patients with Sjögren's syndrome the presence of autoantibodies to the dihydrolipoamide acetyltransferases of both pyruvate dehydrogenase and branch chain ketoacid dehydrogenase and to alpha-ketoglutarate dehydrogenase; these latter enzymes are the mitochondrial target antigens of primary biliary cirrhosis. We report that 7 of the 96 patients reacted with the mitochondrial antigens that are prominent in primary biliary cirrhosis. Moreover, in those patients showing reactivity with mitochondrial antigens, the autoantibodies were directed at the same immunodominant epitopes that have been previously characterized in primary biliary cirrhosis. One of the 7 positive patients was known to have primary biliary cirrhosis. We hypothesize that the remaining 6 patients are at clinical risk for the development of primary biliary cirrhosis and/or that abnormalities would be found on liver biopsy.


The role of MyoD1 and histone modifications in the activation of muscle enhancers.
MyoD1 is a key regulator that orchestrates skeletal muscle differentiation through the regulation of gene expression. Although many studies have focused on its role in transcriptional control at gene promoters, less is known regarding the role of MyoD1 in the assembly of active enhancers. Here, we discuss novel data that point to the ability of MyoD1 to mediate the assembly of active enhancers that augment the transcription of genes essential for muscle development and lineage specification. Based on genome-wide studies of epigenetic marks that typify active enhancers, we recently identified the compendium of distal regulatory elements that dictate transcriptional programs during myogenesis. Superimposition of MyoD1 binding sites upon the locations of muscle enhancers revealed its unequivocal binding to a core region of nearly a third of condition-specific muscle enhancers. Further studies exploring deposition of enhancer-related epigenetic marks in myoblasts lacking MyoD1 demonstrate the dependence of muscle enhancer assembly on the presence of MyoD1. We propose a model wherein MyoD1 mediates recruitment of Set7, H3K4me1, H3K27ac, p300, and RNAP II to MyoD1-bound enhancers to establish condition-specific activation of muscle genes. Moreover, muscle enhancers are modulated through coordinated binding of transcription factors, including c-Jun, Jdp2, Meis, and Runx1, which are recruited to muscle enhancers in a MyoD1-dependent manner. Thus, MyoD1 and enhancer-associated transcription factors function coordinately to assemble and regulate enhancers, thereby augmenting expression of muscle-related genes.


Hereditary renal adysplasia.
A family with unilateral renal "agenesis" through 3 generations is presented. In two of the members, a small tissue bud with a ureteric remnant was observed, compatible with the syndrome of hereditary renal adysplasia. Small kidneys and small compensatory renal hypertrophy appear to be characteristic in this family.


Natural water defluoridation by adsorption on Laponite clay.
Safe drinking water is a necessity for every human being, but clean water is scarce and not easily available due to natural geochemical factors or industrial pollutant activity. Many issues involving water quality could be greatly improved using clays as adsorbents. We highlight for the first time, the uptake of fluoride from natural water by Laponite, synthetic hectorite clay, in raw and modified state. A series of batch adsorption experiments were carried out to evaluate the adsorption potential of the different parameters. The optimized parameters were: contact time, adsorbent dose and pH. It was found that fluoride uptake from natural water was better using raw Laponite and inorganic-modified Laponite than using organic-modified Laponite clays. Adsorbents were characterized before and after fluoride adsorption by X-ray diffraction, X-ray fluorescence, FTIR, thermo gravimetric analyses and 19F solid state NMR spectroscopy. The experimental data showed that both Langmuir and Freundlich models fitted an adsorption isotherm well. Thermodynamic parameters such as Gibbs free energy (ΔG°), enthalpy (ΔH°), and entropy (ΔS°) were calculated. These parameters indicated that fluoride adsorption onto Laponite was nonspontaneous and endothermic in temperature range between 25 and 45 °C.


An algorithm for identifying regions of a DNA sequence that satisfy a content requirement.
We present a dynamic programming algorithm for identifying regions of a DNA sequence that meet a user-specified compositional requirement. Applications of the algorithm include finding C + G-rich regions, locating TA + CG-deficient regions, identifying CpG islands, and finding regions rich in periodical three-base patterns. The algorithm has an advantage over the simple window method in that the algorithm shows the exact location of each identified region. The algorithm has been implemented as a portable C program called LCP (Local Content Program). LCP is extremely efficient in computer time and memory; it instantly locates all regions of a long DNA sequence meeting a given requirement. The LCP program was used to analyze the rabbit alpha-like globin gene cluster sequence.


Bridged adversarial training.
Adversarial robustness is considered a required property of deep neural networks. In this study, we discover that adversarially trained models might have significantly different characteristics in terms of margin and smoothness, even though they show similar robustness. Inspired by the observation, we investigate the effect of different regularizers and discover the negative effect of the smoothness regularizer on maximizing the margin. Based on the analyses, we propose a new method called bridged adversarial training that mitigates the negative effect by bridging the gap between clean and adversarial examples. We provide theoretical and empirical evidence that the proposed method provides stable and better robustness, especially for large perturbations.


Dermabrasion for showers of seborrheic keratoses.
Seborrheic keratoses, skin tumors of undetermined etiology, are easily traumatized with consequent local irritation and inflammation, and are cosmetically undesirable. They can occasionally undergo malignant degeneration. A rapid increase in size and number of these lesions is thought by many to be a sign of internal malignancy. Dermabrasion using a diamond fraise is a simple and fast method for removing multiple seborrheic keratoses with minimal trauma, rapid healing, and good cosmetic results.


What is the selection process for osteoarthritis pharmacotherapy?
Osteoarthritis is the most prevalent joint condition that continues to increase with an ever-aging population and the rising tide of obesity. There are multiple recommendations/guidelines for the management of osteoarthritis. The basis of management should focus on self-management and education, lifestyle modifications, exercise and when appropriate, weight loss. Pharmacotherapy is targeted toward pain palliation with no agents available presently to target prevention and disease modification. The selection of pharmacotherapy should be tailored to the individual, taking into account of personal preferences and interactions with underlying co-morbidities. This editorial provides a guide to the selection process of presently available pharmacotherapy in osteoarthritis.


Screening for asymptomatic bacteriuria in adults: evidence for the U.S. Preventive Services Task Force reaffirmation recommendation statement.
Asymptomatic bacteriuria is common, and screening for this condition in pregnant women is a well-established, evidence-based standard of current medical practice. Screening other groups of adults has not been shown to improve outcomes. To review new and substantial evidence on screening for asymptomatic bacteriuria, to support the work of the U.S. Preventive Services Task Force. English-language studies of adults (age >18 years) indexed in PubMed and the Cochrane Library and published from 1 January 2002 through 30 April 2007. For benefits of screening or treatment for screened populations, systematic reviews; meta-analyses; and randomized, controlled trials were included. For harms of screening, systematic reviews; meta-analyses; randomized, controlled trials; cohort studies; case-control studies; and case series of large multisite databases were included. Two reviewers independently reviewed titles, abstracts, and full articles for inclusion. Two reviewers extracted data from studies on benefits of screening and treatment (including decreases in the incidence of adverse maternal and fetal outcomes, symptomatic urinary tract infections, hypertension, and renal function decline). An updated Cochrane systematic review of 14 randomized, controlled trials of treatment supports screening for asymptomatic bacteriuria in pregnant women. A randomized, controlled trial and a prospective cohort study show that screening nonpregnant women with diabetes for asymptomatic bacteriuria is unlikely to produce benefits. No new evidence on screening men for asymptomatic bacteriuria or on harms of screening was found. The focused search strategy may have missed some smaller studies on the benefits and harms of screening for asymptomatic bacteriuria. The available evidence continues to support screening for asymptomatic bacteriuria in pregnant women, but not in other groups of adults.


