Comparison of methods for generating planar DNA-modified surfaces for hybridization studies.
The surface conformation and accessibility of oligonucleotides within arrays are two key parameters that affect the utility of immobilized nucleic acids in sensor technologies. In this work, a novel combination of analytical techniques was used to compare two methods for DNA immobilization on glass. The aim of the study was to identify a method that generated a high surface density of hybridization-accessible oligonucleotides in a true planar monolayer. The first method based on direct coupling of silanized DNA to the glass surface showed a high immobilization density of 0.013 molecules/nm2 but low surface accessibility, as shown by the hybridization measurements (< or =15%). The second method, based on the biotin-streptavidin interaction, generated a high immobilization density (0.02 molecules/nm2) and high surface accessibility (90%). Atomic force microscopy and X-ray photoelectron spectroscopy indicated that both methods achieved uniform surfaces. Using the biotin-streptavidin system, the intermolecular distance between the hybridized molecules could be tightly controlled by titrating biotinylated complementary and noncomplementary oligonucleotides.


Novel model to study virulence determinants of Escherichia coli K1.
It is shown here for the first time that locusts can be used as a model to study Escherichia coli K1 pathogenesis. E. coli K-12 strain HB101 has very low pathogenicity to locusts and does not invade the locust brain, whereas the injection of 2 x 10(6) E. coli K1 strain RS218 (O18:K1:H7) kills almost 100% of locusts within 72 h and invades the brain within 24 h of injection. Both mortality and invasion of the brain in locusts after injection of E. coli K1 require at least two of the known virulence determinants shown for mammals. Thus, deletion mutants that lack outer membrane protein A or cytotoxic necrotizing factor 1 have reduced abilities to kill locusts and to invade the locust brain compared to the parent E. coli K1. Interestingly, deletion mutants lacking FimH or the NeuDB gene cluster are still able to cause high mortality. It is argued that the likely existence of additional virulence determinants can be investigated in vivo by using this insect system.


Abdominal aortic aneurysms before and after endograft implantation: evaluation by computed tomography.
The evaluation of patients with abdominal aortic aneurysms for endograft candidacy and their follow-up after treatment are heavily dependent on radiologic imaging. Factors never considered during conventional open repair have become crucial to patient selection and procedural success, and the new and developing nature of the field of endovascular repair necessitates close surveillance of these devices after deployment. Computed tomography (CT) has emerged as the single most effective imaging tool for the preprocedural assessment and subsequent follow-up of these patients. This article outlines the technical parameters for obtaining pre- and postoperative CT examinations in endograft patients and discusses the important imaging findings.


White matter microstructures underlying mathematical abilities in children.
The role of gray matter function and structure in mathematical cognition has been well researched. Comparatively little is known about white matter microstructures associated with mathematical abilities. Diffusion tensor imaging data from 13 children (7-9 years) and two measures of their mathematical competence were collected. Relationships between children's mathematical competence and fractional anisotropy were found in two left hemisphere white matter regions. Although the superior corona radiata was found to be associated with both numerical operations and mathematical reasoning, the inferior longitudinal fasciculus was correlated with numerical operations specifically. These findings suggest a role for microstructure in left white matter tracts for the development of mathematical skills. Moreover, the findings point to the involvement of different white matter tracts for numerical operations and mathematical reasoning.


The association of low serum salivary and pancreatic amylases with the increased use of lipids as an energy source in non-obese healthy women.
It is unknown whether low serum levels of salivary and pancreatic amylases are associated with the high combustion of carbohydrates or lipids for energy. Elevated blood ketones and a low respiratory quotient (RQ) can reflect the preferential combustion of lipids relative to carbohydrates. Therefore, using the data from our previous study, we investigated if low levels of serum amylases were associated with a high serum ketone level and low RQ in 60 healthy non-obese young women aged 20-39 years old. Serum ketones [3-hydroxybutyric acid (3-HBA) and acetoacetic acid (AA)] were inversely correlated with RQs, but not body mass index (BMI) or glycated haemoglobin (HbA1c) levels. Logistic regression analysis showed that high levels of serum ketones (3-HBA ≥ 24 μmol/L and AA ≥ 17 μmol/L) and a low RQ (< 0.766) were significantly associated with low serum salivary (< 60 U/L) and pancreatic (< 29 U/L) amylase levels, respectively. These associations were not altered by further adjustments for age, BMI, HbA1c, and estimated glomerular filtration rate. These results confirm the high combustion of lipids for energy in individuals with low serum amylase levels, suggesting a close relationship between circulating amylases and internal energy production.


Does the sagittal spinal profile differ between the elderly Chinese populations with and without lumbar disc herniation?
To explore the characteristics of the sagittal spinopelvic profile in the elderly Chinese population with lumbar disc herniation (LDH) and to evaluate its influence on the severity, location and number of disc degeneration. A retrospective analysis was conducted on 212 elderly Chinese patients with LDH and 213 asymptomatic volunteers with matched age and sex. Sagittal spinopelvic parameters were measured on the full-length X-ray and the sagittal profiles were determined according to the Roussouly classification. The severity, location and number of lumbar disc degeneration were evaluated from the L12 to L5S1 discs on the MRI images. There were no significant differences in BMI between the two groups. Patients with LDH were found to have significantly smaller TK, LL, and SS than those in the asymptomatic population (P < 0.05), while contradicting observations were obtained of PT and TPA (P < 0.05). In the LDH group, Roussouly type 1 and type 2 (50.4% and 28.7%, respectively) were predominant and the proportion of type 1 in the elderly LDH population was further increased compared to the younger LDH population. LDH population with Roussouly type 1 and 2 showed more caudal herniated locations and fewer herniated numbers than those with type 3 and 4. The sagittal spinopelvic profile was significantly different between the elderly Chinese population with and without LDH. There were significant differences in the Roussouly distribution between the elderly and the younger groups and different Roussouly types have different effects on the lumbar disc degeneration patterns.


Impact of age on the relationships of brown adipose tissue with sex and adiposity in humans.
Brown adipose tissue (BAT) regulates energy homeostasis and fat mass in mammals and newborns and, most likely, in adult humans. Because BAT activity and BAT mass decline with age in humans, the impact of BAT on adiposity may decrease with aging. In the present study we addressed this hypothesis and further investigated the effect of age on the sex differences in BAT activity and BAT mass. Data from 260 subjects (98 with BAT and 162 study date-matched control subjects) who underwent (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) under thermoneutral conditions were analyzed. BAT activity and BAT mass were determined in the upper body. BAT activity and BAT mass were higher in female (1.59 +/- 0.10 and 32 +/- 5 g vs. 1.02 +/- 0.10 and 18 +/- 4 g, both P < or = 0.0006) than in male subjects. In multivariate analyses, sex (P < 0.0001), age (P < 0.0001), and BMI (P = 0.0018) were associated independently with BAT activity. Interestingly, only in male subjects was there an interaction between BMI and age in determining BAT activity (P = 0.008) and BAT mass (P = 0.0002); BMI decreased with increasing BAT activity and BAT mass in the lowest age tertile (Spearman rank correlation coefficient r(s) = -0.38, P = 0.015 and r(s) = -0.37, P = 0.017, respectively), not in the higher age tertiles. Furthermore, BAT activity and mass differed between female and male subjects only in the upper two age tertiles (all P < or = 0.09). Our data corroborate that, in general, BAT activity and BAT mass are elevated in female subjects and in younger people. Importantly, we provide novel evidence that the impact of BAT activity and BAT mass on adiposity appears to decline with aging only in male subjects. Furthermore, while BAT activity and BAT mass only moderately decline with increasing age in female subjects, a much stronger effect is found in male subjects.


Dephosphorylation of the lipid A moiety of Escherichia coli lipopolysaccharide by mouse macrophages.
An Escherichia coli deep rough lipopolysaccharide (LPS), biosynthetically labeled with 32PO4 and [3H]glucosamine, was used to study dephosphorylation of the lipid A moiety by murine macrophages. Over a 48-h incubation period, the macrophages removed approximately two-thirds of the 32P from [3H32P]LPS that was added to the culture medium. The LPS-derived phosphate was incorporated into cell components (e.g., phospholipids), as well as released from the cells. Cell lysates were also able to remove phosphate from [3H32P]LPS. The phosphatase activity was optimal at acidic pH and was greatly reduced by 10 mM sodium fluoride or heating at 80 degrees C. There was no evident difference in the LPS-dephosphorylating ability of macrophages from LPS-responsive and -hyporesponsive mice. The results indicate that murine macrophages dephosphorylate the lipid A moiety of deep rough E. coli LPS and raise the possibility that enzymatic dephosphorylation may modify LPS bioactivity.


Connexin32 deficiency exacerbates carbon tetrachloride-induced hepatocellular injury and liver fibrosis in mice.
Liver fibrosis results from the perpetuation of the normal wound healing response to several types of injury. Despite the wealth of knowledge regarding the involvement of intracellular and extracellular signaling pathways in liver fibrogenesis, information about the role of intercellular communication mediated by gap junctions is scarce. In this study, liver fibrosis was chemically induced by carbon tetrachloride in mice lacking connexin32, the major liver gap junction constituent. The manifestation of liver fibrosis was evaluated based on a series of read-outs, including collagen morphometric and mRNA analysis, oxidative stress, apoptotic, proliferative and inflammatory markers. More pronounced liver damage and enhanced collagen deposition were observed in connexin32 knockout mice compared to wild-type animals in experimentally triggered induced liver fibrosis. No differences between both groups were noticed in apoptotic signaling nor in inflammation markers. However, connexin32 deficient mice displayed decreased catalase activity and increased malondialdehyde levels. These findings could suggest that connexin32-based signaling mediates tissue resistance against liver damage by the modulation of the antioxidant capacity. In turn, this could point to a role for connexin32 signaling as a therapeutic target in the treatment of liver fibrosis.


Enhanced Tendon-to-Bone Healing of Chronic Rotator Cuff Tears by Bone Marrow Aspirate Concentrate in a Rabbit Model.
To evaluate the influence of bone marrow aspirate concentrate (BMAC) on tendon-to-bone healing in a rabbit rotator cuff model and to characterize the composition of growth factors in BMAC. In this in vivo study, 40 rabbits were allocated into five groups: control (C), repair + saline (RS), repair + platelet-rich plasma (PRP; RP), repair + BMAC (RB) and repair + PRP + BMAC (RPB). A tear model was created by supraspinatus tendon transection at the footprint. Six weeks after transection, the torn tendon was repaired along with BMAC or PRP administration. Six weeks after repair, shoulder samples were harvested for biomechanical and histological testing. Ten rabbits were used for processing PRP and BMAC, followed by analysis of blood cell composition and the levels of growth factors in vitro. The ultimate load-to-failure was significantly higher in RPB group compared to RS group (p = 0.025). BMAC-treated groups showed higher values of biomechanical properties than RS group. The histology of BMAC-treated samples showed better collagen fiber continuity and orientation than RS group. BMAC contained significantly higher levels of the several growth factors than PRP. Locally administered BMAC enhanced tendon-to-bone healing and has potential for clinical applications.


