Changes in the auditory evoked potentials index by induction doses of four different intravenous anesthetics.
Many studies have investigated the electroencephalographic changes during the induction and maintenance of anesthesia. However, no comparative studies have been performed on the effects of intravenous anesthetics on the auditory evoked potentials index (AAI). The present study was performed to compare the changes in AAI caused by induction doses of thiopental, propofol, midazolam and ketamine. Eighty females, aged 30-70 years, referred for mastectomy, had anesthesia induced with thiopental 4 mg/kg, propofol 2 mg/kg, midazolam 0.1 mg/kg or ketamine 1 mg/kg (each 20 patients). The response to verbal command and the AAI were measured every minute for 5 min. The AAI decreased to less than 40 within 1 min with thiopental and propofol. The AAI increased after 3 min with thiopental, but remained low with propofol. The AAI gradually decreased to less than 40 within 4 min with midazolam, but was higher than the AAI with propofol or thiopental. The AAI increased significantly with ketamine. The AAIs at the loss of verbal command were 19 +/- 7 with thiopental, 21 +/- 8 with propofol, 31 +/- 10 with midazolam and 92 +/- 2 with ketamine. The AAI correlated with changes in hypnotic level, as measured by the response to verbal command, with induction doses of thiopental, propofol and midazolam, but not with ketamine. The AAI decreased to lower levels with propofol and thiopental than with midazolam at the induction of anesthesia.


Heterozygosity mapping by quantitative fluorescent PCR reveals an interstitial deletion in Xq26.2-q28 associated with ovarian dysfunction.
Deletions of Xq chromosome are reported for a number of familial conditions exhibiting premature ovarian failure (POF) and early menopause (EM). We describe the inheritance of an interstitial deletion of the long arm of the X chromosome associated with either POF or EM in the same family. Cytogenetic studies and heterozygosity mapping by quantitative fluorescent PCR revealed a 46,X,del(X)(q26.2-q28) karyotype in a POF female, in her EM mother, and also in her aborted fetus with severe cardiopathy. Applying a microsatellite approach, we have narrowed the extension of an identical interstitial deletion located between DXS1187 and DXS1073. These data, in line with other mapped deletions, single out the proximal Xq28 as the region most frequently involved in ovarian failure. We also propose that other factors may influence the phenotypic effect of this alteration. Indeed, skewed X inactivation has been ascertained in EM and POF to be associated with different X haplotypes. Our analysis indicates that Xq26.2-q28 deletion is responsible for gonad dysgenesis in a family with EM/POF. The dissimilar deletion penetrance may be due to epigenetic modifications of other X genes that can contribute to human reproduction, highlighting that ovarian failure should be considered as a multifactorial disease.


Morbidity and mortality following tubal ectopic pregnancies in Enugu, Nigeria.
Our objective was to determine the current incidence, clinical pattern, surgical and medical management, maternal morbidity and mortality from tubal pregnancies in Enugu, Nigeria. The records of all patients treated for tubal pregnancy at the University of Nigeria Teaching Hospital, Enugu from 1 January 1997 to 31 December 2003 were reviewed. The number of tubal ectopic pregnancies was 136, while the total number of hospital deliveries was 6,003 giving a ratio of 1:44. There were four maternal deaths due to tubal pregnancy, out of a total of 126 maternal deaths that occurred during the same period. Ectopic pregnancy was prevalent in young single women with a previous history of induced abortion and resultant pelvic infection. The most common mode of treatment is salpingectomy. Most gynaecologists are not competent in operative laparoscopy and often do not use medical management of ectopic pregnancy. However, late presentation with haemoperitoneum limits the use of conservative treatment. Maternal morbidity and mortality due to tubal pregnancy is rising in Enugu, Nigeria. Preventive efforts should aim at health education and liberal contraceptive utilisation. Provision of more sophisticated equipment and tests in the management of ectopic pregnancies may in the long term be economically viable. Currently, autotransfusion is under utilised.


Biofluid spectroscopic disease diagnostics: A review on the processes and spectral impact of drying.
The complex patterns observed from evaporated liquid drops have been examined extensively over the last 20 years. Complete understanding of drop deposition is vital in many medical processes, and one which is essential to the translation of biofluid spectroscopic disease diagnostics. The promising use of spectroscopy in disease diagnosis has been hindered by the complicated patterns left by dried biological fluids which may inhibit the clinical translation of this technology. Coffee-ring formation, cracking and gelation patterns have all been observed in biofluid drops, and with surface homogeneity being a key element to many spectroscopic techniques, experimental issues have been found to arise. A better understanding of the fundamental processes involved in a drying droplet could allow efficient progression in this research field, and ultimately benefit the population with the development of a reliable cancer diagnostic.


Malondialdehyde-Modified Low Density Lipoprotein as Oxidative-Stress Marker in Vasospastic Angina Patients.
Vasospastic angina (VSA) is caused by endothelial dysfunction and hypercontraction of vascular smooth muscle cells. Although oxidative-stress can induce endothelial dysfunction, the relationship of VSA and the oxidative-stress marker malondialdehyde-modified low density lipoprotein (MDA-LDL) remains unclear. Serum MDA-LDL was evaluated in candidate VSA patients.The subjects were 84 patients admitted to our hospital because of chest pain at rest. We stratified the patients into 3 groups; definite VSA, suspected VSA, and unlikely VSA according to a Japanese Circulation Society (JCS) guideline. The patients classified as definite VSA or suspected VSA were considered as "clinical VSA".Forty cases were classified as definite VSA, 35 as suspected VSA, and 9 as unlikely VSA. Thus, clinical VSA was the diagnosis in 75 cases. The patient characteristics showed that the average age of the patients was 60.2 years old (men, 61%). The serum MDA-LDL level of the clinical VSA group (126.3 ± 38.0 U/L) was significantly higher than the unlikely VSA group (98.7 ± 31.1 U/L). Serum MDA-LDL was positively correlated with total cholesterol (T-Chol), lowdensity lipoprotein cholesterol (LDL-C), triglycerides, and fasting blood glucose. Multivariate analysis showed that serum MDA-LDL was the most predictive marker for making a diagnosis of clinical VSA (Odds ratio 1.064, 95% confidence interval 1.014-1.145, P = 0.008). In a population with positive or borderline ECG change, the positive rate in the acetylcholine provocation test was significantly higher in the MDA-LDL higher group compared to the MDA-LDL lower group (81% versus 37%, P = 0.032).: Serum MDA-LDL might be a useful biomarker of VSA and have additional value for the diagnosis of clinical VSA.


Virus enhancement following infection with antibody-coated infectious bursal disease virus (IBDV) in chickens.
A novel concept of vaccination, employing virus-antibody complex has been reported for the control of infectious bursal disease in chickens. A comparison of virus replication, serum neutralizing antibody response and pathogenicity in chickens inoculated with the antibody coated virus, prepared by mixing virus and antibody in different ratios (1:1, 1:0.1, 1: 0.01) and virus alone without antibody, has been made. Antibody coated virus (when mixed in certain crucial ratios) replicated to a higher magnitude in the target organ, caused more severe pathogenesis but induced a primary serum neutralizing antibody response almost comparable. The results may have important implications in understanding of pathogenesis and development of control strategies against infectious bursal disease virus, specially employing immune complex vaccine.


Impact failure in two silicates revealed by ultrafast, in situ, synchrotron X-ray microscopy.
To travel safely behind screens that can protect us from stones and hail, we must understand the response of glass to impact. However, without a means to observe the mechanisms that fail different silicate architectures, engineering has relied on external sensors, post-impact examination and best-guess to glaze our vehicles. We have used single and multi-bunch, X-ray imaging to differentiate distinct phases of failure in two silicates. We identified distinct micromechanisms, operating in tandem and leading to failure in borosilicate glass and Z-cut quartz. A surface zone in the amorphous glass densifies before bulk fracture occurs and then fails the block, whilst in quartz, fast cracks, driven down cleavage planes, fails the bulk. Varying the rate at which ejecta escapes by using different indenter tip geometries controls the failed target's bulk strength. This opens the way to more physically based constitutive descriptions for the glasses allowing design of safer, composite panels by controlling the impulses felt by protective screens.


Inhibition by nitric oxide of Ca(2+) responses in rat pancreatic alpha-cells.
This study examined the effect of nitric oxide (NO) on the cytosolic free Ca(2+) concentration ([Ca(2+)](c)) of alpha-cells isolated from rat pancreatic islets. When extracellular glucose was reduced from 7 to 0 mM, about half of the alpha-cells displayed [Ca(2+)](c) oscillations. Nicardipine, a Ca(2+) channel blocker, terminated the oscillations, while thapsigargine, an inhibitor of Ca(2+)-ATPase on the endoplasmic reticulum, did not affect them, suggesting that the [Ca(2+)](c) oscillations were produced by periodic Ca(2+) influx via L-type voltage-operated Ca(2+) channels. NOC 7, an NO donor, did not cause any changes in [Ca(2+)](c) at 7 mM glucose, but reduced [Ca(2+)](c) or terminated [Ca(2+)](c) oscillations at 0 or 2.8 mM glucose. A similar inhibitory effect on [Ca(2+)](c) of alpha-cells was caused by 8-bromo-cGMP. When the [Ca(2+)](c) of alpha-cells was elevated by L-arginine in the presence of N(omega)-nitro-L-arginine, an NO synthase inhibitor, the subsequent application of NOC 7 and 8-bromo-cGMP reduced [Ca(2+)](c). As there is a direct relationship between [Ca(2+)](c) and glucagon release, these results suggest that the NO-cGMP system in rat pancreatic islets reduces glucagon release by suppressing [Ca(2+)](c) responses in alpha-cells.


Cystic fibrosis and infertility caused by congenital bilateral absence of the vas deferens and related clinical entities.
The condition of congenital bilateral absence of the vas deferens (CBAVD) is, in the majority of patients, related to defects in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CBAVD patients either are compound heterozygotes (carrying different mutations in their two CFTR genes) or carry a mutation in one of their CFTR genes and an intron 8 5T splice variant, associated with low levels of functional CFTR protein, in their second gene. The relationship between cystic fibrosis (CF) and CBAVD requires a proper clinical examination of the patient, a CFTR mutation analysis for himself and his family and genetic counselling. A mutation analysis should also be performed for the wives of CBAVD males because such couples now have the possibility of having their own genetic children but are at increased risk of having children with CF and/or CBAVD. The aetiology of some conditions of CBAVD is not related to CF, especially when CBAVD is associated with urinary tract malformations (up to 20% of cases). In couples with CBAVD not related to CF there is no increased risk of CF children, but it is not known whether they have an increased risk of having sons with CBAVD. In some of the patients with congenital unilateral absence of the vas deferens (CUAVD) the condition is also related to CF, especially in cases where there is an occlusion of the palpable vas. The CFTR gene is probably not involved in the aetiology of Young's syndrome. Follow-up studies of children born to couples where the males have CBAVD, CUAVD or Young's syndrome are mandatory and will help to better define the risk to their offspring of CF and/or of inheriting their paternal infertility condition.