Predictive biomarkers for the treatment of resectable esophageal and esophago-gastric junction adenocarcinoma: from hypothesis generation to clinical validation.
Esophageal and esophago-gastric junction (EGJ) adenocarcinomas remain a major health problem worldwide with a worryingly increasing incidence. Recent trials indicate survivals benefit for preoperative or perioperative chemoradiotherapy compared to surgery alone. Beside standard chemoradiotherapy regimens, new therapeutic approaches with targeted therapies have been proposed for the treatment of resectable disease. However, clinical outcomes remain extremely poor due to drug resistance phenomena. The failure of these approaches could be partially ascribed to their incorrect application in patients. Therefore, the identification of strong biomarkers for optimal patient management is urgently needed. Areas covered: This review aims to summarize and critically discuss the most relevant findings regarding predictive biomarker development for neoadjuvant treatment of resectable esophageal and esophago-gastric junction adenocarcinoma patients. Expert commentary: Optimizing the currently available therapeutic modalities through a more accurate selection of patients may avoid the use of ineffective and potentially toxic treatments. During the last decade, the advent of high-throughput '-omics' technologies has set the basis for a new biomarker discovery approach from 'molecule by molecule' screening towards a large-scale systematic screening process with exponential increases in putative biomarkers, which often failed to provide adequate clinical validation.


Modulation of lipid metabolism through multiple pathways during oocyte maturation and embryo culture in bovine.
Lipid accumulation occurs in cultured embryos and is associated with reduced cryotolerance. Here we report the use of a multiple pathway lipid modulator cocktail (l-carnitine, linoleic acid and forskolin) to improve cryosurvival. First, we stained oocytes and embryos with Oil Red to examine the time course of lipid accumulation during in vitro fertilization (IVF) and embryo culture. Then we evaluated the effects of the lipid modulators cocktail on lipid content, developmental rates and survival after vitrification. In our conditions, lipid accumulation was detected (P < 0.05) at the end of in vitro maturation (IVM) and after 4 days of embryo culture (D4-D5). In experiment 1, we used lipid modulator cocktail during IVM. Reduced (P < 0.05) lipid accumulation was detected in oocytes (Control: 49.9 ± 1.6, Lip. Mod. IVM: 45.0 ± 1.8) but no changes were present at blastocyst stage (Control: 62.4 ± 2.6, Lip. Mod. IVM: 66.8 ± 2.7). Treated oocytes presented decreased (P < 0.05) blastocyst rates and lower (P < 0.05) re-expansion after vitrification. In experiment 2, lipid modulators cocktail was used during embryo culture (from D4-D7 or D6-D7). Treatment had an effect on lipid metabolism, as lipid content was increased (P < 0.05) in D7 blastocysts in treated groups (Control: 52.7 ± 3.1a, D4: 65.9 ± 2.6b, D6: 78.1 ± 2.7b). However, no effect was present for cleavage, blastocyst and cryosurvival rates. No difference was detected in mean cell number comparing the three groups (Control: 78.9 ± 9.6, D4: 82.6 ± 16.5, D6: 68.3 ± 7.8), but apoptosis rate was increased (P < 0.05) in vitrified-warmed blastocysts from treated groups (Control: 14.77*, D4: 22.28, D6: 22.22). We concluded that the combined use of lipid modulators was efficient to promote changes in lipid content of oocytes and embryos in bovine, but those changes did not reflect positively on embryo development or cryosurvival.


Pharmacoeconomic Aspects of Diabetes Mellitus: Outcomes and Analysis of Health Benefits Approach.
Pharmacoeconomics is an important tool for investigating and restructuring healthcare policies. In India, recent statistical studies have shown that the number of diabetic patients is rapidly increasing in the rural, middle and upper-class settings. The aim of this review is to call attention towards the need to carry out pharmacoeconomic studies for diabetes mellitus and highlight the outcome of these studies on healthcare. A well-structured literature search from PubMed, Embase, Springer, ScienceDirect, and Cochrane was done. Studies that evaluated the cost-effectiveness of various anti-diabetic agents for type 2 diabetes were eligible for inclusion in the analysis and review. Two independent reviewers sequentially assessed the titles, abstracts, and full articles to select studies that met the predetermined inclusion and exclusion criteria for data abstraction. Any discrepancies between the reviewers were resolved through consensus. By employing search terms such as pharmacoeconomics, diabetes mellitus, cost-effective analysis, cost minimization analysis, cost-utility analysis, and cost-benefit analysis, a total of 194 papers were gathered. Out of these, 110 papers were selected as they aligned with the defined search criteria and underwent the removal of duplicate entries. This review outlined four basic pharmacoeconomic studies carried out on diabetes mellitus. It gave a direction that early detection, patient counseling, personalized medication, appropriate screening intervals, and early start of pharmacotherapy proved to be a cost-effective as well as health benefits approach.


The δ13C Value of Fingerstick Blood Is a Valid, Reliable, and Sensitive Biomarker of Sugar-Sweetened Beverage Intake in Children and Adolescents.
Reliance on self-reported dietary intake methods is a commonly cited research limitation, and dietary misreporting is a particular problem in children and adolescents. Objective indicators of dietary intake, such as dietary biomarkers, are needed to overcome this research limitation. The added sugar (AS) biomarker δ13C, which measures the relative abundance of 13C to 12C, has demonstrated preliminary validity in adults. The purpose of this investigation was to determine the comparative validity, test-retest reliability, and sensitivity of the δ13C biomarker to detect AS and sugar-sweetened beverage (SSB) intake using fingerstick blood samples in children and adolescents. Children (aged 6-11 y, n = 126, 56% male, mean ± SD age: 9 ± 2 y) and adolescents (aged 12-18 y, n = 200, 44% male, mean ± SD age: 15 ± 2 y) completed 4 testing sessions within a 3-wk period. Participants' height, weight, demographic characteristics, and health history were determined at the first session; 24-h recalls were obtained at each visit and fingerstick blood samples were collected at visits 1 and 3. Samples were analyzed for δ13C value using natural abundance stable isotope mass spectrometry. δ13C value was compared with dietary outcomes in the full sample, and in child and adolescent subgroups. t Tests and correlational analyses were used to assess biomarker validity and reliability, whereas logistic regression and area under the receiver-operator characteristic curve (AUC) were used to evaluate sensitivity. Reported mean ± SD AS consumption was 82.2 ± 35.8 g/d and 329 ± 143 kcal/d, and SSB consumption was 222 ± 243 mL/d and 98 ± 103 kcal/d. Mean δ13C value was -19.65 ± 0.69‰, and was lower in children than in adolescents (-19.80 ± 0.67‰ compared with -19.56 ± 0.67‰, P = 0.002). δ13C values were similar across sessions (visit 1: -19.66 ± 0.68‰; visit 3: -19.64 ± 0.68‰; r = 0.99, P < 0.001) and were associated (P < 0.001) with intake of total AS (grams, kilocalories: r = 0.29) and SSB (milliliters, kilocalories: r = 0.35). The biomarker was able to better discriminate between high and low SSB consumers than high and low AS consumers, as demonstrated by the AUC (0.75 and 0.62, respectively). The δ13C biomarker is a promising, minimally invasive, objective biomarker of SSB intake in children and adolescents. Further evaluation using controlled feeding designs is warranted. Registered at clinicaltrials.gov as NCT02455388.