Thermally Stable Metallic Nanoparticles Prepared via Core-Cross-linked Block Copolymer Micellar Nanoreactors.
Thermally stable metallic nanoparticles (MNPs) are highly desirable for the melt processing of polymer nanocomposites. However, due to the high surface energy penalty and decreased melting temperature, MNPs are easy to agglomerate and lose their unique properties if there is no protection or confinement layer. In this work, we report a facile and efficient way to synthesize thermally stable MNPs using core-cross-linked polystyrene-b-poly(4-vinylpyridine) (PS-b-P4VP) reverse micelles as nanoreactors. From infrared results, gold, silver, and palladium ions exhibited distinctive coordination to the 4VP groups with varying chelation strengths. Compared to the non-cross-linked micelles, 1,4-dibromobutane (DBB)-cross-linking of the P4VP cores provided several advantages. First, it prevented severe swelling of the P4VP cores caused by the reducing agents and subsequent merger of swollen micelles. Second, the quaternized P4VP with hydrophilicity enhanced the uptake speed of precursor metal ions into the cores. Third, the cross-linked cores greatly stabilized the MNPs against the high-temperature environment (e.g., 110 °C for 40 h in toluene). In addition, the solubility of the reducing agents also played an important role. Anhydrous hydrazine could swell the P4VP cores and concentric core-shell particle morphology was obtained. On the contrary, triethylsilane could not swell the P4VP cores and thus eccentric core-shell particle morphology was observed. Only the concentric core-shell MNPs exhibited good thermal stability, whereas the eccentric core-shell MNPs did not. This work suggested that these thermally stable MNPs could be good candidates for the melt processing of functional polymer nanocomposites.


Ultrastructural localization of relaxin immunoreactivity in corpora lutea of pregnant rats.
Relaxin was localized in cells of corpora lutea of pregnant rats at the ultrastructural level using a highly specific antirat relaxin serum and the unlabeled peroxidase-antiperoxidase technique. Electron-dense, membrane-bound granules (maximum diameter, 270 nm), which are present in luteal cells during the last third of gestation, were the only inclusions that were immunochemically stained. The number of granules observed in the luteal cell cytoplasm varied from cell to cell within a particular section. Furthermore, in the granule-rich luteal cells, the granules appeared in clusters. This study establishes that these electron-dense granules represent the subcellular sites of relaxin localization within luteal cells of pregnant rats.


Health-related quality of life does not predict mortality in idiopathic pulmonary fibrosis.
Although health-related quality of life (HRQL) has recently been considered to be an important outcome in clinical trials of idiopathic pulmonary fibrosis (IPF), its relationship with survival is unknown. To determine the prognostic significance of HRQL scores in IPF assessed with the SGRQ. Eighty-seven consecutive patients with IPF, who had undergone evaluations and completed the St. George's Respiratory Questionnaire (SGRQ) at diagnosis were included in this study, as is the general practice. Cox proportional hazards analyses were performed to examine the relationship between HRQL scores and survival. The mean observation period was 44.2 +/- 29.6 mo, in the course of which 54 patients (62.0%) died. Univariate analysis revealed that the activity scores in the SGRQ(HR: 1.016, 95% CI: 1.004-1.029, P = 0.01) were significantly predictive of survival, although the symptoms, impacts, and total scores were not significantly related to mortality from all causes. However, multivariate analysis revealed that only the forced vital capacity percent predicted was a significant predictor of survival, and that the activity score in the SGRQwas not significantly related to mortality. There was no significant relationship between HRQL evaluated with the SGRQ and the subsequent mortality in IPF. The present negative result might suggest that HRQL is measuring an aspect other than one from physiological and functional impairment or disability.


Injuries in commercial whitewater rafting on the New and Gauley rivers of West Virginia.
To describe the rates, patterns, and likelihood of injuries in commercial whitewater rafting on the New and Gauley rivers, West Virginia. Standardized injury report forms developed by the West Virginia Whitewater Commission were reviewed for years 2005-2010 to provide a statistical account of injuries reported by licensed commercial rafting outfitters operating on the New and Gauley rivers. Overall, musculoskeletal injuries (sprains/strains, 21.1%; dislocations, 13.8%; fractures, 12.2%) comprised the majority (47.4%) of incidents followed by injuries to soft tissue (lacerations, 29.0%; abrasions, 13.3%; contusions, 2.3%). Almost one half (44.3%) of injuries were to the head, neck, and shoulders followed by the lower extremities (foot/ankle/leg/knee/hip, 33.9%) and upper extremities (hand/wrist/arm, 14.3%). Data analyzed using the Somers' D statistic revealed the likelihood of an injury occurring inside the raft is P = .55, and P = .39 when passengers are ejected from the raft into the river. The most likely injuries to occur to passengers are a laceration (P = .51) or a sprain (P = .20). The main probabilities for the risks of injuries were found to be to the head (P = .24), shoulder (P = .16), and face (P = .13) of the passenger. By knowing what injuries are common, their likelihood of occurrence, and the settings in which they happen, commercial outfitters can initiate practices to reduce injury rates.


Modeling the temporal dynamics of distinctive feature landmark detectors for speech recognition.
This paper elaborates on a computational model for speech recognition that is inspired by several interrelated strands of research in phonology, acoustic phonetics, speech perception, and neuroscience. The goals are twofold: (i) to explore frameworks for recognition that may provide a viable alternative to the current hidden Markov model (HMM) based speech recognition systems and (ii) to provide a computational platform that will facilitate engaging, quantifying, and testing various theories in the scientific traditions in phonetics, psychology, and neuroscience. This motivation leads to an approach that constructs a hierarchically structured point process representation based on distinctive feature landmark detectors and probabilistically integrates the firing patterns of these detectors to decode a phonological sequence. The accuracy of a broad class recognizer based on this framework is competitive with equivalent HMM-based systems. Various avenues for future development of the presented methodology are outlined.


When incentives and professionalism collide.
As Jin Ma and colleagues observe, an unfettered market approach in China has reduced access to care, increased patients' financial burden, and reduced emphasis on prevention and may have caused declines in quality and outcomes. A major driving force was that perverse incentives altered physicians' behavior toward self-interest at the expense of patients, even where professional ethics dictated otherwise. Other nations, including India, are grappling with the profit motive and its consequences. Chinese leaders are attempting to deal with these problems by expanding public investment and reducing perverse incentives. However, profit motives remain a powerful, potentially offsetting feature of a reformed system.


Preservation of clonal heterogeneity of the Pneumocystis carinii-specific CD4 T cell repertoire in HIV infected, asymptomatic individuals.
The loss of CD4 lymphocytes in HIV disease associates with opportunistic infections. Since diverse CD4 T cell clones respond to an opportunistic pathogen, we asked whether CD4 depletion deletes selected clones in the repertoire (vertical depletion) or it affects all clones by reducing the cell number in each progeny without affecting the overall number of clones (horizontal depletion). Understanding this point may help explain the mode of CD4 depletion and the mode of immunoreconstitution after therapy. Therefore we examined the CD4 T cell repertoire specific for Pneumocystis carinii, a relevant opportunistic pathogen in AIDS, in HIV-infected, asymptomatic individuals. We identified two patients of 36 asymptomatics for lack of proliferation to P. carinii, suggesting selective depletion of specific CD4 cells. To investigate clonal heterogeneity of P. carinii-responsive CD4 lymphocytes, specific CD4 T cell lines were generated and studied by TCR BV gene family usage and CDR3 length analysis (spectratyping). Clonal heterogeneity was similar in antigen-specific CD4 lines generated from P. carinii non-responding HIV seropositives and from controls. Thus, despite undetectable response to the pathogen, residual specific cells probably prevent overt infection and, when expanded in vitro, exhibit a clonal diversity similar to normal controls. These findings suggest a horizontal, rather than vertical, depletion in these asymptomatic patients.


Vanadium Nitride Nanowire Supported SnS2 Nanosheets with High Reversible Capacity as Anode Material for Lithium Ion Batteries.
The vulnerable restacking problem of tin disulfide (SnS2) usually leads to poor initial reversible capacity and poor cyclic stability, which hinders its practical application as lithium ion battery anode (LIB). In this work, we demonstrated an effective strategy to improve the first reversible capacity and lithium storage properties of SnS2 by growing SnS2 nanosheets on porous flexible vanadium nitride (VN) substrates. When evaluating lithium-storage properties, the three-dimensional (3D) porous VN coated SnS2 nanosheets (denoted as CC-VN@SnS2) yield a high reversible capacity of 75% with high specific capacity of about 819 mAh g(-1) at a current density of 0.65 A g(-1). Remarkable cyclic stability capacity of 791 mAh g(-1) after 100 cycles with excellent capacity retention of 97% was also achieved. Furthermore, discharge capacity as high as 349 mAh g(-1) is still retained after 70 cycles even at a elevated current density of 13 A g(-1). The excellent performance was due to the conductive flexible VN substrate support, which provides short Li-ion and electron pathways, accommodates large volume variation, contributes to the capacity, and provides mechanical stability, which allows the electrode to maintain its structural stability.


Role of pro- and anti-inflammatory phenomena in the physiopathology of type 2 diabetes and obesity.
In obesity, persistent low-grade inflammation is considered as a major contributor towards the progression to insulin resistance and type 2 diabetes while in lean subjects the immune environment is non-inflammatory. Massive adipose tissue (AT) infiltration by pro-inflammatory M1 macrophages and several T cell subsets as obesity develops leads to the accumulation - both in the AT and systemically - of numerous pro-inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor α, IL-17 and IL-6 which are strongly associated with the progression of the obese phenotype towards the metabolic syndrome. At the same time, anti-inflammatory M2 macrophages and Th subsets producing the anti-inflammatory cytokines IL-10, IL-5 and interferon-γ, including Th2 and T-reg cells are correlated to the maintenance of AT homeostasis in lean individuals. Here, we discuss the basic principles in the control of the interaction between the AT and infiltrating immune cells both in the lean and the obese condition with a special emphasis on the contribution of pro- and anti-inflammatory cytokines to the establishment of the insulin-resistant state. In this context, we will discuss the current knowledge about alterations in the levels on pro- and anti-inflammatory cytokines in obesity, insulin resistance and type 2 diabetes mellitus, in humans and animal models. Finally, we also briefly survey the recent novel therapeutic strategies that attempt to alleviate or reverse insulin resistance and type 2 diabetes via the administration of recombinant inhibitory antibodies directed towards some pro-inflammatory cytokines.