Linkage between the Danish National Health Service Prescription Database, the Danish Fetal Medicine Database, and other Danish registries as a tool for the study of drug safety in pregnancy.
A linked population-based database is being created in Denmark for research on drug safety during pregnancy. It combines information from the Danish National Health Service Prescription Database (with information on all prescriptions reimbursed in Denmark since 2004), the Danish Fetal Medicine Database, the Danish National Registry of Patients, and the Medical Birth Registry. The new linked database will provide validated information on malformations diagnosed both prenatally and postnatally. The cohort from 2008 to 2014 will comprise 589,000 pregnancies with information on 424,000 pregnancies resulting in live-born children, ∼420,000 pregnancies undergoing prenatal ultrasound scans, 65,000 miscarriages, and 92,000 terminations. It will be updated yearly with information on ∼80,000 pregnancies. The cohort will enable identification of drug exposures associated with severe malformations, not only based on malformations diagnosed after birth but also including those having led to termination of pregnancy or miscarriage. Such combined data will provide a unique source of information for research on the safety of medications used during pregnancy.


Structurally Flexible Au-Cu Alloy Nanoclusters Enabling Efficient Triplet Sensitization and Photon Upconversion.
Ligand-protected noble-metal nanoclusters exhibit an innately triplet nature and have been recently recognized as emerging platforms for triplet sensitizers of photon upconversion (UC) via triplet-triplet annihilation. Herein, we report that a structurally flexible Au-Cu alloy nanocluster, [Au4Cu4(S-Adm)5(DPPM)2]+ (Au4Cu4; S-Adm = 1-adamantanethiolate, DPPM = bis(diphenylphosphino)methane), exhibited favorable sensitizer properties and superior UC performance. Contrary to the structurally rigid Au2Cu6(S-Adm)6(TPP)2 (Au2Cu6, TPP = triphenylphosphine), Au4Cu4 exhibited significantly better sensitizer characteristics, such as a near-unity quantum yield for intersystem crossing (ISC), long triplet lifetime (ca. 8 μs), and efficient triplet energy transfer (TET). The efficient ISC of Au4Cu4 was attributed to the practically negligible activation barriers during the ISC process, which was caused by the spin-orbit interaction between the two isoenergetic isomers predicted by theoretical calculations. A series of aromatic molecules with different triplet energies were used as acceptors to reveal the driving force dependence of the TET rate constant (kTET). This dependency was analyzed to evaluate the triplet energy and sensitization ability of the alloy nanoclusters. The results showed that the maximum value of kTET for Au4Cu4 was seven times larger than that for Au2Cu6, which presumably reflects the structural/electronic fluctuations of Au4Cu4 during the triplet state residence. The combination of the Au4Cu4 sensitizer and the 9,10-diphenylanthracene (DPA) annihilator/emitter achieved UC with internal quantum yields of 14% (out of 50% maximum) and extremely low threshold intensities (2-26 mWcm-2). This performance far exceeds that of Au2Cu6 and is also outstanding among the organic-inorganic hybrid nanomaterials reported so far.


Modeling food web structure and selenium biomagnification in Lake Macquarie, New South Wales, Australia, using stable carbon and nitrogen isotopes.
As a consequence of coal-fired power station operations, elevated selenium concentrations have been reported in the sediments and biota of Lake Macquarie (New South Wales, Australia). In the present study, an ecosystem-scale model has been applied to determine how selenium in a seagrass food web is processed from sediments and water through diet to predators, using stable isotopes (δ(13) C and δ(15) N) to establish the trophic position of organisms. Trophic position, habitat, and feeding zone were examined as possible factors influencing selenium bioaccumulation. Selenium concentrations ranged from 0.2 μg/g dry weight in macroalgae species to 12.9 μg/g in the carnivorous fish Gerres subfasciatus. A mean magnification factor of 1.39 per trophic level showed that selenium is biomagnifying in the seagrass food web. Habitat and feeding zone influenced selenium concentrations in invertebrates, whereas feeding zone was the only significant factor influencing selenium concentrations in fish. The sediment-water partitioning coefficient (Kd ) of 4180 showed that partitioning of selenium entering the lake to particulate organic material (POM) is occurring, and consequently availability to food webs from POM is high. Trophic transfer factors (invertebrate = 1.9; fish = 1.2) were similar to those reported for other water bodies, showing that input source is not the main determinant of the magnitude of selenium bioaccumulation in a food web, but rather the initial partitioning of selenium into bioavailable POM. Environ Toxicol Chem 2015;34:608-617. © 2014 SETAC.


[The protective effect of melatonin on auditory cortex toxicity induced by cis-platinum].
To investigate the toxic response in auditory cortex of guinea pigs caused by cis-platinum (DDP), and the protective role of melatonin in this effect. Cis-platinum and melatonin were injected peritoneally. LDH, MDA, NO in the auditory cortex were detected by spectrophotometeR. The body weight of the guinea pigs was diminished by peritoneal injection of Cis-platinum for 7 days (P < 0.01). Peritoneal injection of Cis-platinum induced the increased leakage of LDH (P < 0.05 vs injection of normal saline). This effect was reduced by injection of MT (P < 0.05). The content of MDA in the auditory cortex was also increased because of injection of Cis-platinumv for 7 days (P < 0.01) and MT reduced this effect (P < 0.05). The change of NO in the auditory cortex was not statistically significant after injection of Cis-platinum or Cis-platinum with MT. Peritoneal injection of Cis-platinum could destroy neurons in the auditory cortex. This effect could be reduced by melatonin by an anti-free radials mechanism.


Mesenchymal Stem Cell Migration during Bone Formation and Bone Diseases Therapy.
During bone modeling, remodeling, and bone fracture repair, mesenchymal stem cells (MSCs) differentiate into chondrocyte or osteoblast to comply bone formation and regeneration. As multipotent stem cells, MSCs were used to treat bone diseases during the past several decades. However, most of these implications just focused on promoting MSC differentiation. Furthermore, cell migration is also a key issue for bone formation and bone diseases treatment. Abnormal MSC migration could cause different kinds of bone diseases, including osteoporosis. Additionally, for bone disease treatment, the migration of endogenous or exogenous MSCs to bone injury sites is required. Recently, researchers have paid more and more attention to two critical points. One is how to apply MSC migration to bone disease therapy. The other is how to enhance MSC migration to improve the therapeutic efficacy of bone diseases. Some considerable outcomes showed that enhancing MSC migration might be a novel trick for reversing bone loss and other bone diseases, such as osteoporosis, fracture, and osteoarthritis (OA). Although plenty of challenges need to be conquered, application of endogenous and exogenous MSC migration and developing different strategies to improve therapeutic efficacy through enhancing MSC migration to target tissue might be the trend in the future for bone disease treatment.


International development of traditional medicine / complementary and alternative medicine research--what can Europe learn?
The aim of this study was to analyse global research and development (R&D) strategies for traditional medicine (TM) and complementary and alternative medicine (CAM) across the world to learn from previous and on-going activities. 52 representatives within CAMbrella nominated 43 key international stakeholders (individuals and organisations) and 15 of these were prioritised. Information from policy documents including mission statements, R&D strategies and R&D activities were collected in combination with personal interviews. Data were analysed using the principles of content analysis. Key stakeholders vary greatly in terms of capacity, mission and funding source (private/public). They ranged from only providing research funding to having a comprehensive R&D and communication agenda. A common shift in R&D strategy was noted; whereas 10 years ago research focused mainly on exploring efficacy and mechanisms, today the majority of stakeholders emphasise the importance of a broad spectrum of research, including methodologies exploring context, safety and comparative effectiveness. The scarce public investment in this field in Europe stands in stark contrast to the large investments found in Australia, Asia and North America. There is an emerging global trend supporting a broad research repertoire, including qualitative and comparative effectiveness research. This trend should be considered by the EU given the experience and the substantial research funding committed by the included stakeholders. To facilitate international collaborative efforts and minimise the risk of investment failure, we recommend the formation of a centralised EU CAM research centre fostering a broad CAM R&D agenda with the responsibility for implementing the relevant findings of CAMbrella.


Dynamic pay initiatives.
In the battle to manage change and deal successfully with health care reform, hospitals are looking to innovative methods to optimize compensation for their executives. Results of the 1993 Hay Hospital Compensation Survey indicate clearly that the pressures of managed care and the uncertainty--but inevitability--of reform are forcing organizations to use new tools and strategies for achieving productivity and quality goals. Another interesting survey finding: Two positions critical to the success of integrated health care systems--the head of medical affairs and the head of managed care--show significant compensation growth during the past two years.


Composite Layer-by-Layer (LBL) assembly with inorganic nanoparticles and nanowires.
New assembly techniques are required for creating advanced materials with enough structural flexibility to be tuned for specific applications, and to be practical, the techniques must be implemented at relatively low cost. Layer-by-layer (LBL) assembly is a simple, versatile, and significantly inexpensive approach by which nanocomponents of different groups can be combined to coat both macroscopically flat and non-planar (e.g., colloidal core-shell particles) surfaces. Compared with other available assembly methods, LBL assembly is simpler and more universal and allows more precise thickness control at the nanoscale. LBL can be used to combine a wide variety of species--including nanoparticles (NPs), nanosheets, and nanowires (NWs)--with polymers, thus merging the properties of each type of material. This versatility has led to recent exceptional growth in the use of LBL-generated nanocomposites. This Account will focus on the materials and biological applications of introducing inorganic nanocrystals into polymer thin films. Combining inorganic NPs and NWs with organic polymers allows researchers to manipulate the unique properties in the nanomaterial. We describe the LBL assembly technique for introducing metallic NPs into polymers in order to generate a material with combined optomechanical properties. Similarly, LBL assembly of highly luminescent semiconductor NPs like HgTe or CdTe with poly(diallyldimethylammonium chloride) (PDDA) was used to create uniform optical-quality coatings made on optical fibers and tube interiors. In addition, LBL assembly with inorganic nanosheets or clay molecules is reported for fabricating films with strong mechanical and ion transport properties, and the technique can also be employed to prepare Au/TiO(2) core/sheath NWs. The LBL approach not only will be useful for assembly of inorganic nanocrystals with various polymers but can be further applied to introduce specific functions. We discuss how the expanded use of NWs and carbon nanotubes (CNTs) in nanocomposite materials holds promise in the design of conductive films and new nanoscale devices (e.g., thin-film transistors). New photonic materials, sensors, and amplifiers can be constructed using multilayer films of NPs and can enable fabrication of hybrid devices. On the biological side, inorganic nanoshells were used as assembly tools with the goal of detecting neurotransmitters (specifically, dopamine) directly inside brain cells. In addition, the stability of different cell lines was tested for fabricating biocompatible films using LBL. NP LBL assembly was also used for homogeneous and competitive fluorescence quenching immunoassay studies for biotin and anti-biotin immunoglobulin molecules. Finally, introduction of biomolecules with inorganic NPs for creating biocompatible surfaces could also lead to new directions in the field of biomedical applications.


