Experimental study of cryofreezing energy applications on the ventricular myocardium using sheep hearts.
Cryofreezing energy has been utilized to abolish arrhythmogenic substrates of various kinds of tachyarrhythmias. However, systematic electrophysiological and histological investigations of cryothermia have never been performed. The aim of this study was to clarify those aspects using sheep beating hearts. A total of eight adult sheep were utilized under total anesthesia, and a pericardial cradle was made by opening the pericardium. Eight epicardial plaque electrodes were sutured on the epicardial surface of the left ventricle 2∼3 cm apart from each other. A cryoprobe was inserted through a vent made in the left ventricular apex, and positioned so as to locate the probe tip at a site just opposite the center of the epicardial plaque electrodes. Ventricular electrograms and pacing threshold were measured during endocardial freezing. The volume of the necrotized lesion created by the cryofreezing was measured in the excised hearts after staining. The cryoprobe tip temperature was lowered to -50°C for 10 minutes. A significant increase in the pacing threshold and significant reduction in the ventricular electrograms were observed after endocardial freezing. The transmurality of the necrotized lesions varied depending on the situation of the cryoapplications, and the lesion depth and volume were significantly larger in the transmural lesions; however, there was no significant difference between the transmural and nontransmural lesions regarding the lesion width. Endocardial cryofreezing could provoke significant electrophysiological and injurious effects on the ventricular myocardium in the goat heart. Transmural cryolesions could be created when cryoprobe was appropriately applied.


Update on prevention of malaria for travelers.
Individuals from industrialized nations frequently travel to countries with malaria, so health care providers need to be familiar with current recommendations for prevention of malaria. Changes in drug susceptibility of malaria parasites and evolving knowledge of how well drugs are tolerated necessitate periodic review of guidelines for prophylaxis of malaria, especially of chloroquine-resistant Plasmodium falciparum malaria. Mefloquine is the drug of choice for chemoprophylaxis for most travelers, with doxycycline and chloroquine being less effective alternatives. Mefloquine is well tolerated at prophylactic dosages, but anecdotal reports have raised concerns about its adverse effects. Resistance to this drug has emerged in parts of Southeast Asia and may spread to other regions of the world. The major disadvantages of doxycycline are the need for daily dosing, its contraindication for young children and pregnant women, and its adverse effects. Chloroquine is effective for prophylaxis only in Central America, the Caribbean, and parts of the Middle East. Few new drugs will be available in the near future because of reduced funding for antimalarial drug research and development; therefore, the usefulness of currently available drugs needs to be prolonged by rational use. Increased efforts should be made to ensure that alternative drugs will be available for prevention of malaria.


Hemostatic capability of ultrafiltrated fresh frozen plasma compared to cryoprecipitate.
This in vitro study evaluated the potential hemostatic effect of fresh frozen plasma (FFP) ultrafiltration on clotting factors, coagulation parameters, and plasma properties. ABO-specific units of FFP (n = 40) were prepared for the concentrated FFP and cryoprecipitate. Plasma water was removed from FFP by ultrafiltration using a dialyzer with a pump running at a 300 mL/min. The aliquot of each concentrated FFP after 50, 100, 200, and 250 mL of fluid removal were measured the standard coagulation assay, clotting activity, and plasma properties to compare those parameters of cryoprecipitate. Concentrated FFP contained 36.5% of fibrinogen in FFP with a mean concentration of 7.2 g/L, lower than the cryoprecipitate level. The levels of factor VIII (FVIII), von Willebrand factor (VWF):antigen (Ag), and VWF:ristocetin cofactor (RCo) were also lower in concentrated FFP, whereas the levels of factor V, factor IX, factor XIII, antithrombin and albumin was higher in concentrated FFP. Maximum clot firmness (MCF) in thromboelastometry was approximately one-half of that in cryoprecipitate. Although the levels of VWF:Ag, VWF:RCo, and FVIII differed depending on the ABO blood types, fibrinogen levels, and MCF were not significantly different among the ABO blood groups in FFP and concentrated FFP.


Prolonged conservative treatment or 'early' surgery in sciatica caused by a lumbar disc herniation: rationale and design of a randomized trial [ISRCT 26872154].
The design of a randomized multicenter trial is presented on the effectiveness of a prolonged conservative treatment strategy compared with surgery in patients with persisting intense sciatica (lumbosacral radicular syndrome). Patients presenting themselves to their general practitioner with disabling sciatica lasting less than twelve weeks are referred to the neurology outpatient department of one of the participating hospitals. After confirmation of the diagnosis and surgical indication MRI scanning is performed. If a distinct disc herniation is discerned which in addition covers the clinically expected site the patient is eligible for randomization. Depending on the outcome of the randomization scheme the patient will either be submitted to prolonged conservative care or surgery. Surgery will be carried out according to the guidelines and between six and twelve weeks after onset of complaints. The experimental therapy consists of a prolonged conservative treatment under supervision of the general practitioner, which may be followed by surgical intervention in case of persisting or progressive disability. The main primary outcome measure is the disease specific disability of daily functioning. Other primary outcome measures are perceived recovery and intensity of legpain. Secondary outcome measures encompass severity of complaints, quality of life, medical consumption, absenteeism, costs and preference. The main research question will be answered at 12 months after randomization. The total follow-up period covers two years. Evidence is lacking concerning the optimal treatment of lumbar disc induced sciatica. This pragmatic randomized trial, focusses on the 'timing' of intervention, and will contribute to the decision of the general practictioner and neurologist, regarding referral of patients for surgery.