Evaluation of embryonic and perinatal myosin gene mutations and the etiology of congenital idiopathic clubfoot.
Congenital idiopathic clubfoot is the most common musculoskeletal birth defect that develops during the fetal period, but with no known etiology. MYH 2, 3, 7, and 8 are expressed embryonically or perinatally, the period during which congenital idiopathic clubfoot develops; are all components of Type II muscle, which is consistently decreased in clubfoot patients; and are associated with several muscle contracture syndromes that have associated clubfoot deformities. In this study, we hypothesized that a mutation in an embryonic or perinatal myosin gene could be associated with congenital idiopathic clubfoot. We screened the exons, splice sites, and predicted promoters of 24 bilateral congenital idiopathic clubfoot patients and 24 matched controls in MYH 1, 2, 3, and 8 via sequence-based analysis, and screened an additional 76 patients in each discovered SNP. Although many single-nucleotide polymorphisms were found; none proved to be significantly associated with the phenotype of congenital idiopathic clubfoot. Also, no known mutations that cause distal arthrogryposis syndromes were found in the congenital idiopathic clubfoot patients. These findings demonstrate that congenital idiopathic clubfoot has a different pathophysiology than the clubfoot seen in distal arthrogryposis syndromes, and defects in myosin are most likely not directly responsible for the development of congenital clubfoot. Given the complexity of early myogenesis, many regulatory candidate genes remain that could cause defects in the hypaxial musculature that is invariably observed in congenital idiopathic clubfoot. This study further differentiates congenital idiopathic clubfoot as distinct from other complex genetic syndromes that can present with similar deformities, and thus facilitates further research to improve the clinical diagnosis and treatment of congenital idiopathic clubfoot.


Enhanced production of prodigiosin-like pigment from Serratia marcescens SMdeltaR by medium improvement and oil-supplementation strategies.
Serratia marcescens SMdeltaR, an SpnR-defective isogenic mutant of S. marcescens SS-1, was used to produce a prodigiosin-like pigment (PLP). Luria-Bertani (LB) broth, frequently used for prodigiosin biosynthesis with S. marcescens strains, was modified by increasing the concentrations of tryptone and yeast extract while completely removing NaCl from the medium. The resulting modified LB (MLB) medium achieved an almost 3.0-fold increase in PLP yield (152 mg l(-1)) when compared with the original LB broth. The addition of vegetable oils (2-6% [v/v]) to the fermentation broth markedly enhanced PLP production. PLP yields of 525, 579, and 790 mg l(-1) were obtained when the MLB medium was supplemented with 4% soybean oil, 4% olive oil and 6% sunflower oil, respectively. PLP production was found to be positively correlated with extracellular surface emulsification activity, suggesting a link between the PLP production and the presence of biosurfactant. This work shows that the optimal medium for PLP yield was sunflower oil (6%)-supplemented MLB medium, which resulted in an approximately 14-fold higher PLP yield than that in LB broth. Mass spectrometry and NMR analysis indicated that the PLP product is a prodigiosin derivative, called undecylprodigiosin.


[The "hospital review" in 1865: the first journal for hospital service in Hungary].
This article is a concise history of the first Hungarian journal for hospital medicine published in Pozsony (Bratislava, Pressburg) from the year 1865. The editorial board of the Kórházi Szemle (Hospital Review) consisting of young physicians (Zlamál, Gotthard, Kanka) attempted to give a complete overview on Hungarian hospital research, including new ways of therapies and hospital statistics as well. Analysing the publications of the journal author concludes, that the hospital of Pozsony (Bratislava) founded in 1864 represented a rather high niveau of healing. The first tracheotomies, and the first histologic tests have been performed here in the region.


Association between patient attitudes towards deprescribing and subsequent prescription changes.
Deprescribing is an essential component of safe prescribing, especially for people with higher levels of polypharmacy. Identifying individuals prepared to consider medicine changes may facilitate deprescribing-orientated reviews. We aimed to explore the relationship between revised patients' attitudes towards deprescribing (rPATD) scores and medication changes in older people prescribed ≥15 medicines. A secondary analysis of rPATD scores and prescription data from a cluster randomised controlled trial of a GP-delivered, deprescribing-orientated medication review was conducted. The association between number of medicines stopped, started and changed and baseline rPATD scores was assessed using Poisson regression, adjusting for patient age, gender, study group allocation, baseline number of medicines and effects of clustering. Participants (n = 404) had a mean age of 76.4 years and were prescribed a mean of 17.1 medicines at baseline. Willingness to stop a medicine was associated with higher rates of both deprescribing (IRR: 1.40; 95% CI: 1.06-1.84) and initiating medicines (IRR: 1.43; 95% CI: 1.09-1.88). Satisfaction with current medicines was associated with a lower rate of deprescribing (IRR: 0.69; 95% CI: 0.57-0.85). The rPATD questionnaire could be used as part of a deprescribing intervention to identify participants who may be prepared to engage in deprescribing, enabling more efficient use of clinician time during complex consultations.


Single In x Ga1-x As nanowire/p-Si heterojunction based nano-rectifier diode.
Nanoscale power supply units will be indispensable for fabricating next generation smart nanoelectronic integrated circuits. Fabrication of nanoscale rectifier circuits on a Si platform is required for integrating nanoelectronic devices with on-chip power supply units. In the present study, a nanorectifier diode based on a single standalone In x Ga1-x As nanowire/p-Si (111) heterojunction fabricated by metal organic chemical vapor deposition technique has been studied. The nanoheterojunction diodes have shown good rectification and fast switching characteristics. The rectification characteristics of the nanoheterojunction have been demonstrated by different standard waveforms of sinusoidal, square, sawtooth and triangular for two different frequencies of 1 and 0.1 Hz. Reverse recovery time of around 150 ms has been observed in all wave response. A half wave rectifier circuit with a simple capacitor filter has been assembled with this nanoheterojunction diode which provides 12% output efficiency. The transport of carriers through the heterojunction is investigated. The interface states density of the nanoheterojunction has also been determined. Occurrence of output waveforms incommensurate with the input is attributed to higher series resistance of the diode which is further explained considering the dimension of p-side and n-side of the junction. The sudden change of ideality factor after 1.7 V bias is attributed to recombination through interface states in space charge region. Low interface states density as well as high rectification ratio makes this heterojunction diode a promising candidate for future nanoscale electronics.


The ethical judgment of animal research.
One hundred sixty subjects acted as members of a hypothetical Institutional Animal Care and Use Committee and evaluated five proposals in which animals were to be used for research or educational purposes. They were asked to approve or reject the proposals and to indicate what factors were important in reaching their ethical decisions. Gender and differences in personal moral philosophy were related to approval decisions. The reasons given for the decisions fell into three main categories: metacognitive statements, factors related to the animal, and factors related to the design of the experiment.


Are infant feeding options that are recommended for mothers with HIV acceptable, feasible, affordable, sustainable and safe? Pregnant women's perspectives.
To investigate pregnant women's views on infant feeding options recommended for HIV-infected women. A structured interview survey complemented with focus group discussions. Antenatal clinics in Moshi urban and rural districts of Tanzania. Five hundred pregnant women participated in the interview survey and 46 pregnant women participated in six focus group discussions. Participating women reported that they would change to an alternative infant feeding method if they were found to be HIV-infected and were advised to do so. Cow's milk was regarded as the most feasible infant feeding method for local HIV-infected mothers. Infant feeding formula was regarded as too costly, but if recommended by health workers and distributed free of charge, the majority of the women (82%) were confident that they would then choose this option. In the focus group discussions, women were less optimistic and expressed great concern for the social consequences of not breast-feeding. The safety of exclusive breast-feeding was questioned. Less common infant feeding methods, such as expressed heat-treated breast milk and wet-nursing, were not regarded as viable options. Several social barriers to replacement feeding were identified in the focus group discussions, including possible lack of support from partner and potential negative reactions from the community. Future research on infant feeding options should include the broader cultural context and the psychological stress that HIV-infected women face when choosing infant feeding methods.


Reoperation for bleeding following coronary artery bypass surgery with special focus on long-term outcomes.
Objectives: We studied the incidence and risk factors of reoperation for bleeding following CABG in a nationwide cohort with focus on long-term complications and survival. Design: A retrospective study on 2060 consecutive, isolated CABG patients operated 2001-2016. Outcome of reoperated patients (n = 130) were compared to non-reoperated ones (n = 1930), including major adverse cardiac and cerebrovascular events (MACCE) and overall survival. Risk factors for reoperation were determined using multivariate logistic regression and a Cox proportional hazards model to assess prognostic factors of long-term survival. Median follow-up was 7.6 years. Results: One hundred thirty patients (6.3%) were reoperated with an annual decrease of 4.1% per year over the study period (p=.04). Major complications (18.5 vs. 9.6%) and 30-day mortality (8.5 vs. 1.9%,) were higher in the reoperation group (p<.001). The use of clopidogrel preoperatively (OR 3.62, 95% CI: 1.90-6.57) and reduced left ventricular ejection fraction (OR 2.23, 95% CI: 1.25-3.77) were the strongest predictors of reoperation, whereas off-pump surgery was associated with a lower reoperation risk (OR 0.44, 95% CI: 0.22-0.85). After exluding patients that died within 30 days postoperatively, no difference in long-term survival or freedom from MACCE was found between groups, and reoperation was not an independent risk factor for long-term mortality in multivariate analysis. Conclusions: The reoperation rate in this study was relatively high but decreased significantly over time. Reoperation was associated with twofold increased risk for major complications and fourfold 30-day mortality, but comparable long-term MACCE and survival rates. This implies that if patients survive the first 30 days following reoperation, their long-term outcome is comparable to non-reoperated patients.


Correlations in scale-free networks: tomography and percolation.
We discuss three related models of scale-free networks with the same degree distribution but different correlation properties. Starting from the Barabási-Albert construction based on growth and preferential attachment we discuss two other networks emerging when randomizing it with respect to links or nodes. We point out that the Barabási-Albert model displays dissortative behavior with respect to the nodes' degrees, while the node-randomized network shows assortative mixing. These kinds of correlations are visualized by discussing the shell structure of the networks around an arbitrary node. In spite of different correlation behaviors, all three constructions exhibit similar percolation properties. This result for percolation is also detected for a network with finite second moment and its corresponding randomized models.