BRCA1 promoter hypermethylation signature for early detection of breast cancer in the Vietnamese population.
Breast cancer, a leading cause of death among women in most countries worldwide, is rapidly increasing in incidence in Vietnam. One of biomarkers is the disruption of the genetic material including epigenetic changes like DNA methylation. With the aim of finding hypermethylation at CpG islands of promoter of BRCA1 gene, belonged to the tumor suppressor gene family, as the biomarker for breast cancer in Vietnamese population, sensitive methyl specific PCR (MSP) was carried out on 115 samples including 95 breast cancer specimens and 20 normal breast tissues with other diseases which were obtained from Ho Chi Minh City Medical Hospital, Vietnam. The result indicated that the frequency of BRCA1 hypermethylation reached 82.1% in the cases (p<0.001). In addition, the DNA hypermethylation of this candidate gene increased the possibility to be breast cancer with high incidence via calculated odd ratios (p<0.05). In conclusion, hypermethylation of this candidate gene could be used as the promising biomarker application with Vietnamese breast cancer patients.


Full-length RNA structure prediction of the HIV-1 genome reveals a conserved core domain.
A distance constrained secondary structural model of the ≈10 kb RNA genome of the HIV-1 has been predicted but higher-order structures, involving long distance interactions, are currently unknown. We present the first global RNA secondary structure model for the HIV-1 genome, which integrates both comparative structure analysis and information from experimental data in a full-length prediction without distance constraints. Besides recovering known structural elements, we predict several novel structural elements that are conserved in HIV-1 evolution. Our results also indicate that the structure of the HIV-1 genome is highly variable in most regions, with a limited number of stable and conserved RNA secondary structures. Most interesting, a set of long distance interactions form a core organizing structure (COS) that organize the genome into three major structural domains. Despite overlapping protein-coding regions the COS is supported by a particular high frequency of compensatory base changes, suggesting functional importance for this element. This new structural element potentially organizes the whole genome into three major domains protruding from a conserved core structure with potential roles in replication and evolution for the virus.


Effect of vildagliptin versus glibenclamide on endothelial function and arterial stiffness in patients with type 2 diabetes and hypertension: a randomized controlled trial.
Several trials have reported that dipeptidyl peptidase-4 (DPP-4) inhibitors, used to treat type 2 diabetes (T2DM), improve endothelial function. The current study investigated the effects of vildagliptin, a DPP-4 inhibitor, compared to glibenclamide on endothelial function, arterial stiffness, and blood pressure in patients with T2DM and hypertension. Patients aged over 35 years with T2DM and hypertension, but without cardiovascular disease, were randomly allocated to treatment with vildagliptin (n = 25) or glibenclamide (n = 25). Both groups took metformin. Endothelial function was evaluated by peripheral artery tonometry (Endo-PAT 2000) to calculate the reactive hyperemia index (RHI) and arterial stiffness. Primary outcome was change in the RHI after 12 weeks of treatment. Twenty-four-hour non-invasive ambulatory blood pressure monitoring was performed using a Mobil-O-Graph® 24-h PWA monitor. Arterial stiffness was assessed using the augmentation index corrected for 75 bpm (AIx75), pulse wave velocity (PWV) and central systolic blood pressure (cSBP). There were no changes in the RHI in the vildagliptin group (before 2.35 ± 0.59; after 2.24 ± 0.60; p value = NS) or in the glibenclamide group (before 2.36 ± 0.52; after 2.34 ± 0.50; p value = NS), with no differences between groups (p value = NS). There was also no difference between vildagliptin and glibenclamide treatment in respect to AIx75 (p value = NS), cSBP (p value = NS) or PWV (p value = NS). Vildagliptin and glibenclamide similarly do not change the endothelial function and arterial stiffness after 12 weeks of treatment in diabetic and hypertensive patients without cardiovascular disease. Thus, vildagliptin has a neutral effect on vascular function. ClinicalTrials.gov: NCT02145611, registered on 11 Jun 2013.


Application of a person-centered prescription model improves pharmacotherapeutic indicators and reduces costs associated with pharmacological treatment in hospitalized older patients at the end of life.
This study sought to investigate whether applying an adapted person-centered prescription (PCP) model reduces the total regular medications in older people admitted in a subacute hospital at the end of life (EOL), improving pharmacotherapeutic indicators and reducing the expense associated with pharmacological treatment. Randomized controlled trial. The trial was registered with ClinicalTrials.gov (NCT05454644). A subacute hospital in Basque Country, Spain. Adults ≥65 years (n = 114) who were admitted to a geriatric convalescence unit and required palliative care. The adapted PCP model consisted of a systematic four-step process conducted by geriatricians and clinical pharmacists. Relative to the original model, this adapted model entails a protocol for the tools and assessments to be conducted on people identified as being at the EOL. After applying the adapted PCP model, the mean change in the number of regular drugs, STOPPFrail (Screening Tool of Older Persons' Prescriptions in Frail adults with limited life expectancy) criteria, drug burden index (DBI), drug-drug interactions, medication regimen complexity index (MRCI) and 28-days medication cost of chronic prescriptions between admission and discharge was analyzed. All patients were followed for 3 months after hospital discharge to measure the intervention's effectiveness over time on pharmacotherapeutic variables and the cost of chronic medical prescriptions. The number of regular prescribed medications at baseline was 9.0 ± 3.2 in the intervention group and 8.2 ± 3.5 in the control group. The mean change in the number of regular prescriptions at discharge was -1.74 in the intervention group and -0.07 in the control group (mean difference = 1.67 ± 0.57; p = 0.007). Applying a PCP model reduced all measured criteria compared with pre-admission (p < 0.05). At discharge, the mean change in 28-days medication cost was significantly lower in the intervention group compared with the control group (-34.91€ vs. -0.36€; p < 0.004). Applying a PCP model improves pharmacotherapeutic indicators and reduces the costs associated with pharmacological treatment in hospitalized geriatric patients at the EOL, continuing for 3 months after hospital discharge. Future studies must investigate continuity in the transition between hospital care and primary care so that these new care models are offered transversally and not in isolation.


The citalopram/5-HTP-induced head shake syndrome is correlated to 5-HT2 receptor affinity and also influenced by other transmitters.
Combination of the 5-HT-uptake inhibitor, citalopram, with 1-5-HTP induced a characteristic head shake syndrome in rats. This was blocked by a range of 5-HT antagonists, including the selective 5-HT2 antagonists, ketanserin and pirenperone and was also blocked by the alpha 1-adrenoceptor antagonists, prazosin and WB 4101, and the alpha 2-adrenoceptor agonist, clonidine. 1-5-HTP-antagonistic effect was also recorded for 26 neuroleptic drugs. Their inhibitory potencies showed close correlation to 5-HT2-receptor affinity in vitro and, slightly weaker, to alpha 1-adrenoceptor affinity. In contrast, no correlation to dopamine D-2 receptor affinity was found, indicating that the cataleptogenic and motility-inhibitory properties of neuroleptics did not unspecifically influence 1-5-HTP-induced head shakes. These were not influenced by a histaminic antagonist, muscarinic antagonist or alpha 2-adrenoceptor antagonist, but were inhibited by beta-adrenoceptor blockers, GABA agonists, a benzodiazepine and morphine. The results indicate that 1-5-HTP-induced head shakes are most sensitive to 5-HT2 antagonists, but that the syndrome is influenced by other neuronal systems. Since 5-HT2 affinity and alpha 1-adrenoceptor affinity of many compounds is found concomitantly, caution is needed to evaluate the relative importance of these properties for 1-5-HTP antagonism.


Intense blue circularly polarized luminescence from helical aromatic esters.
A new class of chiral organic molecules was synthesized with CPL properties based on helical aromatic esters. The molecules not only show blue fluorescence with high quantum yields in solution and films, but also exhibit intense CPL with large glum.


Increased bone morphogenetic protein-6 expression in mouse long bones after estrogen administration.
High-dose estrogen administration is known to induce new bone formation in mouse long bones. To study the role of regulatory proteins in this response, we examined associated changes in femoral messenger RNA (mRNA) for candidate factors. 17beta-estradiol (E2) 0.5 mg was administered to intact female mice by weekly injection, and Northern blot analysis was performed 1, 2, 4, 8, 12, and 16 days after the first injection. In contrast to other factors, an increase was observed in mRNA for bone morphogenetic protein-6 (BMP-6), which reached significance at day 8 and subsequent time-points. Estrogen-induced changes in BMP-6 protein expression were assessed by immunocytochemistry in longitudinal femoral sections. In untreated animals, BMP-6 was expressed by a significant proportion of growth plate chondrocytes and a subpopulation of bone marrow cells. In contrast, osteoblasts were consistently BMP-6 negative. From as early as 4 days after starting estrogen, clusters of slightly elongated BMP-6-positive cells were observed within the marrow cavity; the majority were close to active bone formation surfaces. Double immunolabeling studies revealed that only approximately 10% of BMP-6-positive bone marrow cells co-expressed the osteoblast transcription factor Cbfa1 suggesting that they are largely distinct from the osteoblast precursor population generated concurrently. BMP-6-positive cells expressed neither leukocyte nor erythroid markers (CD45 and TER-119, respectively), consistent with a stromal origin. We conclude that estrogen-induced osteogenesis in female mice is associated with increased levels of BMP-6 mRNA in mouse femurs, which seems to reflect the emergence of clusters of BMP-6 positive stromal cells adjacent to active bone formation surfaces. These findings raise the possibility that BMP-6 serves as a paracrine mediator of estrogen's osteogenic action in mice.