Assessment of vitamin D status in Czech children.
Vitamin D deficiency is a global health problem. The aim of this study was to determine the proportion of Czech children with vitamin D deficiency and examine related factors. The study subjects were 419 healthy children aged 5 and 9 years. Severe vitamin D deficiency was defined as a serum 25(OH)D level of < 25 nmol/L (3% of children), deficiency as that of 25-50 nmol/L (24% of children), insufficiency as that of 50-75 nmol/L (40% of children) and sufficiency as that of > 75 nmol/L (34% of children). Serum 25(OH)D levels varied mainly with season. The highest levels of 25(OH)D were reached in autumn (median: 79.0 nmol/L), followed by summer (median: 67.8 nmol/L) and winter (median: 56.0 nmol/L). The lowest median value (49.8 nmol/L) was detected in spring. Children with sufficiency 25(OH)D levels were more frequently exposed to the sun and exposed a larger part of their body to the sun while spending time outdoors. Levels of 25(OH)D were also associated with using vitamin D supplements within six weeks before sampling.


Phyla nodiflora L. Extracts Induce Apoptosis and Cell Cycle Arrest in Human Breast Cancer Cell Line, MCF-7.
Phyla nodiflora L. has been used as medicinal remedies for various ailments due to its antioxidant, anti-inflammatory, anti-bacterial, anti-tumor activity. Previously, we found that the plant extracts induced DNA fragmentation in MCF-7. This study was to investigate the modes of action of P. nodiflora in inhibiting breast cancer cells using leaf ethyl acetate (EA leaf), stem ethyl acetate (EA stem) and stem methanol (Met stem) extracts. The MTT assay showed that the anti-proliferative effects of P. nodiflora extracts were selective towards MCF-7 with a minimal effect on MCF10A. Morphological changes such as cell shrinkage and nuclear condensation were observed in treated cells. We found that induction of apoptosis by EA leaf and EA stem was mitochondrial-dependent while loss of mitochondrial membrane potential was not found in Met stem-treated cells. In addition, the expression levels of AIFM1, CASP9, CFLAR, and IGF1R were altered after treatment. Decreased BCL-2 expression was found in treated cells while BAX and caspases' expression was upregulated or maintained. All extracts caused perturbation of cell cycle at S phase by dysregulating the expression of cell cycle regulators such as CDKs and cyclins. Our findings indicate that P. nodiflora inhibits MCF-7 cells by inducing apoptosis and perturbing cell cycle.


Robot-Assisted Hybrid Esophagectomy Is Associated with a Shorter Length of Stay Compared to Conventional Transthoracic Esophagectomy: A Retrospective Study.
To compare the peri- and postoperative data between a hybrid minimally invasive esophagectomy (HMIE) and the conventional Ivor Lewis esophagectomy. Retrospective comparison of perioperative characteristics, postoperative complications, and survival between HMIE and Ivor Lewis esophagectomy. 216 patients were included, with 160 procedures performed with the conventional and 56 with the HMIE approach. Lower perioperative blood loss was found in the HMIE group (600 ml versus 200 ml, p < 0.001). Also, a higher median number of lymph nodes were harvested in the HMIE group (median 28) than in the conventional group (median 23) (p = 0.002). The median length of stay was longer in the conventional group compared to the HMIE group (11.5 days versus 10.0 days, p = 0.03). Patients in the HMIE group experienced fewer grade 2 or higher complications than the conventional group (39% versus 57%, p = 0.03). The rate of all pulmonary (51% versus 43%, p = 0.32) and severe pulmonary complications (38% versus 18%, p = 0.23) was not statistically different between the groups. The HMIE was associated with lower intraoperative blood loss, a higher lymph node harvest, and a shorter hospital stay. However, the inborn limitations with the retrospective design stress a need for prospective randomized studies. Registration number is DRKS00013023.


The effects of L-arginine and iloprost on the viability of random skin flaps in rats.
The effects of an intravenous infusion of L-arginine as a physiological precursor of endothelium-derived relaxing factor/nitric oxide (EDRF/NO), iloprost (a stable prostacyclin (PGI2) analogue), and L-arginine combined with iloprost on skin viability were studied in 9 x 3 cm random pattern skin flaps in rats. Intravenous infusion of all drugs was started at the beginning of the operation and continued for 60 minutes. At the end of infusion period the depth of fluorescein dye penetration in the skin flap was assessed visually from photographic records, and the flap survival area was measured by the grid method at the seventh postoperative day. There was a significant reduction in distal necrosis of random skin flaps after intravenous infusion of L-arginine, iloprost, and L-arginine combined with iloprost (p < 0.01). Possible mechanisms that may be responsible for impairment of endothelium-dependent vasodilation and vasospasm in the microvasculature of random skin flap and their prevention with L-arginine and iloprost include restoration of the depleted stores of NO which in turn causes vasodilatation and has an antithrombotic effect.


First-principles study on unidirectional proton transfer on anatase TiO2 (101) surface induced by external electric fields.
The electric field (EF) effect on hydrogen or proton transfer (PT) via hydroxyl groups on an anatase TiO2 (101) surface is examined using first-principles density functional theory and the modern theory of polarization. This study focuses on unidirectional surface PT caused by external EFs at various orientations toward the surface. The preferred PT pathway can change depending on the magnitude and direction of the EF. Detailed analysis reveals that the variation in the energy profile with the EF is significantly different from that determined by the classical electric work of an EF carrying a point charge. The EF effect on the energy profile of the PT is governed by the rearrangement of the chemical bond network at the interface between the water molecules and the surface.


Fast gas chromatography and negative-ion chemical ionization tandem mass spectrometry for forensic analysis of cannabinoids in whole blood.
The present work describes a fast gas chromatography/negative-ion chemical ionization tandem mass spectrometric assay (Fast GC/NICI-MS/MS) for analysis of tetrahydrocannabinol (THC), 11-hydroxy-tetrahydrocannabinol (THC-OH) and 11-nor-9-carboxy-tetrahydrocannabinol (THC-COOH) in whole blood. The cannabinoids were extracted from 500 microL of whole blood by a simple liquid-liquid extraction (LLE) and then derivatized by using trifluoroacetic anhydride (TFAA) and hexafluoro-2-propanol (HFIP) as fluorinated agents. Mass spectrometric detection of the analytes was performed in the selected reaction-monitoring mode on a triple quadrupole instrument after negative-ion chemical ionization. The assay was found to be linear in the concentration range of 0.5-20 ng/mL for THC and THC-OH, and of 2.5-100 ng/mL for THC-COOH. Repeatability and intermediate precision were found less than 12% for all concentrations tested. Under standard chromatographic conditions, the run cycle time would have been 15 min. By using fast conditions of separation, the assay analysis time has been reduced to 5 min, without compromising the chromatographic resolution. Finally, a simple approach for estimating the uncertainty measurement is presented.