Outcomes in patients with indeterminate pulmonary nodules undergoing resection for colorectal liver metastases.
This study aimed to assess outcomes in patients who underwent hepatic resection for colorectal liver metastases (CRLM) with subcentimetre indeterminate pulmonary nodules (IPN) and to devise a management pathway for these patients. Patients undergoing CRLM resection from January 2006 to December 2010 were included. Survival differences following liver resection in patients with and without IPN were determined. A total of 184 patients were included, 30 of whom had IPN. There were no significant differences between the IPN and non-IPN groups in terms of demographics, surgery and pathological factors. There were no significant differences between patients with and without IPN with respect to disease-free (P= 0.190) and overall (P= 0.710) survival. Fifteen patients with IPN progressed to metastatic lung disease over a median period of 10 months (range: 3-18 months); six of these patients underwent lung resection. Of the remaining 15 patients with IPN, eight showed no IPN progression and subsequent CT scans did not identify IPN in the remaining seven. Colorectal liver metastases patients with IPN who have resectable disease should be treated with liver resection and should be subject to intensive surveillance post-resection. Although 50% of these patients will progress to develop lung metastases, this does not appear to influence survival following liver resection.


Clinical-morphological correlation of nasal obstruction with skull base development and otitis media. An experimental study.
Morphological changes of the middle ear were investigated by means of microotoscopy and scanning electron microscopy in 40 developing Albino rats. In 20 one nostril (group B) and in 20 both nostrils (group C) had been experimentally obstructed. 20 rats were used as controls (group A). Microotoscopy and scanning electron microscopy on the middle ear mucosa were performed when the animals were 2 months old, i.e. at 90% of their development. At microotoscopy the tympanic membranes, homolateral to the obstructed nostril, proved to be abnormal in 81% of group B rats and in almost all rats belonging to group C. Scanning electron microscopy, performed after the bullae had been removed, showed the following epithelial surface changes of the middle ear homolaterally to the obstructed nostril: (a) a significant increase of nonciliated elements with a secretory behavior as compared to controls, even of the floor where normally a large number of ciliated cells is present; (b) several ciliated cells were destroyed and their cilia were irregular and untidy; (c) thick mucous secretions covered the floor of the tympanic bulla; and (d) squamous metaplasia of the hypotympanic epithelium. Extrarotation of the eustachian tubes and developmental abnormalities of the skull base in growing rats, caused by nasal obstruction, seem to be able to induce pathological events of the middle ear.


The genes encoding bovine SP-A, SP-D, MBL-A, conglutinin, CL-43 and CL-46 form a distinct collectin locus on Bos taurus chromosome 28 (BTA28) at position q.1.8-1.9.
Collectins are a group of C-type lectins involved in the innate immune system, where they mediate and modulate clearance of pathogens. The health status of cattle is of major economical and ethical concern; therefore, the study of bovine collectins is of importance. The collectins conglutinin, CL-43 and CL-46 are only present in Bovidae and the characterization of their genes indicates that they are structural descendants of another collectin, lung surfactant protein D (SP-D). In this study, we assembled BAC clones into a contig spanning 330-1150 kb, which includes the bovine genes encoding the collectins SP-A (SFTPA), SP-D (SFTPD), mannan-binding lectin A (MBL1), CL-43 (COLEC9), CL-46 (COLEC13) and conglutinin (COLEC8). In the same contig, we also identified a gene that potentially encodes a novel conglutinin-like collectin (COLEC14). The arrangement of STFPA, SFTPD and MBL1 is homologous to the organization found in humans and mice, whereas the Bovidae-specific collectin genes, COLEC8, COLEC9 and COLEC13, extend from SFTPD. Proximal to the collectin locus at BTA28q1.8-1.9, and included in the contig, we found the microsatellite IDVGA8, which may be a valuable marker for tracking polymorphisms in the linked collectin genes.


Ions at the air-water interface: an end to a hundred-year-old mystery?
Availability of highly reactive halogen ions at the surface of aerosols has tremendous implications for the atmospheric chemistry. Yet neither simulations, experiments, nor existing theories are able to provide a fully consistent description of the electrolyte-air interface. In this Letter a new theory is proposed which allows us to explicitly calculate the ionic density profiles, the surface tension, and the electrostatic potential difference across the solution-air interface. Predictions of the theory are compared to experiments and are found to be in excellent agreement. The theory also sheds new light on one of the oldest puzzles of physical chemistry--the Hofmeister effect.


Development of a dual MCP framing camera for high energy x-rays.
Recently developed diagnostic techniques at LLNL require recording backlit images of extremely dense imploded plasmas using hard x-rays, and demand the detector to be sensitive to photons with energies higher than 50 keV [R. Tommasini et al., Phys. Phys. Plasmas 18, 056309 (2011); G. N. Hall et al., "AXIS: An instrument for imaging Compton radiographs using ARC on the NIF," Rev. Sci. Instrum. (these proceedings)]. To increase the sensitivity in the high energy region, we propose to use a combination of two MCPs. The first MCP is operated in a low gain regime and works as a thick photocathode, and the second MCP works as a high gain electron multiplier. We tested the concept of this dual MCP configuration and succeeded in obtaining a detective quantum efficiency of 4.5% for 59 keV x-rays, 3 times larger than with a single plate of the thickness typically used in NIF framing cameras.


Parathyroid hormone-independent hypercalcemia in an infant with renal dysplasia: possible role of PTHrP.
Parathyroid hormone (PTH)-independent hypercalcemia in patients with chronic kidney failure is a rare and poor understood entity. We report the case of an infant with stage III chronic kidney failure secondary to multicystic dysplastic kidney disease, who presented at 3 months of life with severe hypercalcemia, suppressed PTH, and elevated PTH-related peptide. Malignancy was discarded, and the patient was treated twice with bisphosphonates with an initial partial response. During follow-up, the calcium levels descended. To date, he has maintained normal serum calcium level for 1 year after discharge. The presence of PTH-related peptide may play a role in hypercalcemia associated to multicystic dysplastic kidney disease possibly by the overproduction of this peptide in the kidney.


Submersible UV-Vis spectroscopy for quantifying streamwater organic carbon dynamics: implementation and challenges before and after forest harvest in a headwater stream.
Organic material, including total and dissolved organic carbon (DOC), is ubiquitous within aquatic ecosystems, playing a variety of important and diverse biogeochemical and ecological roles. Determining how land-use changes affect DOC concentrations and bioavailability within aquatic ecosystems is an important means of evaluating the effects on ecological productivity and biogeochemical cycling. This paper presents a methodology case study looking at the deployment of a submersible UV-Vis absorbance spectrophotometer (UV-Vis spectro::lyzer model, s::can, Vienna, Austria) to determine stream organic carbon dynamics within a headwater catchment located near Campbell River (British Columbia, Canada). Field-based absorbance measurements of DOC were made before and after forest harvest, highlighting the advantages of high temporal resolution compared to traditional grab sampling and laboratory measurements. Details of remote deployment are described. High-frequency DOC data is explored by resampling the 30 min time series with a range of resampling time intervals (from daily to weekly time steps). DOC export was calculated for three months from the post-harvest data and resampled time series, showing that sampling frequency has a profound effect on total DOC export. DOC exports derived from weekly measurements were found to underestimate export by as much as 30% compared to DOC export calculated from high-frequency data. Additionally, the importance of the ability to remotely monitor the system through a recently deployed wireless connection is emphasized by examining causes of prior data losses, and how such losses may be prevented through the ability to react when environmental or power disturbances cause system interruption and data loss.


Dynamic Interactions between a Silica Sphere and Deformable Interfaces in Organic Solvents Studied by Atomic Force Microscopy.
Recent studies have successfully measured surface forces using atomic force microscope (AFM) and modeled surface deformations using the Stokes-Reynolds-Young-Laplace (SRYL) equations for particle-droplet, particle-bubble, droplet-droplet, and bubble-bubble systems in various solutions. The current work focuses on interactions between spherical silica particles and a viscoelastic interface of water droplets in crude oil. The self-assembly of surface active natural polyaromatic molecules (NPAMs) at the oil-water interface has previously been shown to change a viscous dominant oil-water interface to an elastic dominant interface upon aging, due to gradual formation of rigid interfacial networks. AFM was used to measure the interactions between a small silica sphere (D ≈ 8 μm) and a deformable water droplet (D ≈ 70 μm), which exhibits time-dependent interfacial viscoelasticity in NPAM solutions. Unlike the systems studied previously, the measured deformation shown as a repulsive force over the region of constant compliance could not be modeled adequately by the conventional SRYL equations which are applicable only to purely Laplacian interfaces. As the water droplet ages in NPAM solutions, a rigid "skin" forms at the oil-water interface, with the interface exhibiting increased elasticity. Over a short aging period (up to 15 min in NPAM-in-toluene solution), interfacial deformation is well predicted by the SRYL model. However, upon further exposure to the NPAM solution, droplet deformation is overpredicted by the model. Physical properties of this mechanical barrier as a function of interfacial aging were further investigated by measuring interfacial tension, dilatational rheology, and interfacial "crumpling" (non-smooth, non-Laplacian interface) upon droplet volume reduction. By introducing a viscoelasticity parameter to account for interfacial stiffening and using experimentally determined elasticity, we are able to correct this discrepancy and predict droplet deformation under AFM cantilever compression. This parameter appears to be important for modeling non-Laplacian systems of significant viscoelastic contributions, such as biological cell membranes or polymer blends.


Effect of dexamethasone on experimental Escherichia coli mastitis in the cow.
The effect of intramuscular administration of dexamethasone on milk production and on several clinical and hematologic indicators in cows with experimental Escherichia coli mastitis was studied. Two groups of three cows each were intramammarily inoculated with 20 x 10(5) cfu E. coli 0101 K99 F41 in rear quarters. Immediately after inoculation one groups received 30 mg dexamethasone intramuscularly, whereas the other group was injected similarly with pyrogen-free saline. Fourteen days later milk production losses were markedly less in the dexamethasone-treated group. Dexamethasone treatment reduced local clinical signs of inflammation, significantly increased rectal temperatures, and diminished inhibition of rumen amplitude during the acute phase of infection. Moreover, cows treated with dexamethasone showed diminished neutropenia, more pronounced hypozincemia, and delayed onset in the decrease in plasma iron concentrations. Possible mechanisms by which these changes are accomplished are discussed.