[Sociocultural reasons for the pigeon problem].
The feeding of animals as a friendly gesture is deeply rooted in man. This behaviour has a negative effect on the Street-pigeons which as a consequence suffer from overpopulation. The problem can only be solved by limiting this feeding. The pigeon-feeders are the cause of the pigeon-problem in our cities. The feeders can by their motivation be classified in various groups. Play-feeders and display-feeders can be recognised. They are more easily to be dealt with than the fanatical pigeon-friends who show a strong emotional attachment to these birds. The pigeon-problem can be overcome if this stubborn group can be taught to change his behaviour. Such a solution would be highly rewarding as great sums of money are spent to remove damages caused by the pigeons to buildings and works of art.


Predicting Incident Heart Failure in Women With Machine Learning: The Women's Health Initiative Cohort.
Heart failure (HF) is a leading cause of cardiac morbidity among women, whose risk factors differ from those in men. We used machine-learning approaches to develop risk- prediction models for incident HF in a cohort of postmenopausal women from the Women's Health Initiative (WHI). We used 2 machine-learning methods-Least Absolute Shrinkage and Selection Operator (LASSO) and Classification and Regression Trees (CART)-to perform variable selection on 1227 baseline WHI variables for the primary outcome of incident HF. These variables were then used to construct separate Cox proportional hazard models, and we compared these results, using receiver-operating characteristic (ROC) curve analysis, against a comparator model built using variables from the Atherosclerosis Risk in Communities (ARIC) HF prediction model. We analyzed 43,709 women who had 2222 incident HF events; median follow-up was 14.3 years. LASSO selected 10 predictors, and CART selected 11 predictors. The highest correlation between selected variables was 0.46. In addition to selecting well-established predictors such as age, myocardial infarction, and smoking, novel predictors included physical function, number of pregnancies, number of previous live births and age at menopause. In ROC analysis, the CART-derived model had the highest C-statistic of 0.83 (95% confidence interval [CI], 0.81-0.85), followed by LASSO 0.82 (95% CI, 0.81-0.84) and ARIC 0.73 (95% CI, 0.70-0.76). Machine-learning approaches can be used to develop HF risk-prediction models that can have better discrimination compared with an established HF risk model and may provide a basis for investigating novel HF predictors.


Insights on the formulation of herbal beverages with medicinal claims according with their antioxidant properties.
Several herbal beverages claim medicinal benefits due to their antioxidant properties. However, operational factors such as the extracted herbal component, preparation method or concentration levels, might influence their biological activity. To assess this effect, the antioxidant activity of beverages prepared with Camellia sinensis, Aspalathus linearis or Cochlospermum angolensis, used solely or mixed with different fruit, plant or algae extracts, was studied using different formulations (bags, leaves, roots, granulates, powders, liquids) and different preparation methods (infusion, solubilisation or promptly used). The DF50 (dilution factor responsible for 50% of antioxidant activity) values were calculated to compare their antioxidant activity. A linear discriminant analysis was used to categorize the assayed samples according to their antioxidant activity and bioactive molecules profiles. The results indicated that antioxidant activity and antioxidant compounds are significantly affected by formulation and preparation method, but overall the labelled antioxidant benefits were validated. Green tea showed the highest activity, but with different behaviour within each used formulation. The high DF50 values calculated for some products might be used to adjust the dietary dose or formulation, preventing also putative pro-oxidant effects. Hence, the obtained results might be useful to define the formulation of these highly consumed herbal beverages, enhancing their health effects.


[Educational curriculum and occupational status of nurses and midwives after second level degree (MNsc) at Catholic University of Rome].
Our society requires health professionals of increasingly competence, able to modulate their skills according to the needs and the requirements of the context. This survey (cross - sectional) has as primary aim to collect information on employment status of individuals who have a Master degree in Nursing and Midwifery, and as secondary objective to describe if and how the post graduation education has affected the quality and the outcomes of nursing work. A questionnaire devised for the purpose has been used. The survey was conducted from May to August 2011 on all individuals who have a Master in Nursing and Midwifery at the UCSC (from 2004-2005 to 2009-2010). Results show that in 44 cases out of 111 (= 40%) there was a change of employment status after obtaining the Master's Degree and of these 68% (30 out of 44) state that the change is definitely linked to the Post graduation education. All respondents state that the University curriculum has certainly helped to modify some professional behaviors: research utilization (93%), skills in problem solving at work (68%); greater ease to communicate the reasons underlying their organizational choices or decision making (70%); self-training abilities (63%). Within the Italian context, however it seems that those individuals are involved in a managerial progression of their career rather than in the core nursing activities despite the fact that educational programs have important subjects for Advanced Nursing Practice and Nursing Science.


Alveolar echinococcosis of the femur.
A case of alveolar echinococcosis with involvement of the femur is described. Bone involvement is extremely rare in alveolar echinococcosis. Attention is drawn to the difficulty of diagnosis, and the therapeutic possibilities are discussed.


Dyscoordinate expression of tumor necrosis factor-alpha by human blood monocytes and alveolar macrophages.
Previous studies have shown that human alveolar macrophages produce less interleukin-1 (IL-1) in response to lipopolysaccharide (LPS) than do their precursors, blood monocytes. The purpose of this study was to compare the capacities of alveolar macrophages and blood monocytes to synthesize tumor necrosis factor (TNF) in response to LPS. Alveolar macrophages were obtained by bronchoalveolar lavage of healthy nonsmoking subjects, and blood monocytes were obtained by adherence of mononuclear cells to plastic. TNF activity was measured in supernatants and cell lysates as cytotoxicity to L929 fibroblasts (uptake of neutral red at 570 nm). TNF activity of alveolar macrophages stimulated at 10(6) cells/ml with LPS (10 micrograms/ml) for 16 h was 596 +/- 367, and of blood monocytes it was 60 +/- 84 U/ml (mean +/- SD, p less than 0.005). At no concentration of LPS and at no period of stimulation did alveolar macrophages express less TNF activity than did blood monocytes. In concurrent experiments, supernatants of LPS-stimulated alveolar macrophages contained less IL-1 activity than did blood monocytes. Lysates of both cell types contained less than 20% of total TNF activity. The TNF activity of LPS-stimulated alveolar macrophages was neutralized greater than 99% by monoclonal antibody to TNF-alpha; control monoclonal antibody OKT3 had no effect. Next, alveolar macrophages and blood monocytes were biosynthetically labeled with [3H]leucine during incubation with LPS; supernatants were immunoprecipitated with anti-TNF, and precipitates were electrophoresed on polyacrylamide gels. Autoradiographs indicated that immunoreactive TNF was produced by both blood monocytes and alveolar macrophages and that the relative molecular weights were identical (17,000).(ABSTRACT TRUNCATED AT 250 WORDS)


Carbenes as Electron-Pair Donors for P⋅⋅⋅C Pnicogen Bonds.
Ab initio MP2/aug'-cc-pVTZ calculations were performed on the P⋅⋅⋅C pnicogen-bonded complexes of the singlet carbene molecules C(NH2 )2 , C(OH)2 , and cyclic C(OCH)2 [OHC] with H2 XP molecules, with X=F, Cl, NC, OH, CH3 , CN, CCH, and H. The H2 XP:C(NH2 )2 and H2 XP:C(OH)2 complexes have Cs symmetry and two different structures: one in which the symmetry plane of the complex and the local symmetry plane of the carbene are non-coplanar, and the other in which they are coplanar. The non-coplanar H2 XP:C(NH2 )2 and H2 XP:C(OH)2 complexes arise only when X is one of the more electronegative substituents. Coplanar H2 XP:C(NH2 )2 complexes form when X is one of the more electropositive substituents, whereas coplanar H2 XP:C(OH)2 complexes exist for all X. H2 XP:C(NH2 )2 and H2 XP:C(OH)2 are stabilized by covalent P-C bonds or P⋅⋅⋅C pnicogen bonds, but co-planar H2 (CH3 )P:C(OH)2 and H3 P:C(OH)2 are stabilized by O-H⋅⋅⋅P hydrogen bonds. The H2 XP:OHC complexes have non-coplanar structures that are also stabilized by P-C covalent bonds or pnicogen bonds. The H2 (CH3 )P:OHC and H3 P:OHC complexes in which the symmetry plane of the complex and the local symmetry plane of the carbene are perpendicular are stabilized by P⋅⋅⋅π bonds with P acting as the electron-pair donor to the OHC π system. The H2 XP:C(NH2 )2 , H2 XP:C(OH)2 , and H2 XP:OHC complexes are described in terms of their binding energies, charge-transfer energies, electron density properties, and equation-of-motion coupled cluster singles and doubles spin-spin coupling constants.


Two new steroidal glycosides from Cynanchum otophyllum Schneid.
Two new C21 steroidal glycosides were isolated from Cynanchum otophyllum Schneid. Their structures were elucidated as qinyangshengenin-3-O-β-d-digitoxopyranoside (1) and rostratamine-3-O-β-d-cymaropyranosyl-(1 → 4)-β-d-digitoxopyranoside (2) on the basis of chemical and spectroscopic methods, including 1D and 2D NMR experiments.


Military Occupational Outcomes in Canadian Armed Forces Personnel with and without Deployment-Related Mental Disorders.
Mental disorders are common in military organizations, and these frequently lead to functional impairments that can interfere with duties and lead to costly attrition. In Canada, the military mental health system has received heavy investment to improve occupational outcomes. We investigated military occupational outcomes of diagnosed mental disorders in a cohort of 30,513 personnel who deployed on the Afghanistan mission. Cohort members were military personnel who deployed on the Afghanistan mission from 2001 to 2008. Mental disorder diagnoses and their attribution to the Afghanistan mission were ascertained via medical records in a stratified random sample (n = 2014). Career-limiting medical conditions (that is, condition-associated restrictions that reliably lead to medically related attrition) were determined using administrative data. Outcomes were assessed from first Afghanistan-related deployment return. At 5 years of follow-up, the Kaplan-Meier estimated cumulative fraction with career-limiting medical conditions was 40.9% (95% confidence interval [CI] 35.5 to 46.4) among individuals with Afghanistan service-related mental disorders (ARMD), 23.6% (CI 15.5 to 31.8) with other mental disorders, and 11.1% (CI 8.9 to 13.3) without mental disorders. The adjusted Cox regression hazard ratios for career-limiting medical condition risk were 4.89 (CI 3.85 to 6.23) among individuals with ARMD and 2.31 (CI 1.48 to 3.60) with other mental disorders, relative to those without mental disorders. Notwithstanding the Canadian military's mental health system investments, mental disorders (particularly ARMD) still led to a high risk of adverse military occupational outcomes. Such investments have intrinsic value but may not translate into reduced medically related attrition without improvements in prevention and treatment effectiveness.