Assessing depression in prepubertal children.
Although symptoms of major depression are the same in adults and prepubertal children, diagnosing depression in children presents special problems not encountered with adults. In addition to the standard clinical interview, methods of assessing childhood depression include diagnostic interviews, self-report inventories, projective tests, peer ratings, and biological markers. Unfortunately many of these methods currently lack detailed reliability and validity studies. Despite their limitations these techniques can be helpful in making a diagnosis. However, accurate diagnosis still requires careful evaluation and individualized clinical judgement.


Racial disparities in age at time of cardiovascular events and cardiovascular-related death in patients with systemic lupus erythematosus.
To determine whether racial disparities exist with regard to the age at which patients with systemic lupus erythematosus (SLE) experience cardiovascular disease (CVD) and CVD-associated death. Using the 2003-2006 Nationwide Inpatient Sample, we calculated the age difference between patients with SLE and their race- and sex-matched controls at the time of hospitalization for a cardiovascular event and for CVD-associated death. In addition, we calculated the age difference between white patients with SLE and sex-matched controls for each minority group for the same outcomes. The mean age difference between women with and those without SLE at the time of admission for a CVD event was 10.5 years. All age differences between women with SLE (n = 3,627) and women without SLE admitted for CVD were significant (P < 0.0001). Among different racial groups with SLE, black women were the youngest to be admitted with CVD (53.9 years) and to have a CVD-associated in-hospital death (52.8 years; n = 218). Black women with SLE were 19.8 years younger than race- and sex-matched controls at the time of CVD-associated death. Admission trends for CVD were reversed for black women, such that the highest proportions of these patients were admitted before age 55 years, and then the proportions steadily decreased across age categories. Among the 805 men with SLE who were admitted with a CVD event, those who were black or Hispanic were youngest. There are significant racial disparities with regard to age at the time of hospital admission for CVD events and CVD-related hospitalization resulting in death in patients with SLE.


A Risk Assessment Matrix for Public Health Principles: The Case for E-Cigarettes.
Besides nicotine replacement therapies, a realistic alternative for smoking cessation or for smoking substitution may come from electronic cigarettes (ECs), whose popularity has been steadily growing. As for any emerging behaviour associated with exposure to inhalational agents, there is legitimate cause for concern and many health organizations and policy makers have pushed for restrictive policy measures ranging from complete bans to tight regulations of these products. Nonetheless, it is important to reframe these concerns in context of the well-known harm caused by cigarette smoking. In this article, we discuss key public health principles that should be considered when regulating ECs. These include the concept of tobacco harm reduction, importance of relative risk and risk continuum, renormalization of smoking, availability of low-risk product, proportionate taxation, and reassessment of the role of non-tobacco flavours. These public health principles may be systematically scrutinized using a risk assessment matrix that allows: (1) to determine the measure of certainty that a risk will occur; and (2) to estimate the impact of such a risk on public health. Consequently, the ultimate goal of responsible ECs regulation should be that of maximizing the favourable impact of these reduced-risk products whilst minimizing further any potential risks. Consumer perspectives, sound EC research, continuous post-marketing surveillance and reasonable safety and quality product standards should be at the very heart of future regulatory schemes that will address concerns while minimizing unintended consequences of ill-informed regulation.


Fenugreek (Trigonella foenum-graecum L.) as an alternative forage for dairy cows.
Fenugreek is a novel forage crop in Canada that is generating interest as an alternative to alfalfa for dairy cows. To evaluate the value of fenugreek haylage relative to alfalfa haylage, six, second lactation Holstein cows (56 ± 8 days in milk), which were fitted with rumen cannulas (10 cm i.d., Bar Diamond Inc., Parma, ID, USA) were used in a replicated three × three Latin square design with 18-day periods. Diets consisting of 400 g/kg haylage, 100 g/kg barley silage and 500 g/kg concentrate on a dry matter (DM) basis were fed once daily for ad libitum intake. The haylage component constituted the dietary treatments: (i) Agriculture and Agri-Food Canada F70 fenugreek (F70), (ii) Crop Development Center Quatro fenugreek (QUAT) and (iii) alfalfa (ALF). DM intake (DMI), milk yield and milk protein and lactose yields were higher (P < 0.001) for cows fed ALF than fenugreek (FEN, average of F70 and QUAT). Milk fat of cows fed FEN contained lower concentrations of saturated, medium-chain and hypercholestrolemic fatty acids (FAs; P < 0.05) than that of cows fed ALF. Apparent total tract digestibility of DM and nutrients was not affected by treatments. Similarly, individual ruminal volatile FA concentrations and rumen pH (5.9) were not affected by treatments. Rumen ammonia-N concentration was higher for FEN than ALF (P < 0.001). Estimates of neutral detergent fiber (NDF) passage rate (P < 0.05) and NDF turnover rate (P < 0.001) in the rumen were higher for ALF than FEN. Our results suggest that although the digestibility of the FEN diets was not different from that of the ALF diet, fenugreek haylage has a lower feeding value than ALF for lactating dairy cows due in part to lower DMI and subsequently lower milk yield.