Tunable SnSe2 /WSe2 Heterostructure Tunneling Field Effect Transistor.
The burgeoning 2D semiconductors can maintain excellent device electrostatics with an ultranarrow channel length and can realize tunneling by electrostatic gating to avoid deprivation of band-edge sharpness resulting from chemical doping, which make them perfect candidates for tunneling field effect transistors. Here this study presents SnSe2 /WSe2 van der Waals heterostructures with SnSe2 as the p-layer and WSe2 as the n-layer. The energy band alignment changes from a staggered gap band offset (type-II) to a broken gap (type-III) when changing the negative back-gate voltage to positive, resulting in the device operating as a rectifier diode (rectification ratio ~104 ) or an n-type tunneling field effect transistor, respectively. A steep average subthreshold swing of 80 mV dec-1 for exceeding two decades of drain current with a minimum of 37 mV dec-1 at room temperature is observed, and an evident trend toward negative differential resistance is also accomplished for the tunneling field effect transistor due to the high gate efficiency of 0.36 for single gate devices. The ION /IOFF ratio of the transfer characteristics is >106 , accompanying a high ON current >10-5 A. This work presents original phenomena of multilayer 2D van der Waals heterostructures which can be applied to low-power consumption devices.


Proposed Constitutive Law of Uniaxial Compression for Concrete under Deterioration Effects.
In order to study the ductile deformation characteristics and failure process of plain concrete under uniaxial compression, this paper proposes a new constitutive model. The new model was used to fit and analyze the constitutive curve of concrete under uniaxial compressive under various degradation forms and was compared with the traditional constitutive models. Finally, the new model was used to quantitatively analyze and predict the stress-strain curve of concrete in different degradation periods of a set of freeze-thaw measured data. The results show that, compared with the traditional constitutive model, the new model is simple in form and has few parameters, and the numerical value of the parameter can reflect the ductile deformation capacity of concrete. The fitting curve of the new model has the highest fitting degree with the measured stress-strain curve of concrete, and the goodness of fit (R2) is also the largest. The new model is suitable for fitting the stress-strain curve of concrete under uniaxial compression under various deteriorating forms, and the degree of fit between the constitutive prediction curve and the measured curve is high. It can be seen from the fitting results of the new model parameters that the ductile deformation capacity of concrete decreases first and then increases slightly, which is inconsistent with the law of gradual deterioration of strength. There is a minimum moment of ductility deformation capacity of concrete (MDC). The MDC of O-C40 concrete is about 114 freeze-thaw cycles, and the MDC of O-C50 concrete is about 116 freeze-thaw cycles; the degree of fit between the constitutive prediction curve and the measured curve is high. We hope that the improvement mentioned offers valid reference to the study of ductile deformation characteristics and failure process of compressed concrete under different deterioration forms.


[Molecular mechanisms underlying fracture repair].
In the developed countries including Japan, population ageing has remarkably proceeded. Among such societies, fractures in the elder have raised as the issue, which should be resolved. To facilitate fracture healing in the clinical situations, it is essential to understand the molecular mechanisms underlying fracture repair. In this review, the molecular mechanisms of fracture repair, which have been recently reported, will be introduced. These clarifications on molecular mechanisms may open the new window for the treatment to accelerate fracture healing.


The depletion of MARVELD1 leads to murine placenta accreta via integrin β4-dependent trophoblast cell invasion.
The placenta is a remarkable organ, it serves as the interface between the mother and the fetus. Proper invasion of trophoblast cells is required for a successful pregnancy. Previous studies have found that the adhesion molecule integrin β4 plays important roles during trophoblast cell invasion. Here, we found that the overall birth rate of the MARVELD1 knockout mouse is much lower than that of the wild-type mouse (p < 0.001). In E18.5 MARVELD1 knockout mice, we observed an over-invasion of trophoblast cells, and indeed, the pregnant mice had a partial placenta accreta phenotype. The HTR8/SVneo cell line was used as an in vitro model to elucidate the underlying mechanisms of MARVELD1-mediated trophoblast invasion. We detected a diminished expression of integrin β4 upon the downregulation of MARVELD1 and enhanced migrate and invasive abilities of trophoblast cells both in vivo and in vitro. The integrin β4 rescue assay also supported the results. In conclusion, this study found that MARVELD1 mediated the invasion of trophoblast cells via regulating the expression of integrin β4 during placenta development.


Genomic subtypes of cutaneous melanoma have distinct metabolic profiles: A single-cell transcriptomic analysis.
Genomic profiling previously classified melanoma into distinct subtypes based on the presence or absence of mutations in driver genes, but metabolic differences between and within these groups have yet to be thoroughly analyzed. Thus, the objective of the present study is to provide the first effort to holistically characterize the metabolic landscape of qualified melanoma genomic subtypes at single-cell resolution. Expression data for a total of 1145 malignant cells sourced from NRAS(Q61L), BRAF(V600E), and NRAS/BRAF WT melanomas were retrieved from the Broad Single Cell Portal. Metabolic activity was interrogated by pathway scoring and gene set enrichment analysis. A total of 53 metabolic pathways were differentially regulated in at least one melanoma genomic subtype. Some notable findings include: BRAF/NRAS WT cells were enriched for fatty acid biosynthesis and depleted for metabolism of alanine, aspartate, and glutamate; BRAF(V600E) melanoma cells were enriched for beta-alanine metabolism and depleted for phenylalanine metabolism; NRAS(Q61L) melanoma cells were enriched for steroid biosynthesis and depleted for linoleic acid metabolism. Primary limitations include the total quantity of single cells and breadth of available genomic subtypes plus inherent noisiness of the applied methodologies. Nonetheless, these findings nominate novel, testable therapeutic targets.


Pharmacology of a new orally active antiallergic: pyrido[1,2-a]pyrimidine, ucb L140 (CHINOIN 1045) in rats.
ucb L140 (CHINOIN 1045) has been tested in various rat anaphylaxis systems. In models of passive cutaneous anaphylaxis (PCA), passive peritoneal anaphylaxis (PPA) and anaphylactic bronchospasms, ucb L140 appears to be more potent than sodium cromoglycate (DSCG). Upon oral administration, ucb L140 exhibits a marked inhibition of these anaphylactic reactions. Sensitized rat mast cells in vitro display a decreased Nippostrongylus-induced histamine release when treated with a concentration of ucb L140 three times smaller than DSCG. In PCA testing after intravenous administration of ucb L140 a cross-tachyphylaxis with DSCG was observed. These results suggest that the action of ucb L140 is similar to that of DSCG in inhibiting the release of allergic mediators from mast cells and therefore may present antiallergic activity.


Facial nerve paralysis. 2. 'All that palsies is not Bell's'.
Management of the patient with facial nerve paralysis challenges the diagnostic skills and clinical judgment of the attending physician. The clinician should not assume that all facial paralysis is Bell's palsy; the disease possibilities are broad and fascinating. Therapeutic options are still being evaluated, debated, and assessed. Appropriate management of the patient with facial nerve paralysis requires a complete history and precise examination.


Iodine intake as a risk factor for BRAF mutations in papillary thyroid cancer patients from an iodine-replete area.
Both deficient and excessive iodine intake leads to thyroid disease, which shows U-shaped curves. Our previous study showed that a relatively low [urinary iodine concentration (UIC) <300 μg/L] and extremely excessive (UIC ≥ 2500 μg/L) iodine intake were associated with thyroid cancer in Korea, an iodine-replete area. Papillary thyroid cancer (PTC) accounts for more than 97 % of thyroid cancer and 80% or more PTC cases harbor the BRAF mutation in Korea. We aimed to investigate the relationship between iodine intake and the prevalence of the BRAF mutation in PTC in Korea. UIC was measured by inductively coupled plasma mass spectrometry. The BRAF mutation was detected using both allele-specific polymerase chain reaction and mutant enrichment with 3'-modified oligonucleotide sequencing. Risk factors for the occurrence of BRAF mutations in PTC were evaluated using multivariate logistic regression models. The median UIC in all patients with PTC was 287 μg/L (range from 7 to 7, 426 μg/L). Nearly half of the patients (102/215, 47%) belonged to the excessive iodine intake category (UIC ≥ 300 μg/L) according to the WHO iodine recommendations. The frequency of BRAF mutations was lowest in the 300-499 μg/L UIC group; it was significantly different compared to the relatively low (UIC < 300 μg/L) and more than excessive (UIC ≥ 500 μg/L) iodine intake groups. UIC was an independent predictor for BRAF mutations in PTC. The multivariate-adjusted odds ratios (95% confidence intervals) in the relatively low and more than excessive iodine intake groups for the BRAF mutation were 4.761 (1.764-12.850) and 6.240 (2.080-18.726), respectively, compared to the 300-499 μg/L UIC group. Relatively low iodine intake and more than excessive iodine intake seem to be significant risk factors for the occurrence of BRAF mutations in the thyroid and, therefore, may be risk factors for the development of PTC in an iodine-replete area.


Molecular diagnosis of congenital bilateral absence of the vas deferens: analyses of the CFTR gene in 64 French patients.
Congenital bilateral absence of the vas deferens is a congenital reproductive disorder that affects about one in 1000 male individuals. Screening of the entire coding and flanking sequences of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 64 males with CBAVD revealed that in only 23% CBAVD was caused by two CFTR mutations. The 5T allele in one copy, that causes reduced levels of the normal CFTR protein, in combination with a CFTR mutation in the other copy, was one of the most common causes of CBAVD. Twenty six per cent of men with CBAVD had the 5T allele. The presence of only one CFTR mutation or the 5T allele in 34% of patients suggests that undetected changes in CFTR may be involved in CBAVD. These molecular defects are probably mutations with partial penetrance. Moreover, the high proportion (20%) of patients with CBAVD who did not have CFTR mutations or the 5T allele allows to propose that another gene or genes could be responsible for CBAVD. In these cases, in vitro fertilization may be required and the genetic counselling appears to be very complex and additional studies, including CFTR mRNA and linkage analyses, are required to resolve these questions.


6th International Congress of the Croatian Society of Nuclear Medicine in Opatija 2008.
The 6th International Congress of the Croatian Society of Nuclear Medicine gives an overview of present-day nuclear medicine. The congress shows that Croatian nuclear medicine follows the general trends of the European nuclear medicine.


Comparisons and correlations of pain intensity and respiratory and peripheral muscle strength in the pre- and postoperative periods of cardiac surgery.
To evaluate respiratory and peripheral muscle strength after cardiac surgery. Additionally, we compared the changes in these variables on the third and sixth postoperative days. Forty-six patients were recruited, including 17 women and 29 men, with a mean age of 60.50 years (SD = 9.20). Myocardial revascularization surgery was performed in 36 patients, replacement of the aortic valve in 5 patients, and replacement of the mitral valve in 5 patients. A significant reduction in respiratory and peripheral muscle strength and a significant increase in pain intensity were observed on the third and sixth postoperative days (p < 0.05), except for the variable maximal inspiratory pressure; on the sixth postoperative day, maximal inspiratory pressure values were already similar to the preoperative and predicted values (p > 0.05). There was an association between peripheral muscle strength, specifically between maximal expiratory pressure preoperatively (rs = 0.383; p = 0.009), on the third postoperative day (rs = 0.468; p = 0.001) and on the sixth postoperative day (rs = 0.311; p = 0.037). The effect sizes were consistently moderate-to-large for respiratory muscle strength, the Medical Research Council scale and the visual analog scale, in particular between preoperative assessment and the sixth postoperative day. There is a decrease in respiratory and peripheral muscle strength after cardiac surgery. In addition, maximal expiratory pressure is the variable that is most associated with peripheral muscle strength. These variables, especially respiratory and peripheral muscle strength, should be considered by professionals working in the intensive care setting.