Visualizing evolution in real-time method for strain engineering.
The adaptive landscape for an industrially relevant phenotype is determined by the effects of the genetic determinants on the fitness of the microbial system. Identifying the underlying adaptive landscape for a particular phenotype of interest will greatly enhance our abilities to engineer more robust microbial strains. Visualizing evolution in real-time (VERT) is a recently developed method based on in vitro adaptive evolution that facilitates the identification of fitter mutants throughout the course of evolution. Combined with high-throughput genomic tools, VERT can greatly enhance the mapping of adaptive landscapes of industrially relevant phenotypes in microbial systems, thereby expanding our knowledge on the parameters that can be used for strain engineering.


P53/Rb inhibition induces metastatic adrenocortical carcinomas in a preclinical transgenic model.
Adrenocortical carcinoma (ACC) is a rare cancer with poor prognosis. Pan-genomic analyses identified p53/Rb and WNT/β-catenin signaling pathways as main contributors to the disease. However, isolated β-catenin constitutive activation failed to induce malignant progression in mouse adrenocortical tumors. Therefore, there still was a need for a relevant animal model to study ACC pathogenesis and to test new therapeutic approaches. Here, we have developed a transgenic mice model with adrenocortical specific expression of SV40 large T-antigen (AdTAg mice), to test the oncogenic potential of p53/Rb inhibition in the adrenal gland. All AdTAg mice develop large adrenal carcinomas that eventually metastasize to the liver and lungs, resulting in decreased overall survival. Consistent with ACC in patients, adrenal tumors in AdTAg mice autonomously produce large amounts of glucocorticoids and spontaneously activate WNT/β-catenin signaling pathway during malignant progression. We show that this activation is associated with downregulation of secreted frizzled related proteins (Sfrp) and Znrf3 that act as inhibitors of the WNT signaling. We also show that mTORC1 pathway activation is an early event during neoplasia expansion and further demonstrate that mTORC1 pathway is activated in ACC patients. Preclinical inhibition of mTORC1 activity induces a marked reduction in tumor size, associated with induction of apoptosis and inhibition of proliferation that results in normalization of corticosterone plasma levels in AdTAg mice. Altogether, these data establish AdTAg mice as the first preclinical model for metastatic ACC.


Efficacy and Safety of Catheter Ablation vs Antiarrhythmic Drugs as Initial Therapy for Management of Symptomatic Paroxysmal Atrial Fibrillation: A Meta-Analysis.
Catheter ablation is an effective treatment for atrial fibrillation (AF), primarily performed in patients who fail antiarrhythmic drugs. Whether early catheter ablation, as first-line therapy, is associated with improved clinical outcomes remains unclear. Electronic databases (PubMed, Scopus, Embase) were searched until March 28th, 2021. Randomized controlled trials (RCTs) compared catheter ablation vs antiarrhythmic drug therapy as first-line therapy were included. The primary outcome of interest was the first documented recurrence of any atrial tachyarrhythmia (symptomatic or asymptomatic; AF, atrial flutter, and atrial tachycardia). Secondary outcomes included symptomatic atrial tachyarrhythmia (AF, atrial flutter, and atrial tachycardia) and serious adverse events. Unadjusted risk ratios (RR) were calculated from dichotomous data using Mantel Haenszel (M-H) random-effects with statistical significance considered if the confidence interval (CI) excludes one and p < 0.05. A total of six RCTs with 1212 patients (Ablation n = 609; Antiarrhythmic n = 603) were included. Follow- up period ranged from 1-2 years. Patients who underwent ablation were less likely to experience any recurrent atrial tachyarrhythmia when compared to patients receiving antiarrhythmic drugs (RR 0.63; 95% CI 0.55-0.73; p < 0.00001). Symptomatic atrial tachyarrhythmia was also lower in the ablation arm (RR 0.53; 95% CI 0.32-0.87; p = 0.01). No statistically significant differences were noted for overall any type of adverse events (RR 0.93; 95% CI 0.68-1.27; p = 0.64) and cardiovascular adverse events (RR 0.90; 95% CI 0.56-1.44; p = 0.65) respectively. Catheter ablation, as first-line therapy, was associated with a significantly lower rate of tachyarrhythmia recurrence compared to conventional antiarrhythmic drugs, with a similar adverse effect risk profile. These findings support a catheter ablation strategy as first-line therapy among patients with symptomatic paroxysmal atrial fibrillation.


[A special case of 'deafness'; Landau-Kleffner syndrome].
A boy aged 5 had displayed from the age of 3 a fluctuating deficit in understanding spoken language. Audiometric testing proved his hearing to be normal. After 18 months, the parents noticed minor attacks of 'absence'. An EEG showed a normal background pattern and frequent spikes and spike waves complexes; CT-scanning of the brain revealed no abnormalities. On the basis of the acquired language disorder, the seizures and the features of the nocturnal EEG, the diagnosis the syndrome of Landau-Kleffner was made. After treatment with ethosuximide a temporary improvement of the aphasia occurred. A permanent improvement however was realized by treatment with prednisone. The boy could attend a primary school. The syndrome runs a fluctuating course; the patient may recover, but he may also undergo general mental deterioration. Antiepileptic agents only may have a brief favorable effect on the aphasia. In case of failure corticosteroids or even subpial cortical transsection are indicated.


Poly(D,L-Lactic Acid) Nanoparticle Size Reduction Increases Its Immunotoxicity.
Polylactic acid (PLA), a biodegradable and biocompatible polymer produced from renewable resources, has been widely used as a nanoparticulate platform for antigen and drug delivery. Despite generally regarded as safe, its immunotoxicological profile, when used as a polymeric nanoparticle (NP), is not well-documented. Thus, this study intends to address this gap, by evaluating the toxicity of two different sized PLA NPs (PLAA NPs and PLAB NPs), produced by two nanoprecipitation methods and extensively characterized regarding their physicochemical properties in in vitro experimental conditions. After production, PLAA NPs mean diameter (187.9 ± 36.9 nm) was superior to PLAB NPs (109.1 ± 10.4 nm). Interestingly, when in RPMI medium, both presented similar mean size (around 100 nm) and neutral zeta potential, possibly explaining the similarity between their cytotoxicity profile in PBMCs. On the other hand, in DMEM medium, PLAA NPs presented smaller mean diameter (75.3 ± 9.8 nm) when compared to PLAB NPs (161.9 ± 8.2 nm), which may explain its higher toxicity in RAW 264.7. Likewise, PLAA NPs induced a higher dose-dependent ROS production. Irrespective of size differences, none of the PLA NPs presented an inflammatory potential (NO production) or a hemolytic activity in human blood. The results herein presented suggest the hypothesis, to be tested in the future, that PLA NPs presenting a smaller sized population possess increased cytotoxicity. Furthermore, this study emphasizes the importance of interpreting results based on adequate physicochemical characterization of nanoformulations in biological medium. As observed, small differences in size triggered by the dispersion in cell culture medium can have repercussions on toxicity, and if not correctly evaluated can lead to misinterpretations, and subsequent ambiguous conclusions.


Retrospective Analysis of the Clinical Efficacy of N-Acetylcysteine in the Treatment of Hepatitis B Virus Related Acute-on-Chronic Liver Failure.
Objective: HBV-related acute-on-chronic liver failure (HBV-ACLF) has a high mortality due to severe intrahepatic cholestasis and coagulation dysfunction, thus new treatment measures are urgently needed to improve the therapeutic effect. This study aimed to observe the efficacy of N-acetylcysteine (NAC) in the treatment of HBV-ACLF. Methods: The data of patients with HBV-ACLF admitted to West China Hospital from October 2019 to August 2020 were collected retrospectively, and they were divided into treatment group and control group according to whether they had received additional NAC treatment. The improvement of biochemistry, coagulation function and disease severity score after 14 days of hospitalization were analyzed between two groups. Results: A total of 90 HBV-ACLF patients were included, including 42 patients in treatment group and 48 patients in control group. Compared with baseline, serum TBil, DBil, TBA, GGT and ALP in two groups both decreased significantly, while PTA increased significantly. Interesting, the decrease of serum TBil, DBil and TBA and the increase of PTA in treatment group were all significantly than these in control group. Additionally, more patients in treatment group than control group changed from CTP grade C to grade B. Subgroup analysis of CTP grade C patients showed that the decrease of serum TBil, DBil and TBA and the increase of PTA in treatment group were significantly than these in control group. Conclusion: The NAC treatment may help to improve intrahepatic cholestasis and coagulation dysfunction of HBV-ACLF.


Oral insulin increases small intestinal mass and disaccharidase activity in the newborn miniature pig.
Factors, such as insulin, found in human and pig colostrum and mature milk likely influence small intestinal growth and development. Although pharmacologic doses of insulin injected parenterally may accelerate small intestinal development in altricial animals such as the rodent, the effects of oral insulin on intestinal development have not been studied. In the first of two studies, we randomized 2-d-old miniature piglets to receive bottle-feedings of a swine weaning milk formula with (group F + I) or without (group F) the addition of insulin. Serum glucose, insulin, and cortisol were measured before and 1 h after the first feeding the piglets received at our facility. In the second study, piglets were randomized (groups F and F + I) and fed for 6 d, after which blood samples were obtained as in the first experiment. The piglets were then killed and the small intestine removed for analysis. We found no differences between groups in serum glucose, insulin, and cortisol at both 2 and 8 d of age, both before and after feeding. In the second experiment, small intestinal weight was greater in the F + I than in the F group. Although no differences were noted between groups in the jejunum, values were greater for group F + I versus group F for ileal mucosal weight, protein, RNA, lactase, and maltase activities. No differences were found between groups in ileal DNA or sucrase activity. We conclude that the administration of oral insulin stimulated an increase in ileal mass and disaccharidase activity in the newborn miniature pig without apparent concomitant changes in serum glucose, insulin, or cortisol.


Fire and green-tree retention in conservation of red-listed and rare deadwood-dependent beetles in Finnish boreal forests.
Habitat loss, fragmentation, and declining habitat quality have created an extinction debt in boreal forests, which could be partly reversed by deliberately improving the habitat quality in managed areas outside reserves. We studied the effects of green-tree retention and controlled burning on red-listed and rare, deadwood-dependent (saproxylic) beetles in a large-scale field experiment in eastern Finland. Our factorial study design included 24 sites dominated by Scots pine (Pinus sylvestris L.) and with three levels of green-tree retention (0, 10, and 50 m3/ha) and uncut controls. Twelve of the 24 sites were burned in 2001. We sampled beetles with 10 flight-intercept traps on each site during the years 2000-2002 (i.e., 1 pretreatment and 2 post-treatment years). A total sample of 153,449 individuals representing 1,160 beetle species yielded 2,107 specimens of 84 red-listed or rare saproxylic species. The richness of these species was higher on the burned than on the unburned sites, and higher levels of green-tree retention promoted species richness, but there were clear differences between the years. The richness of red-listed and rare saproxylic species increased in the first post-treatment year, evidently due to the treatments, continued to increase on the burned sites in the second post-treatment year, but decreased on the unburned sites. Our results showed that the living conditions of many red-listed and rare saproxylic species could be improved significantly with rather simple alterations to forest management methods. Controlled burning with high levels of green-tree retention creates resources for many saproxylic species, but increasing the levels of green-tree retention in unburned areas can also be beneficial.