Combined in vivo and ex vivo analysis of mesh mechanics in a porcine hernia model.
Hernia meshes exhibit variability in mechanical properties, and their mechanical match to tissue has not been comprehensively studied. We used an innovative imaging model of in vivo strain tracking and ex vivo mechanical analysis to assess effects of mesh properties on repaired abdominal walls in a porcine model. We hypothesized that meshes with dissimilar mechanical properties compared to native tissue would alter abdominal wall mechanics more than better-matched meshes. Seven mini-pigs underwent ventral hernia creation and subsequent open repair with one of two heavyweight polypropylene meshes. Following mesh implantation with attached radio-opaque beads, fluoroscopic images were taken at insufflation pressures from 5 to 30 mmHg on postoperative days 0, 7, and 28. At 28 days, animals were euthanized and ex vivo mechanical testing performed on full-thickness samples across repaired abdominal walls. Testing was conducted on 13 mini-pig controls, and on meshes separately. Stiffness and anisotropy (the ratio of stiffness in the transverse versus craniocaudal directions) were assessed. 3D reconstructions of repaired abdominal walls showed stretch patterns. As pressure increased, both meshes expanded, with no differences between groups. Over time, meshes contracted 17.65% (Mesh A) and 0.12% (Mesh B; p = 0.06). Mesh mechanics showed that Mesh A deviated from anisotropic native tissue more than Mesh B. Compared to native tissue, Mesh A was stiffer both transversely and craniocaudally. Explanted repaired abdominal walls of both treatment groups were stiffer than native tissue. Repaired tissue became less anisotropic over time, as mesh properties prevailed over native abdominal wall properties. This technique assessed 3D stretch at the mesh level in vivo in a porcine model. While the abdominal wall expanded, mesh-ingrown areas contracted, potentially indicating stresses at mesh edges. Ex vivo mechanics demonstrate that repaired tissue adopts mesh properties, suggesting that a better-matched mesh could reduce changes to abdominal wall mechanics.


Depression and HIV risk behavior practices among at risk women.
In this study, we examined the relationship between depression and HIV-related risk behavior practices in a sample of 250 at risk, predominantly African American women living in the Atlanta, Georgia metropolitan area. Interviews were conducted between August 1997 and August 2000. Street outreach efforts were used to identify potential study participants, with further expansion of the sample via targeted sampling and ethnographic mapping procedures. Our conceptual model hypothesized a relationship between depression and HIV risk in which depression and condom-related attitudes were construed as intervening (or mediating) variables. A multivariate analysis was used to determine the relationship between depression and women's risk behaviors. The results showed that depression was a key-mediating variable, having its primary influence on women's risky practices through its impact upon their attitudes toward using condoms. Factors associated with depression, included religiosity, closeness of family relationships, financial problems, childhood maltreatment experiences, and drug-related problems. The implications of these findings for prevention and intervention efforts are: (1) heightening faith community involvement and religious participation to decrease depression; (2) working with women whose familial bonds are in need of strengthening to combat depression; (3) providing mental health and counseling services to women who were emotionally and/or sexually abused during their formative years seems to help these women to recover from unresolved issues that may be fueling depression; (4) assisting at risk women who need training in money management issues to minimize their risk for depression; and (5) helping women drug abusers to receive treatment for their drug problems to combat their depression and lower their HIV risk.


Event-specific quantitative detection of nine genetically modified maizes using one novel standard reference molecule.
With the development of genetically modified organism (GMO) detection techniques, the Polymerase Chain Reaction (PCR) technique has been the mainstay for GMO detection, and real-time PCR is the most effective and important method for GMO quantification. An event-specific detection strategy based on the unique and specific integration junction sequences between the host plant genome DNA and the integrated gene is being developed for its high specificity. This study establishes the event-specific detection methods for TC1507 and CBH351 maizes. In addition, the event-specific TaqMan real-time PCR detection methods for another seven GM maize events (Bt11, Bt176, GA21, MON810, MON863, NK603, and T25) were systematically optimized and developed. In these PCR assays, the fluorescent quencher, TAMRA, was dyed on the T-base of the probe at the internal position to improve the intensity of the fluorescent signal. To overcome the difficulties in obtaining the certified reference materials of these GM maizes, one novel standard reference molecule containing all nine specific integration junction sequences of these GM maizes and the maize endogenous reference gene, zSSIIb, was constructed and used for quantitative analysis. The limits of detection of these methods were 20 copies for these different GM maizes, the limits of quantitation were about 20 copies, and the dynamic ranges for quantification were from 0.05 to 100% in 100 ng of DNA template. Furthermore, nine groups of the mixed maize samples of these nine GM maize events were quantitatively analyzed to evaluate the accuracy and precision. The accuracy expressed as bias varied from 0.67 to 28.00% for the nine tested groups of GM maize samples, and the precision expressed as relative standard deviations was from 0.83 to 26.20%. All of these indicated that the established event-specific real-time PCR detection systems and the reference molecule in this study are suitable for the identification and quantification of these GM maizes.


Relation of coronary artery stenosis and pressure gradient to exercise-induced ischemia before and after coronary angioplasty.
The purpose of this investigation was to evaluate the relation of coronary artery stenosis and associated pressure gradient to the magnitude of exercise-induced left ventricular dysfunction in patients with single vessel coronary artery disease. The percent stenosis and minimal cross-sectional area were measured before and after percutaneous transluminal coronary angioplasty and compared with radionuclide measurements of left ventricular function before and after angioplasty in 41 patients with proximal left anterior descending coronary artery lesions, providing 82 points of comparison. The gradient could be measured for 75 comparisons. Forty stenoses less than 50% were associated with a mean left ventricular exercise ejection fraction of 0.66 +/- 0.08 (mean +/- SD), 25 stenoses from 50 to 75% with a mean ejection fraction of 0.59 +/- 0.12 and 17 stenoses greater than 75% with a mean ejection fraction of 0.49 +/- 0.08. Thirty-five stenoses with a gradient less than 20 mm Hg were associated with a mean ejection fraction of 0.65 +/- 0.09, 24 with a gradient from 20 to 50 mm Hg with a mean ejection fraction of 0.58 +/- 0.13 and 16 with a gradient greater than 50 mm Hg with a mean ejection fraction of 0.53 +/- 0.10. These data document a relation between the magnitude of coronary artery stenosis and associated gradient to exercise-induced left ventricular dysfunction in homogeneous patient groups. However, discordance of these variables occurs commonly in individual patients.


Investigating physiological glucose excursions before, during, and after Ramadan in adults without diabetes mellitus.
The study aimed to investigate physiological effects of Ramadan fasting on continuously monitored glucose levels in relation to Ramadan in young non-diabetic adults. Continuous glucose monitoring was employed to measure interstitial glucose for several days 1-2weeks before Ramadan, in the middle of Ramadan, and 4-6weeks after Ramadan to assess glucose exposure and glucose variability. A total of 34,182 accurate glucose sensor readings and 438 capillary blood glucose values [mean absolute difference median (interquartile range) 8.5 (6.9-11.1)%] were obtained from 18 non-diabetic adults [13 females; aged 24 (21-27) years; baseline body mass index 23.9 (20.6-28.9) kg/m2]. The continuous glucose monitoring profiles showed an increase in the hyperglycemic (above 140mg/dL) area under the curve after Ramadan compared to both before (P=0.004) and during Ramadan (P=0.003), along with an increased glucose variability after Ramadan (P=0.014). Both the area under the interstitial glucose concentration curve for the entire day and the average glucose were positively associated with body mass index during (P=0.004 and P=0.005, respectively) and after Ramadan (P=0.013 and P=0.01, respectively). Atypical continuous glucose patterns were recognized in 11% of subjects, distinguished by a prolonged increased glucose exposure, particularly in response to a meal. The time-point 4-6weeks after Ramadan was distinguished by greater glucose exposure and wider glucose variability that may reflect ongoing changes in insulin sensitivity in response to altering lifestyle patterns in non-diabetic young adults across the spectrum of body weight.