Pathogen-induced food evasion behavior in Drosophila larvae.
Recognizing a deadly pathogen and generating an appropriate immune reaction is essential for any organism to survive in its natural habitat. Unlike vertebrates and higher primates, invertebrates depend solely on the innate immune system to defend themselves from an attacking pathogen. In this study, we report a behavioral defense strategy observed in Drosophila larvae that helps them escape and limit an otherwise lethal infection. A bacterial infection in the gut is sensed by the larval central nervous system, which generates an alteration in the larva's food preference, leading it to stop feeding and move away from the infectious food source. We have also found that this behavioral response is dependent on the internal nutritive state of the larvae. Using this novel behavioral assay as a read-out, we further identified hugin neuropeptide to be involved in the evasion response and detection of bacterial signals.


Two new compounds from Verbena bonariensis.
Two new compounds verboncin A (1) and verboncin B (4) and 14 known compounds (2-3 and 5-16) were isolated from Verbena bonariensis, and these 14 compounds were first obtained from this plant. Their chemical structures were established by one and two-dimensional NMR and HRESIMS analysis and the results were compared with literature values. The absolute configuration of 1 was determined by calculating electronic circular dichroism (ECD). The cytotoxicity of some of the compounds against MCF-7, HCT-116, MDA-MB-231, and SW620 human cancer cell lines were evaluated, in which compound 4 showed negligible cytotoxic activity with an IC50 value of 68.08 ± 0.35 µM against the MCF-7 cell line.


Long-term results following an anatomically based surgical technique for resection of colon cancer: a comparison with results from complete mesocolic excision.
Complete mesocolic excision (CME) has been advocated as likely to improve the long-term oncological outcome of colon cancer resection, although there is a paucity of long-term results in the literature. The aim of this study was to supplement our previously published results on colon cancer resection based on a standardized technique of precise dissection along anatomical planes with high vascular ligation and to compare our long-term results with those of recent European studies of CME. Data were drawn from a prospective hospital registry of consecutive resections for colon cancer between 1996 and 2007, including follow-up to the end of 2012. The principal outcomes from potentially curative resections were 5-year Kaplan-Meier rates of local recurrence, systemic recurrence, overall survival and cancer-specific survival. Secondary outcomes for all resections were postoperative complications, number of lymph nodes retrieved and R0 status. For 779 potentially curative resections the local recurrence rate was 2.1% (95% CI 1.3-3.4), the systemic recurrence rate was 10.2% (95% CI 8.1-12.7), the 5-year overall survival rate was 76.2% (95% CI 73.0-79.0) and the cancer-specific survival rate was 89.8% (95% CI 87.3-91.9). For all 905 resections, rates of 14 surgical complications were low and not dissimilar to those in a comparable study. The median lymph node count was 15 (range 0-113). R0 status was confirmed in 883/905 patients (97.6%; 95% CI 96.4-98.5). For colon cancer, meticulous dissection along anatomical planes together with high vascular ligation results in few complications, a high R0 rate, low recurrence and high survival.


Immunostimulant effects of diet supplementation with yellow (Pouteria campechiana), white (Casimiroa edulis), and black (Diospyros digyna) sapote nanocapsules on laying hens: in vitro and in vivo study.
Poultry is commonly infected by different bacteria and parasites in the environment, resulting in increased morbidity and mortality, but immunostimulants have been enhancing non-specific defense mechanisms conferring laying hens' protection. For this purpose, the pulp of yellow (Pouteria campechiana), white (Casimiroa edulis), and black (Diospyros digyna) sapotes were nanoencapsulated (YWB-SN) and evaluated in laying hens' peripheral blood leukocytes to test their addition to the experimental diets at a concentration of 0.5% (5g/kg of dry food) for 1 month (with two samples at days 15 and 30). The YWB-SN were safe when exposed to peripheral blood leukocytes (PBLs). The in vitro experiment showed that these nanocapsules enhanced reactive oxygen species production, and B-SN stimulated phagocytosis activity. Concerning the proinflammatory cytokine (TNF-α) transcription, this gene was upregulated after W-SN stimulation, while B-SN upregulated the IgG gene expression significantly. IgM was upregulated with any YBW-SN in PBLs after 24 h of stimulation. The in vivo study showed a notable B-SN immunostimulation in serum and an upregulation of TNF-α, IgM, and IgG mRNA transcription. Therefore, this study provides a new result of the yellow, white, and black sapote nanocapsules as a functional food for the poultry industry, highlighting the black sapote Diospyros digyna immunostimulant effect.


Comparison of NHANES III and ERS/GLI 12 for airway obstruction classification and severity.
The diagnosis and severity categorisation of obstructive lung disease is determined using reference values. The American Thoracic Society/European Respiratory Society in 2005 recommended the National Health and Nutrition Examination Survey (NHANES) III spirometry prediction equations for patients in USA aged 8-80 years. The Global Lung Initiative 2012 (GLI 12) provided spirometry prediction equations for patients aged 3-95 years. Comparison of the NHANES III and GLI 12 prediction equations for diagnosing and categorising airway obstruction in patients in USA has not been made.We aimed to quantify the differences between NHANES III and GLI 12 predicted values in Caucasians aged 18-95 years, using both mathematical simulation and clinical data. We compared predicted forced expiratory volume in 1 s (FEV1) and lower limit of normal (LLN) FEV1/forced vital capacity (FVC) % for NHANES III and GLI 12 prediction equations by applying both a simulation model and clinical spirometry data to quantify differences in the diagnosis and categorisation of airway obstruction.Mathematical simulation revealed significant similarities and differences between prediction equations for both LLN FEV1/FVC % and predicted FEV1 There are significant differences when using GLI 12 and NHANES III to diagnose airway obstruction and severity in Caucasian patients aged 18-95 years.Similarities and differences exist between NHANES III and GLI 12 for some age and height combinations. The differences in LLN FEV1/FVC % and predicted FEV1 are most prominent in older taller/shorter individuals. The magnitude of the differences can be large and may result in differences in clinical management.


[Activation of NOD-like receptor protein 3 inflammasome mediates inflammatory response and apoptosis in septic intestinal injury model].
To investigate the expression of NOD-like receptor protein 3 (NLRP3) inflammasome in intestinal injury models with different severity of sepsis and the inflammatory response and apoptosis mediated by NLRP3 inflammasome. Human colorectal adenocarcinoma cells (Caco-2) were cultured in vitro. The logarithmic growth phase cells were divided into blank control group (normal culture in complete medium) and lipopolysaccharide (LPS) 1, 2 and 4 mg/L groups (complete medium containing 1, 2 and 4 mg/L LPS, respectively). The supernatant were collected at 6, 12 and 24 hours, and the levels of tumor necrosis factor-α (TNF-α), interleukins (IL-6, IL-1β, IL-18) were detected by enzyme linked immunosorbent assay (ELISA). The apoptotic level of cells was detected by flow cytometry. The cells were harvested, and the real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the mRNA expressions of NLRP3 and silent information regulator 1 (SIRT1). Western blotting was used to detect the protein expressions of NLRP3, SIRT1, caspase-1 and apoptosis-associated speck-like protein (ASC). ELISA results showed that the levels of IL-6, TNF-α, IL-1β, and IL-18 in cell supernatant of LPS groups increased in a dose-dependent and time-dependent manner as compared with the blank control group during the same intervention period. The increase was most significant in LPS 4 mg/L group at 24 hours [IL-6 (ng/L): 3.55±0.06 vs. 0.67±0.09, TNF-α (ng/L): 15.37±0.19 vs. 5.04±0.14, IL-1β (ng/L): 2.26±0.10 vs. 0.56±0.09, IL-18 (ng/L): 433.92±22.55 vs. 93.55±21.13, all P < 0.05]. The results of the apoptotic test showed that, compared with the blank control group, the apoptotic rate of LPS groups increased in a dose-dependent and time-dependent manner, and the apoptotic rate of LPS 4 mg/L group increased most significantly at 24 hours [(14.83±3.73)% vs. (5.87±1.17)%, P < 0.05]. RT-qPCR results showed that the expression level of NLRP3 mRNA was increased, while the expression level of SIRT1 mRNA was decreased with the increase of LPS intervention dose and the prolonging of intervention time. At 24 hours, there were significant differences between LPS 4 mg/L group and blank control group [NLRP3 mRNA (2-ΔΔCt): 8.20±2.82 vs. 1.00±0.36, SIRT1 mRNA (2-ΔΔCt): 0.58±0.01 vs. 1.03±0.06, both P < 0.05]. Western blotting showed that compared with the blank control group, the protein expression levels of NLRP3, caspase-1 and ASC in LPS groups were significantly increased, while the protein expression levels of SIRT1 were significantly decreased. During each intervention period, with the increase of LPS dose, the expressions of NLRP3, caspase-1 and ASC protein increased gradually, while the expression of SIRT1 protein decreased gradually. At 24 hours, the difference between the LPS 4 mg/L group and the blank control group was significant [NLRP3 protein (NLRP3/β-actin): 1.48±0.03 vs. 0.90±0.12, caspase-1 protein (caspase-1/β-actin): 1.18±0.11 vs. 0.72±0.09, ASC protein (ASC/β-actin) : 1.09±0.01 vs. 0.82±0.03, SIRT1 protein (SIRT1/β-actin): 0.48±0.03 vs. 0.76±0.05, all P < 0.05]. In vitro, in the sepsis induced intestinal inflammation model, with the increase of LPS intervention dose and the prolongation of intervention time, intestinal inflammatory response and cell apoptosis showed an increasing trend, which may be related to the up-regulation of NLRP3 inflammasome and its downstream products ASC and caspase-1, and to the down-regulation of SIRT1 expression.