Thalamic neuroaxonal dystrophy and dementia in Hodgkin's disease.
The brain of a patient with Hodgkin's disease and dementia showed numerous dystrophic axons in the thalamus. In absence of lymphomatous cellular infiltration, necrosis, hemorrhage, demyelination, neuronal loss, or infection by opportunistic organisms, the axonal dystrophy in this patient appeared to be directly related to the Hodgkin's disease itself. Moreover, dementia as a nonmetastatic complication of Hodgkin's disease may have been the result of the thalamic axonal dystrophy.


Reusable Software Usability Specifications for mHealth Applications.
One of the key factors for the adoption of mobile technologies, and in particular of mobile health applications, is usability. A usable application will be easier to use and understand by users, and will improve user's interaction with it. This paper proposes a software requirements catalog for usable mobile health applications, which can be used for the development of new applications, or the evaluation of existing ones. The catalog is based on the main identified sources in literature on usability and mobile health applications. Our catalog was organized according to the ISO/IEC/IEEE 29148:2011 standard and follows the SIREN methodology to create reusable catalogs. The applicability of the catalog was verified by the creation of an audit method, which was used to perform the evaluation of a real app, S Health, application created by Samsung Electronics Co. The usability requirements catalog, along with the audit method, identified several usability flaws on the evaluated app, which scored 83%. Some flaws were detected in the app related to the navigation pattern. Some more issues related to the startup experience, empty screens or writing style were also found. The way a user navigates through an application improves or deteriorates user's experience with the application. We proposed a reusable usability catalog and an audit method. This proposal was used to evaluate a mobile health application. An audit report was created with the usability issues identified on the evaluated application.


Predictive filtering-based fast reacquisition approach for space-borne acquisition, tracking, and pointing systems.
We propose a novel approach for recapturing targets as quickly as possible after the space-borne ATP (Acquisition, Tracking, and Pointing) system target loss in free-space laser communication. The approach uses past angular information to predict the target trajectory. An optimized finite memory filter is designed as the prediction algorithm. To obtain optimal prediction performance, the designed filter determines the filter parameters of different curve parts during offline training, and the parameters are adjusted according to the curve characteristics during predictive filtering. Simulation results indicate prediction accuracy above 0.1 degrees within 5 seconds. An experimental system was constructed in the lab to simulate the reacquisition process using a dynamic target and a real ATP system. Experimental results show that, compared with the classical orbit prediction method, this approach can effectively yield shorter acquisition times.


Acetate Promotes a Differential Energy Metabolic Response in Human HCT 116 and COLO 205 Colon Cancer Cells Impacting Cancer Cell Growth and Invasiveness.
Under dysbiosis, a gut metabolic disorder, short-chain carboxylic acids (SCCAs) are secreted to the lumen, affecting colorectal cancer (CRC) development. Butyrate and propionate act as CRC growth inhibitors, but they might also serve as carbon source. In turn, the roles of acetate as metabolic fuel and protein acetylation promoter have not been clearly elucidated. To assess whether acetate favors CRC growth through active mitochondrial catabolism, a systematic study evaluating acetate thiokinase (AcK), energy metabolism, cell proliferation, and invasiveness was performed in two CRC cell lines incubated with physiological SCCAs concentrations. In COLO 205, acetate (+glucose) increased the cell density (50%), mitochondrial protein content (3-10 times), 2-OGDH acetylation, and oxidative phosphorylation (OxPhos) flux (36%), whereas glycolysis remained unchanged vs. glucose-cultured cells; the acetate-induced OxPhos activation correlated with a high AcK activity, content, and acetylation (1.5-6-fold). In contrast, acetate showed no effect on HCT116 cell growth, OxPhos, AcK activity, protein content, and acetylation. However, a substantial increment in the HIF-1α content, HIF-1α-glycolytic protein targets (1-2.3 times), and glycolytic flux (64%) was observed. Butyrate and propionate decreased the growth of both CRC cells by impairing OxPhos flux through mitophagy and mitochondrial fragmentation activation. It is described, for the first time, the role of acetate as metabolic fuel for ATP supply in CRC COLO 205 cells to sustain proliferation, aside from its well-known role as protein epigenetic regulator. The level of AcK determined in COLO 205 cells was similar to that found in human CRC biopsies, showing its potential role as metabolic marker.


Active and intelligent packaging for food: is it the future?
This paper gives an overview of the legal consequences of a new EU framework regulation on food contact materials which includes controls on active and intelligent packaging. Recent developments in active and intelligent packaging systems are described, two examples of which aim at achieving improvements in quality and safety of food products. The first one is an on-command preservative-releasing packaging system. The second system is an intelligent concept, based on the development of a non-invasive microbial growth sensor to monitor the sterility of food products.


Shaping ability of reciprocating single-file and full-sequence rotary instrumentation systems in simulated curved canals.
The purpose of this study was to evaluate the shaping ability of three nickel-titanium systems in simulated curved canals. Sixty simulated canals were prepared to apical size 25 with Reciproc, S5, and twisted file (TF) instruments. Standardized pre and postoperative images were taken using a digital camera, were superimposed and aberrations were recorded. Material removal was measured at five points: The canal orifice, halfway to the orifice, beginning of the curve, the apex of the curve, and end-point. The data were analyzed using Kolmogorov-Smirnov, analysis of variance, and Tukey tests. The mean total width of the prepared canals in the Reciproc group was greater than the TF and S5 groups at halfway to the orifice, the beginning of the curve, the apex of the curve, and the end-point (P < 0.05). Mean absolute transportation was always <0.16 mm; however, significant differences occurred between the three systems at the orifice, halfway to the orifice, and the beginning of the curve (P < 0.05). TF created minimal absolute transportation at halfway to the orifice and the beginning of the curve, and greater absolute transportation at the orifice compared with the Reciproc and S5 instruments. However, the difference between the S5 and TF groups was not statistically significant at halfway to the orifice (P > 0.05). Under the conditions of the study, Reciproc produced widest canal shapes. TF provided more centered apical preparation and maintained the original canal shape well.


Trypanosoma cruzi: immune response and functional heart damage induced in mice by the main linear B-cell epitope of parasite ribosomal P proteins.
We report herein on the specific and autoimmune humoral response generated by the immunization of mice with the R13 synthetic peptide coupled to a carrier protein, OVA. This peptide corresponds to the C-terminal region of Trypanosoma cruzi ribosomal P1 and P2 proteins (EEEDDDMGFGLFD), a sequence that differs from the other eukariotic P consensus sequence (EESDDDMGFGLFD) only in a nonconservative amino acid substitution. The antibody response studied by ELISA revealed that all R13-immunized mice had antibodies against R13, consisting mainly of IgG1 and IgG2 isotypes, even though IgG3 and IgE isotypes were also observed. The self-reactivity of anti-R13 sera assayed by immunoblot, revealed that all sera contained IgG antibodies binding to mouse and human 38-kDa heart antigen. This antigenic band binds several immunoglobulin isotypes (IgG2 > IgG3 > IgE > IgG1). The specificity of anti-R13 antibodies analyzed by competitive inhibition of R13 ELISA using R13 and R7 (MGFGLFD) peptides revealed that the reactivity of the induced anti-P antibodies was not absorbed by R7. Therefore, the main immunogenic region of R13 for mouse would be EEEDDD, which contains the amino acid substitution. In parallel with this humoral response, both partial protection and heart damage were observed in R13-immunized mice. In fact, the R13-immunized mice showed significantly lower parasitemia and longer survival than the control animals. In addition, all R13-immunized mice showed electrocardiographic changes (bradycardia, prolonged PQ segment, and intraventricular conduction disturbances), which are typical findings in Chagas disease patients. This study represents the first definitive report in which one defined B-cell epitope, the single peptide R13 from T. cruzi, coupled to a carrier protein was able to induce specific and autoreactive antibodies as well as to generate heart functional alterations.


[European migrant crisis and reemergence of infections in Switzerland].
Current conflicts in some regions of the world give rise to massive immigration waves. Consequently, some infections that had nearly disappeared in Europe nowadays re-emerge. They are related to the epidemiology of the refugees' origin, but also to the epidemiology of the country crossed during migration. Hygiene conditions, often precarious during the journey, favor their transmission. Thus, cases of louse borne relapsing fever and diphtheria emerge in Europe and in Switzerland since 2074 whereas cutaneous Panton-Valen tine Staphylococcus aureus infection are more commonly observed nowadays.


[Isolated fracture of the medial malleolus combined with a traumatic dislocation of the peroneal tendon at the ankle joint].
A case report on an obviously rare combined injury of a fracture of the malleolus medialis and a traumatic dislocation of a peroneal tendon at the left ankle joint in a female patient of 20 years of age. The patient had had a car accident (using the safety seat belt) by colliding head-on with a tree. The ankle joint injury was confirmed by x-ray. After the usual preparations, screw osteosynthesis of the inner malleolus was performed on the fourth postoperative day. Because of persistent swelling and pain in the region of the outer malleolus despite elevation of the leg and measures to alleviate swelling, lateral revision of the ankle joint was done 14 days later, suspecting an injury of the anterior syndesmosis or of the lateral ligaments. To our surprise we discovered a traumatic dislocation of the peroneal tendon which was then surgically treated according to Kelly.


Electron radiotherapy: a study on dosimetric uncertainty using small cutouts.
This note investigated the dosimetric uncertainties due to the positional error when centring a small cutout to the machine central beam axis (CAX) in electron radiotherapy. A group of six circular cutouts with 4 cm diameter were made with their centres shifting 0, 2, 4, 6, 8 and 10 mm from the machine CAX for the 6 x 6 cm(2) applicator. The per cent depth doses, beam profiles and output factors were measured using the 4, 9 and 16 MeV clinical electron beams produced by a Varian 21 EX linear accelerator. The 2D isodose distributions in the z-x (or cross-line) and z-y (or in-line) plane were calculated by Monte Carlo simulation using the EGSnrc system. When the cutout centre was shifted away from the machine CAX for the 4 MeV beam, the d(m), R(80) and R(90) at the machine CAX had no significant change (<0.1 mm). For higher energies of 9 and 16 MeV beams, the d(m) was reduced by 0.45 and 1.63 mm per mm, between the cutout centre and the machine CAX with off-axis shift <6 mm respectively. R(80) and R(90) were reduced by more than 0.3 mm per mm off-axis shift for both energies. The isodose coverage of the in-line axis beam profile was reduced when the cutout centre was shifted away from machine CAX. It is important for oncology staff to note such dosimetric changes in the clinical electron radiotherapy, particularly when a high energy electron beam is used for small cutout. Such positional uncertainty is unavoidable in fabricating an electron cutout in the mould room.