Prevalence, consequences and prevention of childhood nutritional iron deficiency: a child public health perspective.
The true extent of nutritional iron deficiency (ID) in childhood is unclear because of uncertainty over its definition and the insensitivity of markers of ID. The major cause is likely to be the excessive and early use of cow's milk. Recent neurophysiological observations support the many field studies correlating ID with cognitive developmental delays. Prevention is best sought through supplementation of essential foods.


The Preparation and Identification of a Monoclonal Antibody against Citrinin and the Development of Detection via Indirect Competitive ELISA.
Citrinin (CTN) is a hepato-nephrotoxic mycotoxin produced by fungi genera of Aspergillus, Monauscus, and Penicillium. CTN contaminates grains, fruits, juices and vegetables, and causes various toxic effects to humans and animals. It has small molecular weight, which is non-immunogenic to animals. Thus, CTN was conjugated to bovine serum albumin (BSA) and ovalbumin (OVA), respectively, by amide bonds using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). Mice were immunized with CTN-BSA conjugates, and spleen cells of the immunized mice were fused with Sp2/0 myeloma cells to obtain 21H27 hybriodoma cell. Ascitic fluid of hybridoma cell was produced in mice abdomen, and purified using caprylic/ammonium sulfate precipitation method. The 21H27 anti-CTN mcAb was the IgG2a antibody subclass, and cross-reactivity results indicated that anti-CTN mcAb is specific to CTN with high affinity (2.0 × 10⁸ L/mol). Indirect competitive ELISA (ic-ELISA) results showed that the linear range of detection was 0.01-5.96 ng/mL and the IC50 was 0.28 ng/mL with a lower detection limit (LOD) of 0.01 ng/mL. The average recovery was 93.8% ± 1.6% with a coefficient variation of 1.0%-4.3%. Hence, anti-CTN mcAb secreted by 21H27 hybridoma cell was successfully produced and can be used to detect CTN contaminated feed and foodstuffs.


The dynamic changes of mango (Mangifera indica L.) epicuticular wax during fruit development and effect of epicuticular wax on Colletotrichum gloeosporioides invasion.
Mango fruits are susceptible to diseases, such as anthracnose, during fruit development, leading to yield reduction. Epicuticular wax is closely related to resistance of plants to pathogenic bacterial invasion. In this study, the effect of mango fruit epicuticular wax on the invasion of Colletotrichum gloeosporioides was investigated, followed by to understand the changes of wax chemical composition and crystal morphology during mango fruit development using GC-MS and SEM. Results showed that the epicuticular wax of mango fruits can prevent the invasion of C. gloeosporioides, and 'Renong' showed the strongest resistance to C. gloeosporioides. The wax content of four mango varieties first increased and then decreased from 40 days after full bloom (DAFB) to 120 DAFB. In addition, 95 compounds were detected in the epicuticular wax of the four mango varieties at five developmental periods, in which primary alcohols, terpenoids and esters were the main wax chemical composition. Furthermore, the surface wax structure of mango fruit changed dynamically during fruit development, and irregular platelet-like crystals were the main wax structure. The present study showed the changes of wax content, chemical composition and crystal morphology during mango fruit development, and the special terpenoids (squalene, farnesyl acetate and farnesol) and dense crystal structure in the epicuticular wax of 'Renong' fruit may be the main reason for its stronger resistance to C. gloeosporioides than other varieties. Therefore, these results provide a reference for the follow-up study of mango fruit epicuticular wax synthesis mechanism and breeding.


The use and mechanism of action of intravenous immunoglobulin in the treatment of immune haematologic disease.
In summary, intravenous gammaglobulin appears to be a very useful treatment of immune haematologic disease. Almost all patients with ITP treated with IVIg will have an increase in their platelet counts lasting at least 2 weeks. Some of these patients will derive long-term benefit from the IVIg and many can maintain their platelet counts by periodic single outpatient infusions. Patients with immune neutropenia are also likely to benefit by IVIg treatment which may be of particular benefit due to its not interfering with phagocyte function. RES blockade is a well-documented mechanism of action immediately after IVIg infusion and platelet antibody synthesis may decrease in some patients; IVIg does not appear to protect platelets from platelet antibodies.


Coeliac disease in Type 1 diabetes from 1990 to 2009: higher incidence in young children after longer diabetes duration.
To determine the incidence of coeliac disease in young people with Type 1 diabetes and to examine the effect of age at diabetes onset and disease duration. This was a clinic-based observational cohort study of 4379 people aged ≤ 18 years (49% male) between 1990 and 2009 from Sydney, Australia. Screening for coeliac disease was performed at diagnosis and 1-2 yearly using anti-endomysial and/or anti-tissue transglutaminase immunoglobulin A (IgA) antibodies. Coeliac disease was diagnosed by small bowel biopsy based on Marsh score ≥ III. Coeliac disease was confirmed by biopsy in 185; of these, 61 (33%) were endomysial or tissue transglutaminase IgA antibody-positive at diabetes diagnosis. Mean age at diabetes onset was 6.6 ± 4.0 vs. 8.4 ± 4.1 years in those without coeliac disease (P < 0.001). Mean incidence was 7.7 per 1000 person years (95% CI 6.6-8.9) over 20 years. Incidence was higher in children aged < 5 years at diabetes diagnosis (10.4 per 1000 person years) vs. ≥ 5 years (6.4 per 1000), incidence rate ratio 1.6 (95% CI 1.2-2.2, P = 0.002). Coeliac disease was diagnosed after 2, 5 and 10 years of diabetes in 45, 78 and 94% of cases, respectively. Median time to coeliac disease diagnosis was longer in children aged < 5 years at diabetes onset (3.3 years) compared with older children (0.7 years, P < 0.001). Coeliac disease is common in young people with Type 1 diabetes; the risk is greatest with diabetes onset < 5 years, but after longer diabetes duration. Screening for coeliac disease should be performed at diabetes diagnosis and for at least 10 years in young children.


Fast decision in favor of the slow fission process.
The fission probability P(f) of highly excited targetlike nuclei produced in reactions of 2.5 GeV protons on Au, Bi, and U was studied as a function of excitation energy E* whereby E* is deduced eventwise from the multiplicity of evaporated light particles. At the highest E* of 1000 MeV P(f) amounts to approximately 30% with all 3 target nuclei irrespective of the initial fissility. Statistical-model calculations satisfactorily reproduce the observed evolution of P(f) with E*--provided that no extra transient delay is introduced. Fission thus is decided upon very fast and early in the long deexcitation chain towards scission which comprises as much as approximately 80% of all evaporated alpha particles.