Heat shock factor C2a serves as a proactive mechanism for heat protection in developing grains in wheat via an ABA-mediated regulatory pathway.
High temperature at grain filling can severely reduce wheat yield. Heat shock factors (Hsfs) are central regulators in heat acclimation. This study investigated the role of TaHsfC2a, a member of the monocot-specific HsfC2 subclass, in the regulation of heat protection genes in Triticum aestivum. Three TaHsfC2a homoeologous genes were highly expressed in wheat grains during grain filling and showed only transient up-regulation in the leaves by heat stress but were markedly up-regulated by drought and abscisic acid (ABA) treatment. Overexpression of TaHsfC2a-B in transgenic wheat resulted in up-regulation of a suite of heat protection genes (e.g. TaHSP70d and TaGalSyn). Most TaHsfC2a-B target genes were heat, drought and ABA inducible. Transactivation analysis of two representative targets (TaHSP70d and TaGalSyn) showed that TaHsfC2a-B activated expression of reporters driven by these target promoters. Promoter mutagenesis analyses revealed that heat shock element is responsible for transactivation by TaHsfC2a-B and heat/drought induction. TaHsfC2a-B-overexpressing wheat showed improved thermotolerance but not dehydration tolerance. Most TaHsfC2a-B target genes were co-up-regulated in developing grains with TaHsfC2a genes. These data suggest that TaHsfC2a-B is a transcriptional activator of heat protection genes and serves as a proactive mechanism for heat protection in developing wheat grains via the ABA-mediated regulatory pathway.


The "gag rule" revisited: physicians as abortion gatekeepers.
In this article, I explore this failure [of the therapeutic exception as a compromise device in federal abortion counseling regulations] with an eye toward its broader lessons about the social uses of medical discretion and the difficulty of achieving an abortion compromise in America. I begin by examining the legal underpinning beneath the widespread belief that the "gag rule" imposed a near-absolute ban on discussion of the abortion option. This conventional wisdom, I conclude, collapses on careful inspection. It fails utterly to account for the strong support to be found in the Title X regulations and their larger legal context for a therapeutic exception unconstrained by administrative or judicial definition. Next, I observe that this legal unboundedness would have empowered Title X clinic physicians (and perhaps others who do counseling) to exercise broad discretion over abortion access, under the rubric of medical indication.... By so doing, however, physicians would have become abortion gatekeepers. This would have raised difficult ethical and clinical questions about the extent to which medical judgment should be allowed to incorporate (and shield) socially-disputed moral choices. I briefly consider some of these questions, along with the countervailing appeal of preserving a measure of intimate freedom under medical cover. I then conclude by positing some connections between the moral infirmities of medical gatekeeping and the political failure of the therapeutic exception. I suggest, in essence, that this failure was ensured by a strong resonance between the exception's moral infirmities and the fears of the medical leaders, pro-choice activists, and abortion opponents who framed the public debate over the "gag rule." The potential breadth of the therapeutic exception went unrecognized and unexplored because professional and popular understanding of the abortion counseling regulations was molded by the activists who framed the debate...


Perceived barriers to completing an e-learning program on evidence-based medicine.
The Continuing Professional Development Center of the Faculty of Medicine at Laval University offers an internet-based program on evidence-based medicine (EBM). After one year, only three physicians out of the 40 who willingly paid to register had completed the entire program. This descriptive study aimed to identify physicians' beliefs regarding their completion of this online program. Using theoretical concepts from the Theory of Planned Behaviour, a semi-structured telephone interview guide was developed to assess respondents' attitudes, perceived subjective norms, perceived obstacles and facilitating conditions with respect to completing this internet-based program. Three independent reviewers performed content analysis of the interview transcripts to obtain an appropriate level of reliability. Findings were shared and organised according to theoretical categories of beliefs. A total of 35 physicians (88% response rate) were interviewed. Despite perceived advantages to completing the internet-based program, barriers remained, especially those related to physicians' perceptions of time constraints. Lack of personal discipline and unfamiliarity with computers were also perceived as important barriers. This study offers a theoretical basis to understand physicians' beliefs towards completing an internet-based continuing medical education (CME) program on EBM. Based upon respondents' insights, several modifications were carried out to enhance the uptake of the program by physicians and, therefore, its implementation.


Arginine-facilitated isomerization: radical-induced dissociation of aliphatic radical cationic glycylarginyl(iso)leucine tripeptides.
The gas phase fragmentations of aliphatic radical cationic glycylglycyl(iso)leucine tripeptides ([G(•)G(L/I)](+)), with well-defined initial locations of the radical centers at their N-terminal α-carbon atoms, are significantly different from those of their basic glycylarginyl(iso)leucine ([G(•)R(L/I)](+)) counterparts; the former lead predominantly to [b(2) - H](•+) fragment ions, whereas the latter result in the formation of characteristic product ions via the losses of (•)CH(CH(3))(2) from [G(•)RL](+) and (•)CH(2)CH(3) from [G(•)RI](+) through C(β)-C(γ) side-chain cleavages of the (iso)leucine residues, making these two peptides distinguishable. The α-carbon-centered radical at the leucine residue is the key intermediate that triggers the subsequent C(β)-C(γ) bond cleavage, as supported by the absence of (•)CH(CH(3))(2) loss from the collision-induced dissociation of [G(•)RL(α-Me)](+), a radical cation for which the α-hydrogen atom of the leucine residue had been substituted by a methyl group. Density functional theory calculations at the B3LYP 6-31++G(d,p) level of theory supported the notion that the highly basic arginine residue could not only increase the energy barriers against charge-induced dissociation pathways but also decrease the energy barriers against hydrogen atom transfers in the GR(L/I) radical cations by ∼10 kcal mol(-1), thereby allowing the intermediate precursors containing α- and γ-carbon-centered radicals at the (iso)leucine residues to be formed more readily prior to promoting subsequent C(β)-C(γ) and C(α)-C(β) bond cleavages. The hydrogen atom transfer barriers for the α- and γ-carbon-centered GR(L/I) radical cations (roughly in the range 29-34 kcal mol(-1)) are comparable with those of the competitive side-chain cleavage processes. The transition structures for the elimination of (•)CH(CH(3))(2) and (•)CH(2)CH(3) from the (iso)leucine side chains possess similar structures, but slightly different dissociation barriers of 31.9 and 34.0 kcal mol(-1), respectively; the energy barriers for the elimination of the alkenes CH(2)═CH(CH(3))(2) and CH(3)CH═CHCH(3) through C(α)-C(β) bond cleavages of γ-carbon-centered radicals at the (iso)leucine side chains are 29.1 and 32.8 kcal mol(-1), respectively.


Stroke subtype, age, and baseline NIHSS score predict ischemic stroke outcomes at 3 months: a preliminary study from Central Nepal.
The combined medications practice of using antithrombotic agents and statins with or without antihypertensive agents is common in the treatment of acute ischemic stroke in Nepal. Short-term outcomes of the current practice have been studied. We aim to explore the predictors of ischemic stroke outcomes at 3 months, with the current combined medications practice. The study population (N=56) included acute ischemic stroke patients treated at the Neurology Department of the College of Medical Sciences-Teaching Hospital, Chitwan, Nepal, from May 2014 to August 2014 and followed up at 3 months. Death or disability (modified Rankin scale >2) was defined as poor outcomes. Multivariate logistic regression analysis (P<0.10) using potential variables from bivariate analysis (P≤0.20) was adjusted to predict outcomes at 3 months. At 3 months, 29 (51.8%) patients were independent, eleven (19.6%) were dependent, while 16 (28.6%) died. Stroke subtype and baseline National Institute of Health Stroke Scale (NIHSS) scores were associated with death/disability (27, 48.2%) at 3 months. Regression analysis showed that large-artery stroke (odds ratio [OR] =284.145, 95% confidence interval [CI] =5.221-15,465.136, P=0.006), age (OR =1.113, 95% CI =1.002-1.236, P=0.045), and baseline NIHSS score (OR =1.557, 95% CI =1.194-2.032, P=0.001) were significant predictors of poor outcome at 3 months. Stroke subtype, age, and baseline NIHSS score are predictors of ischemic stroke outcomes in Nepalese population treated with the current practice of using combined antithrombotic and statins with or without antihypertensive agents, and these predictors can be used for the improvement of selection of patients for the appropriate treatment.


The effect of early maternal maladaptation on fetal growth.
IUGR can develop, either in response to a reduced IGP or in response to a deficient transplacental supply of O2 and nutrients. Particularly, insight in the pathogenesis of extrinsic IUGR is important for the clinician to offer him tools for a more causal treatment. Extrinsic IUGR is usually preceded by a gradually developing uteroplacental insufficiency. Uteroplacental hypoperfusion may represent the common starting point for extrinsic IUGR and maternal systemic symptomatology (PIH, (pre)eclampsia). In addition, it may be the common endpoint of two different (subclinical) pathways: defective trophoblast differentiation ("primary") and decompensation of early-pregnancy circulatory maladaptation ("secondary"). From a theoretical point of view, the primary pathway may develop at a slower rate. Therefore, the primary pathway is more likely to result in extrinsic IUGR. In contrast, the secondary pathway assumes decompensation of an initially maladapted maternal circulation. This implies a highly variable rate of development and with it, severity of clinical symptomatology. It also indicates that the the pathogenesis, eventually leading to manifest vascular disease, is superimposed on a pre-existent inadequacy in maternal hemodynamics, renal function and/or volume homeostasis. It is understood that intertwining of these two pathways is common. Unfortunately, our current knowledge, about placentation and the concomitant early-pregnancy adjustments is poor. Current research of trophoblast differentiation and of the concomitant maternal end-organ effects in normal and pathologic pregnancy, is likely to increase our understanding of the first-trimester phenomena preceding IUGR soon.


An operation on placental support in a fetus with a nasopharyngeal teratoma.
Airway obstruction diagnosed antenatally in the fetus due to congenital high airway obstruction syndrome or nasopharyngeal masses are the primary indications for performing an operation on placental support. Prenatally diagnosed nasopharyngeal masses pose the risk of total airway obstruction upon delivery. Placental support utilises uteroplacental blood flow to facilitate an airway intervention on the fetus while maintaining oxygenation. These interventions must be completed in under 20 min due to amniotic fluid loss and uterine contractions. This case report describes the anaesthetic management of a fetus with a nasal teratoma. In this report, we discuss the clinical indications and anaesthetic considerations of the operation on placental support procedure for nasopharyngeal masses.