[Two conformations of pHLA-A*2402: a supplement to Wolynes' theory].
Wolynes argued that the track of a protein's folding was directed by the tendency of lowering its energy, and thus when a local minimum of its energy was reached, a relatively stable conformation was formed. However not all of the local minimums will lead the protein to a biologically useful conformation, for those otherwise are called energy traps. Wolynes energy landscape theory and natural selection have well explained the high efficiency of protein folding in vivo, instead of being stuck in energy traps. As to whether a protein can assume different conformations with the same bioactivity, there is no clear answer yet. In this paper, two conformational states of a pHLA-A*2402 are discovered after refolding, and by studying their interactions with TCR and CD8alphaalpha, two conformations of pHLA-A*2402 are confirmed of having escaped from natural selection.


Microdomains in lipid vesicles: structure and distribution assessed by small-angle neutron scattering.
We examined the structure and distribution of microdomains in ternary multilamellar and unilamellar vesicles representing a canonical model raft mixture consisting of dioleoylphosphatidylcholine (DOPC), dipalmitoylphosphatidylcholine (DPPC), and cholesterol via contrast matched small-angle neutron scattering (SANS). The impetus of the work was to reveal the size and distribution of microdomains consistent with the form factor and intermolecular structure factor S(Q) of the scattering pattern of unilamellar and multilamellar vesicles prepared from this ternary lipid system. The data are consistent with the presence of cylindrically shaped microdomains with an average radius of approximately 15 nm assembled in a fractal-like geometry, and with corresponding modeling studies. In the multilamellar vesicle system, coupling of domains across the interlamellar water layer is observed.


Will the Needs-Based Planning of Health Human Resources Currently Undertaken in Several Countries Lead to Excess Supply and Inefficiency?
Recently, the emphasis on health human resources (HHR) planning has shifted away from a utilization-based approach toward a needs-based one in which planning is based on the projected health needs of the population. However, needs-based models that are currently in use rely on a definition of 'needs' that include only the medical circumstances of individuals and not personal preferences or other socio-economic factors. We examine whether planning based on such a narrow definition will maximize social welfare. We show that, in a publicly funded healthcare system, if the planner seeks to meet the aggregate need without taking utilization into consideration, then oversupply of HHR is likely because 'needs' do not necessarily translate into 'usage.' Our result suggests that HHR planning should track the healthcare system as access gradually improves because, even if health care is fully accessible, individuals may not fully utilize it to the degree prescribed by their medical circumstances.


Composition and Bioactivities of an (E)-β-Farnesene Chemotype of Chamomile (Matricaria chamomilla) Essential Oil from Nepal.
The essential oil of Matricaria chamomilla, collected from Nepal, was obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry. The major components in Nepalese chamomile oil were (E)-β-famesene (42.2%), α-bisabolol oxide A (22.3%), (E,E)-α-famesene (8.3%), cis-bicycloether (5.0%), α-bisabolol oxide B (4.5%), and α-bisabolone oxide A (4.0%). A cluster analysis based on the chemical compositions of 48 samples of chamomile oil reported in the literature has revealed seven chemotypes, and the oil from Nepal represents the (E)-β-farnesene chemotype. The chamomile oil was screened for antimicrobial activity against Bacillus cereus, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, and Aspergillus niger, and toxicity toward MCF-7 breast tumor cells, Artemia salina, Chaoborus plumicornis, Caenorhabditis elegans, and Drosophila melanogaster.


Enhanced anticancer efficacy of histone deacetyl inhibitor, suberoylanilide hydroxamic acid, in combination with a phosphodiesterase inhibitor, pentoxifylline, in human cancer cell lines and in-vivo tumor xenografts.
Vorinostat [suberoylanilide hydroxamic acid (SAHA)], a histone deacetylase inhibitor, shows limited clinical activity against solid tumors when used alone. The methyl xanthine drug, pentoxifylline (PENT), has been described to have antitumor properties. The aim of this study was to look for the enhanced anticancer activities of both agents when used in combination at doses lower than their respective efficacy dose when used alone. We investigated the antitumor potential of this novel combination in vitro and in vivo. The combination index was assessed for these two drugs to look for synergistic antiproliferative activity against a broad spectrum of human cancer cell lines. Consistent additive to synergistic interactions were observed in HCT116 cells when PENT was combined with SAHA at all drug tested concentrations. The combination of SAHA and PENT induces chromatin condensation and apoptosis downstream of the pan histone deacetylase inhibition and phosphodiesterase regulation, leading to subsequent cell cycle arrest at their lower tested concentrations. Further, the ability of this combination to inhibit angiogenesis, both in vitro and in vivo, was examined and a significant inhibition in tube formation in HUVEC cells and neovascularization of Matrigel plug was observed. A significant inhibition in tumor growth was observed in severe combined immunodeficient mice bearing HCT116 (colon) and PC3 (prostate) human xenografts treated with SAHA (30 mg/kg, intraperitoneal) in combination with PENT (60 mg/kg, intraperitoneal), with no loss in body weight and 100% survival. In conclusion, these findings indicate the enhanced anticancer activity of SAHA in combination with PENT both in vitro and in vivo.


Insulin action is altered in hyperthyroidism.
We have assessed insulin action in five hyperthyroid patients, pre- and post-radioactive iodine therapy using oral glucose tolerance tests, monocyte insulin binding and dose response curves generated with the euglycemic clamp technique. All patients had become euthyroid after radioactive iodine therapy with a decline in the plasma free T4 index level from 278 +/- 43 to 105 +/- 9. Fasting glucose was modestly, but significantly elevated in the thyrotoxic patients compared to when they were rendered euthyroid (p less than 0.05). Oral glucose tolerance tests showed no difference in either glucose or insulin values after the glucose load. Insulin receptor binding and affinity were similar regardless of their thyroid status. Hepatic glucose production in the basal state was elevated in the thyrotoxic patients, 61 +/- 5 mg/M2/min vs 49 +/- 3 mg/M2/min (p less than 0.05). At the lowest level of insulin infusion no difference in glucose disposal was found. At maximum insulin concentrations the glucose disposal rate was enhanced in the thyrotoxic patients, 686 +/- 19 vs 567 +/- 26 mg/M2/min (p less than 0.01). These results indicate that higher fasting glucose levels may result from increased hepatic glucose production in thyrotoxicosis, but as indicated by the oral glucose tolerance tests, this defect in insulin action is usually of minor significance. However, insulin responsiveness measured at pharmacological insulin levels is augmented in thyrotoxicosis.


The effects of proximal load on the excursion of autogenous flexor tendon grafts.
To determine the relationship between the intrinsic properties of tendon and tendon excursion in 2 types of autogenous tendon grafts, hindpaw intrasynovial and extrasynovial tendons were transferred to the lateral and medial forepaws of adult mongrel dogs (16 experimental and 16 control tendons). After each digit was marked with radiopaque markers, it was placed in a specialized jig, and weights of 25 g, 100 g, or 200 g were applied to the flexor tendons. Specialized radiographs were obtained with the digit in flexion and extension. Tendon excursion and joint rotation were calculated. There were no statistically significant differences between experimental groups for tendon excursion or for joint angular rotation (p > .05). For intrasynovial tendon grafts, the angular rotation per millimeter tendon excursion was 10.9 degrees +/- 2.4 degrees/mm, 9.4 degrees +/- 1.2 degrees/mm, and 9.0 degrees +/- 1.4 degrees/mm with 25-g, 100-g, and 200-g loads, respectively. Comparisons between experimental groups revealed that a statistically significant difference could not be determined (p > .05). With varying proximal loads, both intrasynovial and extrasynovial grafts showed similar amounts of tendon excursion. Variations in proximal load did not significantly influence the amount of excursion within the range of loads tested. Based on these data, it appears that the difference in repair potential for these 2 types of tendon grafts is not related to a differential in the amount of tendon graft excursion following transfer to the synovial space.


Ovarian hemangioma with stromal luteinization and HCG-producing mononucleate and multinucleate cells of uncertain histogenesis: a rare co-existence with therapeutic dilemma.
A 21 year old female presented with amenorrhea, hirsutism and change in voice along with an elevated serum β-HCG (human chorionic gonadotrophin) level and normal CA-125 level. Laparotomy revealed an enlarged right ovary measuring 6×5×1 cms with presence of an ovarian hemangioma along with stromal luteinization and HCG producing mononucleate as well as multinucleate cells of uncertain histogenesis on histopathological examination. Immunohistochemistry for inhibin and calretinin were positive in the luteinized component whereas β-HCG and Ki-67 were positive in the multinucleate cell component. The diagnostic rarity and therapeutic dilemma of such a rare mixed tumor within a single ovary has proven to be an exceptional case and an excellent investigative opportunity.


Plant-driven niche differentiation of ammonia-oxidizing bacteria and archaea in global drylands.
Under controlled laboratory conditions, high and low ammonium availability are known to favor soil ammonia-oxidizing bacteria (AOB) and archaea (AOA) communities, respectively. However, whether this niche segregation is maintained under field conditions in terrestrial ecosystems remains unresolved, particularly at the global scale. We hypothesized that perennial vegetation might favor AOB vs. AOA communities compared with adjacent open areas devoid of perennial vegetation (i.e., bare soil) via several mechanisms, including increasing the amount of ammonium in soil. To test this niche-differentiation hypothesis, we conducted a global field survey including 80 drylands from 6 continents. Data supported our hypothesis, as soils collected under plant canopies had higher levels of ammonium, as well as higher richness (number of terminal restriction fragments; T-RFs) and abundance (qPCR amoA genes) of AOB, and lower richness and abundance of AOA, than those collected in open areas located between plant canopies. Some of the reported associations between plant canopies and AOA and AOB communities can be a consequence of the higher organic matter and available N contents found under plant canopies. Other aspects of soils associated with vegetation including shading and microclimatic conditions might also help explain our results. Our findings provide strong evidence for niche differentiation between AOA and AOB communities in drylands worldwide, advancing our understanding of their ecology and biogeography at the global scale.