Multimodal Hallucinations in Schizophrenia and Its Management.
A cluster of symptoms including hallucinations characterizes schizophrenia. Hallucinations that occur in more than one modality simultaneously and emanate from a single source are called multimodal hallucinations (MMHs). The occurrence of simultaneous hallucinations as the major manifestations of a psychiatric disorder often was dismissed as factitious disorder or malingering. Conversely, MMHs have been reported in severe mental disorders including schizophrenia. Here, we report MMH in two patients of treatment-resistant schizophrenia and its successful management with clozapine. The significance of MMH on the course, prognosis, and treatment resistance of schizophrenia needs to be elucidated. Further systematic research is needed to address these issues.


Instability in magnetic materials with a dynamical axion field.
It has been pointed out that axion electrodynamics exhibits instability in the presence of a background electric field. We show that the instability leads to a complete screening of an applied electric field above a certain critical value and the excess energy is converted into a magnetic field. We clarify the physical origin of the screening effect and discuss its possible experimental realization in magnetic materials where magnetic fluctuations play the role of the dynamical axion field.


Pregnancy in the brown Norway rat: a model for investigating the genetics of placentation.
The placenta facilitates the exchange of nutrients and wastes in an effort to promote fetal development. Disruptions in the establishment of the placenta and its interactions with the maternal uterus are potential causes of pregnancy failure. In this study we investigated the pregnancy phenotype of two inbred rat strains: the Dahl Salt Sensitive (DSS) strain and the Brown Norway (BN) strain. The DSS strain is reported to have large litters, whereas the BN strain has small litters. Pregnant female rats of each strain were killed on various days of gestation. At the time of killing, the number of viable versus dead and/or resorbing conceptuses was determined. Placental tissues from viable conceptuses were collected and processed for biochemical and histologic analyses. The number of viable conceptuses at Days 8.5 and 18.5 of gestation was significantly greater in DSS versus BN rats. Additionally, the number of resorbing and/or dying conceptuses was significantly greater in the BN strain than in the DSS strain. Maternal responses to pregnancy and elements of placental and fetal development in DSS and BN rats differed. Immunohistologic analysis of placentation and gene expression profiles revealed that trophoblast cell invasion into the uterine mesometrial compartment was significantly less in the BN strain versus the DSS strain. In contrast, the uterine natural killer cell population was reciprocally expanded in the BN strain. The impairment in trophoblast cell invasion in BN rats was associated with a smaller junctional zone compartment of the chorioallantoic placenta. Collectively, the data indicate that BN rats exhibit a unique form of placentation and may represent an excellent model for investigating the genetics of placental development.


Economic viability of phytoremediation of a cadmium contaminated agricultural area using energy maize. Part I: effect on the farmer's income.
This paper deals with the economic viability of using energy maize as a phytoremediation crop in a vast agricultural area moderately contaminated with metals. The acceptance of phytoremediation as a remediation technology is, besides the extraction rate, determined by its profitability, being the effects it has on the income of the farmer whose land is contaminated. This income can be supported by producing renewable energy through anaerobic digestion of energy maize, a crop that takes up only relatively low amounts of metals, but that can be valorised as a feedstock for energy production. The effect on the income per hectare of growing energy maize instead of fodder maize seems positive, given the most likely values of variables and while keeping the basic income stable, originating from dairy cattle farming activities. We propose growing energy maize aiming at risk-reduction, and generating an alternative income for farmers, yet in the long run also generating a gradual reduction of the pollution levels. In this way, remediation is demoted to a secondary objective with sustainable risk-based land use as primary objective.


Na-ctl-2, a cDNA encoding a C-type lectin expressed exclusively in adult Necator americanus hookworms.
C-type lectins (C-TLs) are carbohydrate-binding proteins central to diverse physiological processes including immunity, venom-induced haemostasis and wound repair. Here we describe the cloning of Na-ctl-2, a cDNA encoding a secreted C-TL from the human hookworm Necator americanus. The transcript was detected in mRNA from adult worms but not infective larvae. The cDNA encoded an N-terminal secretory signal peptide followed by a long-form C-TL domain with sequence similarity to C-TL-like proteins from Caenorhabditis elegans and mammalian antigen presenting cell receptors, suggesting that hookworms might utilise this class of lectin to interrupt anti-parasite immune responses or interfere with host clotting mechanisms. This is the first report of a full-length cDNA encoding a lectin from hookworms. The unusually skewed representation of this protein family within different nematode genera and its subsequent impact on the evolution of nematode parasitism is discussed.


[Experience with EK-birthing chair (author's transl)].
A birthing chair with a rigid plastic seat was tested for usefulness and safety. The birthing chair was evaluated positively by the delivering patients. The obstetric team was convinced of the advantages of the sitting position for delivery at the end of the evaluation. Minor disadvantages such as increased soiling of the chair were accepted for the advantages. The tested birthing chair impedes operative deliveries from the perineal floor. These may become necessary unexpectedly during the second stage of labor. Under these circumstances the patient must be transferred to a conventional delivery table. This is psychologically and from a standpoint of the work load very disadvantageous. Therefore the EK-birthing chair is of limited usefulness in routine obstetrics. An ideal birthing chair in our opinion is a delivery bed which can be changed into a sitting position and into all intermediate positions between sitting and recumbent.


Identification of a non-junction phosphodiester that influences an autolytic processing reaction of RNA.
Oligoribonucleotides with specific sequences derived from the satellite RNA of tobacco ringspot virus undergo autolytic cleavage at the CpA phosphodiester that is the junction between unit sequences of multimeric satellite RNA. Buzayan et al. (Nucleic Acids Res., 16, 4009-4023 (1988)) showed that an oligoribonucleotide with 97 satellite RNA-derived nucleotide residues self-cleaved with greatly reduced efficiency when it was synthesized in vitro from adenosine-5'-O-(1-thiotriphosphate) (abbreviated rATP alpha S) and three rNTPs. No other substitution of one rNTP by the corresponding rNTP alpha S had this effect, suggesting that a phosphorothioate CpA junction inhibits self-cleavage. Here, we replaced the usual CpA junction of a small self-cleaving oligoribonucleotide with a CpU junction. Self-cleavage of this molecule was reduced not only by rUTP alpha S-substitution, as expected, but also by partial and complete rATP alpha S-substitution. By analysis of the locations of rAMPS residues in cleavage products derived from partially rATP alpha S-substituted oligoribonucleotides, we identified A26 as the residue contributing the non-junction phosphorothioate diester that most strongly inhibited self-cleavage. Manganese ions strongly stimulated the self-cleavage of the rATP alpha S-substituted, CpU-junction oligoribonucleotide but was less effective when the junction was CpA.