[The protective effect of alpha-2 adrenergic agonist on cranial nerve in rats with brain injury].
To investigate the neuroprotective effect of α2 adrenergic agonist, dexmedetomidine on tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) in brain tissue and serum S-100β protein level in traumatic brain injury rats. Seventy-two male Sprague-Dawley rats were randomly divided into sham operation group (group S), traumatic brain injury group (group C), and dexmedetomidine group (group D), 24 rats in each group; each of which was divided into 6, 12, 24 and 48 hours subgroup, 6 rats in each subgroup. Parietal brain contusion was produced by reformed Feeney method. The group S underwent sham operation without blunt force stroke; group D underwent blunt force stroke, then received loading dose of dexmedetomidine, 3 μg/kg with common jugular vein injection and continued infusion with 3 μg·kg(-1)·h(-1) for 2 hours. The total dosage of dexmedetomidine was 9 μg/kg with a volume of 4 ml; group C underwent 0.9% NaCl, 4 ml injection at the same time point with the same method. The S-100 protein activity in arteria cruralis serum was detected at the each time point by ELISA and TNF-α, IL-6 in the brain tissue were detected by ELISA. There were no significant difference of TNF-α activity among time point of 6, 12, 24 and 48 h in group S ((2.07±0.06), (2.01±0.03), (2.11±0.05), and (2.08±0.04) pg/mg, F=1.147, P>0.05), no significant difference of IL-6 activity among the same time point ((4.03±0.06), (4.07±0.09), (4.06±0.04), and (4.55±0.09) pg/mg, F=1.176, P>0.05), and no significant difference of serum S-100β activity among the same time too ((0.37±0.07), (0.36±0.02), (0.35±0.06), and (0.39±0.11) μg/L, F=1.045, P>0.05). The above indexes in group C were higher than those in group S, and the above indexes in group D were higher than those in group S and lower than those in group C (all P<0.05). Alpha-2 adrenergic agonist, dexmedetomidine could dramatically inhibit inflammatory reaction induced by traumatic brain injury in rats and protect brain tissue.


Biological effects of leptospiral lipids.
Lipids were extracted from virulent Leptospira pomona and were purified. These lipids fixed complement in the presence of antiserum to L. pomona but did not stimulate the production of homologous agglutinins in rabbits, mice, or hamsters. When subsequently challenged, all of the mice and hamsters were fully susceptible to L. pomona. The lipid material was neither dermonecrotic nor lethal for mice or hamsters, but 382 mug of lipid from virulent or avirulent leptospires inhibited the growth of normal mice. Leptospiral lipids were toxic for peritoneal macrophages maintained in vitro, and when administered simultaneously with a million lethal doses of L. pomona, the lipids hastened death of the hamsters, presumably by inhibiting phagocytosis early in the course of the infection.


Testing the equivalence of the socialization factor structure for criminals and noncriminals.
Considerable evidence supports the criterion-related validity of the Socialization (So) scale of the California Psychological Inventory (Gough, 1948, 1994, 1996) for the prediction of antisocial and prosocial behavior. However, no research has examined the similarity of the So construct for the two populations. Meaningful interpretation of So scores is possible if the factor structure is equivalent for antisocial and prosocial groups.


Robust plan optimization using edge-enhanced intensity for intrafraction organ deformation in prostate intensity-modulated radiation therapy.
This study evaluated a method for prostate intensity-modulated radiation therapy (IMRT) based on edge-enhanced (EE) intensity in the presence of intrafraction organ deformation using the data of 37 patients treated with step-and-shoot IMRT. On the assumption that the patient setup error was already accounted for by image guidance, only organ deformation over the treatment course was considered. Once the clinical target volume (CTV), rectum, and bladder were delineated and assigned dose constraints for dose optimization, each voxel in the CTV derived from the DICOM RT-dose grid could have a stochastic dose from the different voxel location according to the probability density function as an organ deformation. The stochastic dose for the CTV was calculated as the mean dose at the location through changing the voxel location randomly 1000 times. In the EE approach, the underdose region in the CTV was delineated and optimized with higher dose constraints that resulted in an edge-enhanced intensity beam to the CTV. This was compared to a planning target volume (PTV) margin (PM) approach in which a CTV to PTV margin equivalent to the magnitude of organ deformation was added to obtain an optimized dose distribution. The total monitor units, number of segments, and conformity index were compared between the two approaches, and the dose based on the organ deformation of the CTV, rectum, and bladder was evaluated. The total monitor units, number of segments, and conformity index were significantly lower with the EE approach than with the PM approach, while maintaining the dose coverage to the CTV with organ deformation. The dose to the rectum and bladder were significantly reduced in the EE approach compared with the PM approach. We conclude that the EE approach is superior to the PM with regard to intrafraction organ deformation.


[Ventricular arrhythmias in patients with aortic valve disease (author's transl)].
In order to investigate the incidence of severe ventricular arrhythmias, the 24-h ambulatory ECG of 55 patients with aortic valve disease (NYHA classes I-IV; stenosis: n = 24; regurgitation: n = 18; mixed lesions: n = 13) without coronary heart disease were evaluated with regard to the number of premature ventricular beats and according to the Lown classification. Ventricular arrhythmias were found in 73% of all patients (Lown classes III-V: 38%; Lown classes IV-V: 20%). A significant relation between the degree of arrhythmias and the gradient or severity of regurgitation of the aortic valve could not be established. However, there was a significant linear correlation between the left ventricular ejection fraction and the degree of arrhythmias (stenosis: r = 0.60; regurgitation: r = -0.72; mixed lesions: r = 0.78; all p less than 0.005). Complex arrhythmias of Lown classes III-IV are rare (less than 10%) in patients with good left ventricular function (LVEF greater than 60%). There was a history of palpitations in 81% of patients with Lown classes III-V. According to these data, ventricular arrhythmias are present in a large number of patients with aortic valve disease. The degree of arrhythmia does not correlate to the transvalvular stenosis or the severity of regurgitation, but is strongly influenced by the myocardial performance. Therefore in patients with aortic valve disease significant arrhythmias are frequently a sign of impaired LV function.


Effect of weight loss with or without orlistat treatment on adipocytokines, inflammation, and oxidative markers in obese women.
The aim of this study was to evaluate the levels of adipose tissue related hormones, cytokines, and antioxidative substances in obese women before and after intervention with diet alone or with diet plus an inhibitor of gastrointestinental lipase-orlistat. Seventy-one obese women of childbearing age were included in the study and were randomly assigned into two groups according to the type of intervention: group A1 (n=35) included women who received orlistat as well as a hypocaloric diet, and group A2 (n=36) included women who were only on hypocaloric diet. The intervention period lasted 6 months. Anthropometric parameters, such as Body Weight (BW), Body Mass Index (BMI), Waist Circumference (WC), and %Body fat (BF) were recorded. Insulin, leptin, resistin, interleukin-6 (IL-6), insulin like growth factor 1 (IGF-1), tumor necrosis factor alpha (TNFalpha), adiponectin, hsC-reactive protein (CRP), glutathione peroxidase, and isoprostane were determined by appropriate methodology prior to and following the 6-month intervention period. Insulin resistance was measured using the homeostasis model assessment index (HOMA-IR). All participants had normal glucose tolerance. In both groups B MI values were lower after intervention and all measured parameters were ameliorated. A statistically significant difference was found between group A1 (orlistat plus diet) and group A2 (diet only) with regard to the levels of triglycerides, CRP, TNF-alpha, IGF-1, and isoprostane, even after correcting for weight loss. Hypocaloric diet plus orlistat in obese women is superior to diet alone with regard to the changes observed in adipokines, CRP, TNFalpha, triglycerides, IGF-1, and oxidative stress following intervention.


Comparative docking analysis of tyrosine kinase inhibitors with HER2 and HER4 receptors.
Tyrosine kinase receptors promote the growth and differentiation of normal breast and malignant human breast cancer cells, known as ERBB receptors. Various ERBB receptors are EGFR/ErbB1 and ErbB2/neu, which get over expressed in different solid tumors that activate upon binding of ligand to the extra cellular domain of these receptors. Of note, the epidermal growth factor receptor (EGFR) is a prime contributor to cancer through the involvement of four receptor tyrosine kinases (RTKs), namely, HER1, HER2, HER3, and HER4. Among them, HER2 and HER4 are majorly associated with breast cancer. Non-peptide quinazoline compounds homologous of the adenosine triphosphate (ATP) are competitively inhibited to RTKs to prevent cancer growth and metastasis. Various small drug molecule that targets the RTKs having the same scaffold, includes Lapatinib, Tivozanib, Erlotinib, Gefitinib, Crizotinib, and Ceritinib. The present study aims to investigate the comparative potential of structurally similar TKIs against HER2 and HER4 receptor receptors-silico molecular docking using FlexX software (LeadIT 2.3.2). Each docked complex's interaction profile was performed using BIOVIA Discovery Studio Visualizer 4.0. Molecular docking analysis was performed in order to get deeper insights into the interaction and binding pattern of the ligands with HER2 and HER4 receptors. The docking results revealed the Lapatinib compound acquired the relatively highest binding score of -32.36 kcal/mol and -35.76 kcal/mol with HER2 and HER4 proteins, respectively, concerning other compounds. Lapatinib is identified as a potential inhibitor for both the RTKs. Our study thus suggests the probable direction that could be further explored in inhibiting EGFR protein harboring breast cancer.


Dihydrotestosterone receptors in the human prostate. I. Nuclear concentration in normal, benign, and malignant tissues.
A technique was standardized to measure nuclear dihydrotestosterone receptors in human prostate. Normal, hyperplastic (BPH), and cancer tissues were homogenized and the homogenate centrifuged at 600 g X 10 min; the pellet was purified on sucrose density gradient. Purified nuclei were extracted with 0.4 M KC1. The nuclear extract was then incubated in the presence of [3H]dihydrostestosterone (DHT) at 4 degrees C for 20 hr. Competition studies with different steroids indicated a high specificity of the receptor towards DHT and no affinity towards progesterone and 17 beta-estradiol. Isolation and purification of [3H]DHT after its incubation in the presence of the KC1 nuclear extract indicated that no significant degradation of the hormone occurred during incubation. The number of binding sites measured was 8.5 +/- 0.77 fmol/mg protein (mean +/- SEM) for normal, 38.6 +/- 5.9 for BPH, and 79.9 +/- 21.9 for cancer. The possible clinical application of these results will require a long-term follow-up of the hormonal responsiveness of the prostatic-cancer patients investigated.


Lesions induced by 2,4-D and chlorpyrifos in tench (Tinca tinca L.): implication in toxicity studies.
This study was undertaken to demonstrate the toxicity of two pesticides, chlorpyrifos (O,O-diethyl 0-3,5,6-trichloro-2-pyridyl phosphorothioate) and 2,4-D (Dichlorophenoxyacetic acid) to tench (Tinca tinca Linnaeus). Pathological samples of damaged tench kidney showing lesions were taken for statistical analysis in order to quantify different parameters. Analysis revealed differences in the action and/or action time of the two pesticides. These differences were more acute in the case of 2,4-D thereby indicating a greater toxicity. These differences, expressed by mathematical formulae of numerical variables, would enable, a priori, the identification of the responsible pesticide and the time of acting in new natural cases of poisonings with these substances.