First case report of Pacinian corpuscle hyperplasia following complex regional pain syndrome.
Pacinian disorders are exceedingly rare, and the exact pathogenesis is still unknown. The most common symptoms are pain, sensory changes, and a visible or palpable mass, and diagnosis is usually made by pathological examination after the excision of the painful nodule. In this case report, we present the case of a 49-year-old male with Pacinian corpuscle hyperplasia located on the metacarpophalangeal joint, emerging at the same hand of the patient two years after the treatment due to complex regional pain syndrome (CRPS). To the best of our knowledge, this is the first case report revealing the association of CRPS with hyperplasia of Pacinian corpuscles.


Investigation of parabens in commercial cosmetics for children in Beijing, China.
Parabens are one of the most common preservatives in cosmetics. Because allergenicity and cytotoxicity potential values are major aspects of preservative safety and parabens are xenoestrogens, safety levels of parabens have been restricted in "Hygienic Standard for Cosmetics" (2007 edition) by the Ministry of Public Health of China, and a high-performance liquid chromatography (HPLC) for the simultaneous determination of parabens is recommended. To investigate whether the commonly used parabens in children's cosmetics were at a safety level, 105 cosmetics for children were randomly purchased from the local market in Beijing and analyzed by the proposed HPLC method. The detection rate of methylparaben was the highest and the next was propylparaben. Among the 105 samples, two or more kinds of parabens were detected in 72 samples with concentrations ranging from 0.02% to 0.75%; 18 samples contained one kind of paraben with concentrations ranging from 0.002% to 0.06%. In this study, the contents of parabens in the 105 samples were all below the restricted levels.


Wilson's disease in young children from northern India.
Though Wilson's disease is not uncommon, there is paucity of reported cases from northern India. Out of 500 new cases registered during 1979-1986 in Chandigarh, nine were diagnosed to have Wilson's disease. Six children presented with a primary liver disease, two with neurological manifestations while one was an asymptomatic sib. All children with hepatic presentation were aged 8 yr or less (mean 6.5 yr). Kayser-Fleischer rings were demonstrable in 8 patients. The disease affects Indian children at a younger age and the diagnosis should be considered in those presenting with an typical hepatic/neurological disorder, Early diagnosis and treatment is mandatory for appropriate management.


Role of Sentinel Lymph Node Drainage Mapping for Localization of Contralateral Lymph Node Metastasis in Locally Advanced Oral Squamous Cell Carcinoma - A Prospective Pilot Study.
Sentinel lymph node biopsy (SLNB) has become the standard of care for nodal staging in early-stage oral squamous cell carcinoma (OSCC) as an alternative to elective neck dissection. However, the role of sentinel lymph node (SLN) and lymphatic drainage mapping with image-guided surgery has not been studied in locally advanced OSCC. Therefore, this study was undertaken to evaluate the role of lymphatic drainage mapping in the identification of contralateral cervical lymph node metastasis in locally advanced OSCC (Stage III-IVb). We have prospectively analyzed treatment-naïve patients of locally advanced, lateralized OSCC (n = 20). All patients underwent SLN imaging using peritumoral injection 0.5-1.0 mCi of 99 mTc-Sulfur colloid (Filtered) and intraoperative identification of contralateral neck nodes using a handheld gamma probe (Crystal Photonics). A total of 20 patients (18 males and 2 females) with a median age of 52.5 (33-70 years) were included. Ipsilateral SLN was localized in 18 (90%) patients. Bilateral cervical nodes were visualized only in 7 (35%) patients on lymphoscintigraphy (LSG). Out of the seven patients, 5 patients underwent bilateral neck dissection and 2 patients had unilateral neck dissection with LSG-guided exploration of contralateral cervical node and intraoperative frozen section examination. Six out of these seven patients had one or other risk factor for contralateral metastasis (patients had either primary in the tongue, involvement of floor of mouth, or tumor thickness >3.75 mm). On postoperative HPE, only 1/20 (5%) patient showed metastasis in the contralateral cervical lymph node. Correct identification of metastatic disease in contralateral neck directly influences clinical management, as it can reduce contralateral neck failure rate and limit the morbidity associated with unnecessary contralateral neck dissection, and it is also crucial in radiotherapy planning in locally advanced OSCC. In the current study, lymphatic drainage mapping showed a metastatic rate of 5% in the contralateral neck nodes in locally advanced, lateralized OSCC. However, the role of SLNB and lymphatic drainage mapping in this subgroup of OSCC needs to be studied in larger population to validate these findings.


Microfibrillar-associated protein 4 in serum is associated with asthma in Danish adolescents and young adults.
Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein belonging to the fibrinogen-related protein superfamily, which plays multifaceted roles in innate immunity and normal endothelial function. It has been proposed that MFAP4 promotes the development of asthma in vivo and proasthmatic pathways of bronchial smooth muscle cells in vitro. The aim of this study was to investigate the significance of serum MFAP4 in adolescents and young adolescents with persistent asthma. Prospective, observational study including adolescents and young adults (age 11-27 years) previously diagnosed with asthma during childhood 2003 to 2005 (0-15 years) at the four pediatric outpatient clinics in the Region of Southern Denmark (n = 449). Healthy controls were recruited at follow-up (n = 314). Detection of serum MFAP4 was performed by AlphaLISA technique. Current asthma was associated to a 14% higher mean level of serum MFAP4 compared with controls (expβ 1.14, 95% confidence intervals [CI], 1.05-1.23) and a 6% higher mean level compared with subjects with no current asthma (expβ 1.06, 95% CI, 0.99-1.13). No association was found at follow-up between serum MFAP4 and self-reported atopic symptoms (other than asthma), Asthma Control Test-score, fractional exhaled nitric oxide (FeNO), nor to flow rate at 1 second, forced vital capacity, and forced expiratory flow 25% to 75%, response to short-acting beta 2 agonist or mannitol. We found a significantly higher mean level of serum MFAP4 in adolescent and young adults with mild to moderate asthma compared with healthy controls but no association to FeNO and lung function nor to the response to short-acting beta 2 agonist or mannitol. The result supports the hypothesis that MFAP4 plays a role in the pathogenesis of asthma although the marker did not demonstrate any obvious potential as an asthma biomarker in adolescents and young adults with asthma. To understand the possible proasthmatic functions of MFAP4, further investigation in specific asthma phenotypes and the underlying molecular mechanisms is warranted.


Discovery of Inactive Conformation-Selective Kinase Inhibitors by Utilizing Cascade Assays.
Achieving selectivity across the human kinome is a major hurdle in kinase inhibitor drug discovery. Targeting inactive (vs active) kinase conformations offers advantages in achieving selectivity because of their more diversified structures. Discovery of inactive conformation-selective inhibitors, however, has been hampered partly by the lack of general assay methods. Herein, we show that such inhibitors can be discovered by utilizing kinase cascade assays. This type of assay is initiated with the target kinase in its unphosphorylated, inactive conformation, which is activated during the assay. Inactive conformation-selective inhibitors stabilize the inactive kinase, block activation, and yield reduced kinase activity. We investigate the properties of the assay by mathematical modeling, as well as by proof-of-concept experiments using the BRAF-MEK1 cascade. This study demonstrates effective identification of inactive conformation-selective inhibitors by cascade assays, reveals key factors that impact results, and provides guidelines for successful cascade assay development.


The controversy surrounding bone morphogenetic proteins in the spine: a review of current research.
Bone morphogenetic proteins have been in use in spinal surgery since 2002. These proteins are members of the TGF-beta superfamily and guide mesenchymal stem cells to differentiate into osteoblasts to form bone in targeted tissues. Since the first commercial BMP became available in 2002, a host of research has supported BMPs and they have been rapidly incorporated in spinal surgeries in the United States. However, recent controversy has arisen surrounding the ethical conduct of the research supporting the use of BMPs. Yale University Open Data Access (YODA) recently teamed up with Medtronic to offer a meta-analysis of the effectiveness of BMPs in spinal surgery. This review focuses on the history of BMPs and examines the YODA research to guide spine surgeons in their use of BMP in spinal surgery.


Separation and cultivation of laryngeal carcinoma-associated fibroblasts and biological influence on a laryngeal carcinoma cell line.
Carcinoma-associated fibroblasts (CAFs) can influence the biological characteristics of a laryngeal carcinoma cell line. These results could lay the foundation for further studies on the role of CAFs in the laryngeal tumor-host microenvironment. CAFs are important contributors to the microenvironment in determining the fate of tumors. The aim of this study was to separate, culture, and identify laryngeal CAFs and investigate their biological influence on the laryngeal carcinoma cell line. The primary CAFs and normal fibroblasts (NFs) of the larynx were obtained by tissue culture. The cells were verified according to immunohistochemical and immunofluorescence staining of certain proteins. Conditioned medium (CM) from CAFs and NFs was obtained. Functional assays were performed to test the influence of each CM on laryngeal carcinoma cell lines. Third-passage purified laryngeal CAFs and NFs were successfully attained. The CAFs showed positive staining for vimentin, α-smooth muscle actin (α-SMA), and fibroblast activation protein (FAP). The migration ability of the CAFs increased significantly compared with that of NFs (p < 0.05). CM from CAFs (compared with CM from NFs) stimulated proliferation, migration, and invasion to a greater extent.


Ribbing disease.
Ribbing disease is a rare sclerosing dysplasia that involves long tubular bones, especially the tibia and femur. It occurs after puberty and is reported to be more common in women. In this article we describe how Ribbing disease can be differentiated from diseases like Engelmann-Camurati disease, van Buchem disease, Erdheim-Chester disease, osteoid osteoma, chronic osteomyelitis, stress fracture, etc.


Influence of Chronic Periodontitis on the Long-Term Mortality and Cardiovascular Events in Kidney Transplant Recipients.
Chronic periodontitis (CP) is associated with cardiovascular disease and mortality in different populations. The aim of this study was to examine an association of CP with hard endpoints in patients after kidney transplantation during a 15-year follow-up period. Study group consist of 117 patients (77M/40F, median age 44 years) divided into two subgroups: those with initially advanced CP (CPITN 3-4) and those with no or moderate CP (CPITN 0-2). All cardiovascular events, graft losses, and re-transplantations were recorded. All deaths were noted and verified, including those occurred after the return to dialysis therapy, the causes of death were identified. Cox regression with Firth's penalized maximum likelihood models were used for data analysis. During the observation period, 49 deaths occurred. Advanced CP (n = 35) was not associated with overall mortality but was associated with increased risk of death with functioning graft (DWFG) [HR 3.54 (1.20-10.45); p < 0.05]. Risk of graft loss was not associated with CP status. In conclusion, an advanced CP was independently associated with increased risk of DWFG, but not all-cause or cardiovascular mortality after renal transplantation.