Biotransformation of irbesartan in man.
The metabolism of irbesartan, a highly selective and potent nonpeptide angiotensin II receptor antagonist, has been investigated in humans. An aliquot of pooled urine from healthy subjects given a 50-mg oral dose of [14C]irbesartan was added as a tracer to urine from healthy subjects that received multiple, 900-mg nonradiolabeled doses of irbesartan. Urinary metabolites were isolated, and structures were elucidated by mass spectroscopy, proton NMR, and high-performance liquid chromatography (HPLC) retention times. Irbesartan and the following eight metabolites were identified in human urine: (1) a tetrazole N2-beta-glucuronide conjugate of irbesartan, (2) a monohydroxylated metabolite resulting from omega-1 oxidation of the butyl side chain, (3, 4) two different monohydroxylated metabolites resulting from oxidation of the spirocyclopentane ring, (5) a diol resulting from omega-1 oxidation of the butyl side chain and oxidation of the spirocyclopentane ring, (6) a keto metabolite resulting from further oxidation of the omega-1 monohydroxy metabolite, (7) a keto-alcohol resulting from further oxidation of the omega-1 hydroxyl of the diol, and (8) a carboxylic acid metabolite resulting from oxidation of the terminal methyl group of the butyl side chain. Biotransformation profiles of pooled urine, feces, and plasma samples from healthy male volunteers given doses of [14C]irbesartan were determined by HPLC. The predominant drug-related component in plasma was irbesartan (76-88% of the plasma radioactivity). None of the metabolites exceeded 9% of the plasma radioactivity. Radioactivity in urine accounted for about 20% of the radiolabeled dose. In urine, irbesartan and its glucuronide each accounted for about 5 to 10% of the urinary radioactivity. The predominant metabolite in urine was the omega-1 hydroxylated metabolite, which constituted about 25% of the urinary radioactivity. In feces, irbesartan was the predominant drug-related component (about 30% of the radioactivity), and the primary metabolites were monohydroxylated metabolites and the carboxylic acid metabolite. Irbesartan and these identified metabolites constituted 90% of the recovered urinary and fecal radioactivity from human subjects given oral doses of [14C]irbesartan.


Characterizing roots and water uptake in a ground cover rice production system.
Water-saving ground cover rice production systems (GCRPS) are gaining popularity in many parts of the world. We aimed to describe the characteristics of root growth, morphology, distribution, and water uptake for a GCRPS. A traditional paddy rice production system (TPRPS) was compared with GCRPS in greenhouse and field experiments. In the greenhouse, GCRPS where root zone average soil water content was kept near saturation (GCRPSsat), field capacity (GCRPSfwc) and 80% field capacity (GCRPS80%), were evaluated. In a two-year field experiment, GCRPSsat and GCRPS80% were applied. Similar results were found in greenhouse and field experiments. Before mid-tillering the upper soil temperature was higher for GCRPS, leading to enhanced root dry weight, length, surface area, specific root length, and smaller diameter of roots but lower water uptake rate per root length compared to TPRPS. In subsequent growth stages, the reduced soil water content under GCRPS caused that the preponderance of root growth under GCRPSsat disappeared in comparison to TPRPS. Under other GCRPS treatments (GCRPSfwc and GCRPS80%), significant limitation on root growth, bigger root diameter and higher water uptake rate per root length were found. Discrepancies in soil water and temperature between TPRPS and GCRPS caused adjustments to root growth, morphology, distribution and function. Even though drought stress was inevitable after mid-tillering under GCRPS, especially GCRPS80%, similar or even enhanced root water uptake capacity in comparison to TPRPS might promote allocation of photosynthetic products to shoots and increase water productivity.


Patients undergoing dialysis therapy for 30 years or more survive with serious osteoarticular disorders.
Increasing numbers of patients are undergoing long-term dialysis therapy. It is crucial for their quality of life to overcome dialysis-related complications, such as dialysis-related amyloidosis (DRA) and other osteoarticular disorder. The aim of the study was to investigate the characteristics, such as dialysis-related complications, in chronic kidney disease (CKD) Stage 5D patients undergoing dialysis therapy for more than 30 years or more. From 2003 to 2006, 359 CKD Stage 5D patients who were admitted to a single tertiary-care center. The age and the duration of dialysis therapy, the purpose for hospital admission, and history of osteoarticular disorder, such as carpal tunnel syndrome (CTS), destructive spondyloarthropathy (DSA) and joint arthropathy, were studied. The proportions of the patients undergoing dialysis therapy for 20 - 24, 25 - 29 years and 30 years or more were 8.9, 5.6, and 4.5% of all admitted patients, respectively. DSA was a major cause of hospital admissions in long-term dialysis patients, especially in those treated for 30 years or more. The rate of surgery for osteoarticular disorder, such as CTS, DSA and joint arthropathy, which may show the presence of DRA, was 25.0, 66.0 and 77.8% in 20 - 24 years, 25 - 29 years and 30 years or more after the initiation of dialysis therapy, respectively. The frequency and severity of osteoarticular disorder accelerated with the duration of dialysis therapy, especially in those treated for 30 years or more. The rate of parathyroidectomy for secondary hyperparathyroidism was performed for 37.5% in 22.1 +/- 2.1 years after the initiation of dialysis treatment in the patients treated for 30 years or more. Mean age at the initiation of dialysis therapy was 27.3 +/- 8.0 years, and primary cause of CKD was mainly chronic glomerulonephritis in the patients undergoing dialysis therapy for 30 years or more. CKD stage 5D patients undergoing dialysis therapy for 30 years or more survive with characteristics of younger age at initiation of dialysis therapy, chronic glomerulonephritis as a primary cause of CKD, and serious complication of osteoarticular disorders.


An investigation into the use of thermorheology and texture analysis in the evaluation of W/O creams stabilized with a silicone emulsifier.
The aim of the study was to evaluate a range of W/O semisolid emulsion systems (creams) containing white soft paraffin (petrolatum) and a new type of nonionic lipophilic silicone emulsifier (Abil EM 90) using a novel combination of rheological tests. Emulsifier concentrations from 1.5% to 3.0% w/w were used with two manufacturing procedures, cold (25 degrees C) and warm (70 degrees C) emulsification, to determine whether and to what extent these variables alter the structure and consistency of the creams. The techniques comprised linear (continuous flow) and dynamic (oscillatory) rheometry at 25 degrees C, thermal flow experiments (from 10 degrees to 90 degrees C and back to 10 degrees C), and penetrometry studies. The differences in emulsifier concentration produced effects on the rheological properties of the W/ O creams, although the manufacturing process was much more influential. Cold emulsification led to creams with higher viscosity, lower thixotropy, and better elastic properties. The results of penetration tests on creams correlated with those of the rheological studies. The flow properties of white soft paraffin at 25 degrees C were comparable with the creams obtained by cold emulsification, while the elasticity was considerably lower. Thermorheological studies showed evidence for transitional behavior for white soft paraffin on heating, but not for the creams. White soft paraffin showed a higher viscosity (and resistance to the penetrating force) when melted at 70 degrees C and left to solidify at room temperature, compared to the "unmelted" sample. This was the opposite trend to that found with warm and cold emulsified creams. The input of heat during the emulsification process showed a strong effect on the structure and consistency of the W/O creams containing petrolatum and silicone emulsifier, resulting in a less viscous product. The use of the aforementioned techniques represents a useful and novel approach to the evaluation of cream consistency.


Changes in Aqueous Cytokine Levels Following Intravitreal Aflibercept in Treatment-Naive Patients with Diabetic Macular Edema.
Purpose: To investigate the changes in aqueous humor cytokine levels in response to short-term aflibercept therapy in treatment-naive patients with center-involving diabetic macular edema (DME). Methods: This is a prospective cohort study that included patients with treatment-naive DME with central subfield macular thickness ≥310 μm on optical coherence tomography from July 2015 to May 2017. Patients received 3 monthly intravitreal aflibercept injections. Aqueous samples for cytokine analysis were obtained before the first and third injections. Levels of various cytokines were measured using multiplex immunoassay. Main outcome measures were changes in aqueous cytokine levels from baseline to month 2. Results: A total of 17 patients were enrolled and 16 completed the study. The mean age was 57.2 ± 8.1 years. The following cytokines were significantly higher at month 2 versus baseline: transforming growth factor-beta (TGF-β)1 (P = 0.004), TGF-β2 (P = 0.017), inducible protein (IP)-10 (P = 0.011), and hepatocyte growth factor (HGF) (P = 0.02). There were significant reductions in the levels of vascular endothelial growth factor (VEGF) (P < 0.001), placental growth factor (PlGF) (P = 0.028), interleukin (IL)-6 (P = 0.011), and platelet-derived growth factor-AA (PDGF-AA) (P = 0.003). Conclusions: In treatment-naive patients with DME, short-term aflibercept therapy not only results in VEGF and PlGF suppression, but also leads to reduced levels of IL-6 and PDGF-AA and higher concentrations of TGF-β1, TGF-β2, HGF, and IP-10.


Proposal of a Linear Retention Index System for Improving Identification Reliability of Triacylglycerol Profiles in Lipid Samples by Liquid Chromatography Methods.
The retention index system was proposed in 1958 by Kováts. It is based on the correlation between the retention time of the analytes and the ones of a series of reference standards, making retention data dependent on the chromatographic phenomenon only, viz., on the three-term interaction analyte-stationary phase-mobile phase. Particularly in GC, because the mobile phase has a negligible influence, the retention of the analytes depends almost entirely on the stationary phase and it is as independent as possible from operating conditions. This makes retention index databases usable in samples identification at both the intra- and interlaboratory levels. The scope of this research was to create a similar identification system in LC, where the identification of unknowns is still a challenge because of the unavailability of spectral databases related to the low reproducibility of mass spectra generated by means of the atmospheric pressure ionization technique normally interfaced to LC. Lipid compounds, specifically triacylglycerols, were selected as target analytes mainly due to their regular chromatographic LC profile under reversed phase conditions. The odd carbon chain number triacylglycerol series from trinonain to trinonadecanoin was chosen as the basis of the retention index scale and a database of 209 triacylglycerols was built. For this purpose an ultra high-performance LC method, able to maximize the baseline separation of triacylglycerols in different real-world samples (vegetable oils, fish, and milk samples) was developed.


[Ten questions about eosinophilic myocarditis].
Eosinophilic myocarditis is a rare form of myocardial inflammation characterized by interstitial infiltration by eosinophils. Clinical presentation may vary from complete absence of symptoms to fulminant myocarditis with cardiogenic shock, to chronic heart failure due to progression to restrictive cardiomyopathy. The main causes of eosinophilic myocarditis are hypersensitivity reactions secondary to drug exposure, eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome and infections. Antibiotics and agents acting on the central nervous system are the most frequently reported drugs capable of causing hypersensitivity myocarditis. Infections are usually due to intestinal parasites. Imaging techniques together with clinical and laboratory data help rising the suspicion of eosinophilic myocarditis. However, the definite diagnosis is made by endomyocardial biopsy. The evidence of eosinophilic infiltrate among myocytes allows to start an immunosuppressive treatment, usually based on corticosteroids, that are the cardinal therapy for eosinophilic myocarditis. Anticoagulation should be undertaken in case of endoventricular thrombosis, which frequently complicates eosinophilic myocarditis, mainly those cases associated with hypereosinophilic syndrome and eosinophilic granulomatosis with polyangiitis. In this focused review, we will try to provide answers to the most common questions on the causes, presentation, diagnosis, treatment, and outcomes of eosinophilic myocarditis.


Errors in quantitative T1rho imaging and the correction methods.
The spin-lattice relaxation time constant in rotating frame (T1rho) is useful for assessment of the properties of macromolecular environment inside tissue. Quantification of T1rho is found promising in various clinical applications. However, T1rho imaging is prone to image artifacts and quantification errors, which remains one of the greatest challenges to adopt this technique in routine clinical practice. The conventional continuous wave spin-lock is susceptible to B1 radiofrequency (RF) and B0 field inhomogeneity, which appears as banding artifacts in acquired images. A number of methods have been reported to modify T1rho prep RF pulse cluster to mitigate this effect. Adiabatic RF pulse can also be used for spin-lock with insensitivity to both B1 RF and B0 field inhomogeneity. Another source of quantification error in T1rho imaging is signal evolution during imaging data acquisition. Care is needed to affirm such error does not take place when specific pulse sequence is used for imaging data acquisition. Another source of T1rho quantification error is insufficient signal-to-noise ratio (SNR), which is common among various quantitative imaging approaches. Measurement of T1rho within an ROI can mitigate this issue, but at the cost of reduced resolution. Noise-corrected methods are reported to address this issue in pixel-wise quantification. For certain tissue type, T1rho quantification can be confounded by magic angle effect and the presence of multiple tissue components. Review of these confounding factors from inherent tissue properties is not included in this article.


Osteoporosis in men.
The subject of osteoporosis in men is gaining international attention because it has become a significant public health issue. Women have been the focus of osteoporosis research for decades, and the majority of published data related only to women until recently. There is now significant research available supporting the importance of prevention and treatment of osteoporosis in men. This article addresses the spectrum of assessment, prevention, and treatment of this problem.


[The renal artery and uterine circulation in normal and toxemic pregnancies].
The renal and uterine arteries of 52 patients with normal course of pregnancy and 12 patients with EPH gestosis were examined by Doppler sonography between the 35th and 38th weeks of gestation post menstruationem. Doppler curves of renal arteries were recorded in a further 31 nonpregnant subjects. A significant difference in arterial vessel resistance was found between patients with normal course of pregnancy and those with EPH gestosis. There was also a significant difference in the circulation parameters in the renal vessels between patients with normal courses of pregnancy and the nonpregnant controls. However, there were no differences in this vessel segment between the patients with EPH gestosis and the nonpregnant controls. Among patients with EPH gestosis the renal increase in resistance was relatively more pronounced than the uterine increase. In addition to the calculated flow parameters there were also marked differences in the Doppler curves of these two groups. There is evidently a considerable increase in renal circulation in normal pregnancies. This is in agreement with findings described in the literature, obtained by invasive methods. On the other hand, a clear limitation of renal and uterine resistance was seen in the patients with EPH gestosis. This ties in with the well-known morphologic changes in the kidneys in cases of EPH gestosis. A larger patient sample will have to be studied to determine whether the renal vascular changes described here may represent an early sign of EPH gestosis. If this is confirmed it would make sense to include Doppler sonography of the renal vessels in routine diagnostic procedure.


Effects of the copper chelators diethyldithiocarbamate and bathocuproine sulfonate on interferon and its antiviral state.
Treatment of mouse L cells with two structurally unrelated chelators of copper ions, diethyldithiocarbamate (DDC) or bathocuproine sulfonate (BCS), completely inhibited the ability of interferon (IFN) to inhibit mengovirus growth. However, mengovirus virions were inactivated by incubation with DDC, and DDC induced a generalized inhibition of cellular RNA and protein synthesis, possibly combined with the inactivation of one or more specific enzymatic activities involved in the establishment or maintenance of the antiviral state. In contrast, BCS had no effect on either cell or virus growth. BCS combined with trace copper ions in the growth medium and the resulting complex prevented IFN from interacting properly with cellular receptors, apparently by binding noncovalently to the IFN molecules. In some cases, IFN was irreversibly inactivated, probably due to oxidation of essential cystein, tyrosine, or tryptophan residues by the (BCS)2Cu2+ complex. BCS was at least as effective as anti-IFN antibody at neutralizing cell-bound IFN, and has a number of advantages over it.