Delayed-onset postoperative endophthalmitis secondary to Exophiala.
Exophiala is a genus of slow-growing, melanin-producing, saprophytic fungi most commonly found in soil, faeces and decaying plant matter. It is an unusual fungal pathogen capable of causing a variety of ophthalmic manifestations, including keratitis, scleritis and endophthalmitis. In this report, we present a rare case of delayed-onset postoperative endophthalmitis confined to the anterior segment, secondary to Exophiala species. Previous reported cases of delayed-onset postoperative endophthalmitis have been treated medically, with suboptimal outcomes. Our experience supports the use of anterior segment surgery to clear the nidus of disease combined with intravitreal voriconazole to prevent recurrence of the infection.


Resistance of mice to infection with Friend disease virus after subcutaneous injection of Friend virus and Friend spleen cells.
Swiss mice injected subcutaneously with suspensions of spleen cells or an extract of spleens from mice infected with Friend virus develop resistance to subsequent intravenous inoculation of Friend virus. A single injection of either Friend virus or Friend cells induces resistance. Immunized mice display resistance when challenged 6 months after immunization and survive for at least 20 weeks after infection. Neutralization tests indicate that serum, but not lymphoid cells of resistant animals, can neutralize Friend virus. In vitro neutralization tests indicate that residence of virus within the peritoneal cavity of immune mice for 1 h sharply reduces the infective titer of the virus.


Myasthenia graves-like symptoms associated with rare mitochondrial mutation (m.5728T>C).
We report here on a patient who presented with myasthenia gravis type symptoms (fatigable ptosis, increased jitter on single fiber EMG, and a thymic mass) who was subsequently diagnosed with a mitochondrial myopathy. Sequencing of the mitochondrial genome (mtDNA) identified a transition variant in the tRNA asparagine gene (MT-TN) (m.5728T>C) at in 41% of mtDNA molecules in muscle tissue. The variant was not detectable in blood. The m.5728T>C variant has been reported previously in a ten year old male with global developmental delays, failure to thrive, ataxia, weakness, cognitive regression, seizures, and glomerulosclerosis. The variant was seen in 97% of mtDNA molecules in muscle and 50% in blood. This case report supports the pathogenicity of the m.5728T>C and helps to establish the phenotypic spectrum of this condition at a lower heteroplasmy.


Delayed cataract formation after alkali burn.
A small posterior subcapsular cataract developed almost a year after a moderately severe alkali burn of the eye. The cornea recovered completely. Cataract and glaucoma following alkali burns are discussed. The development of delayed cataract should be kept in mind in compensation cases before a final disability report is made. Topical steroids may potentiate the detrimental effect of alkali on the eye.


SLIM microscopy allows for visualization of DNA-containing liposomes designed for sperm-mediated gene transfer in cattle.
Naked DNA has been shown to bind naturally to the sperm, a method called sperm-mediated gene transfer (SMGT). Based on these observations, we examined the efficiency of exogenous DNA binding to sperm using liposomes. In this experiment, we analyzed methods to select frozen-thawed bovine sperm, and evaluated the binding of exogenous DNA to those sperm. To determine the optimal selection method, we used Computer-Assisted Sperm Analysis (CASA). Percoll or Swim-Up were used to select sperm, followed by incubation up to 3 h with the liposome-DNA complexes. The samples were collected after 1 h and after 3 h. We used enhanced green fluorescent protein (eGFP) in combination with the liposomes as a marker for exogenous DNA binding. Five treatments per selection method were analyzed: (1) no incubation, no liposomes and no DNA, (2) incubation with no liposomes and no DNA, (3) incubation with liposomes and no DNA, (4) incubation with liposomes and 1 µg of DNA and (5) incubation with liposomes and 10 µg of DNA. The CASA results for total motility and rapid motility were statistically significant (P < 0.01) between the control and the other treatments in the Percoll group as opposed to Swim-Up. Swim-Up was therefore chosen as the optimal selection method. In order to determine if the liposome-DNA complex had bound to sperm, real time PCR was used to detect GFP DNA and images of the sperm were analyzed using the Spatial Light Interference Microscopy (SLIM). SLIM confirmed the presence of liposomes on the sperm head and tail.


Automated structure discovery in atomic force microscopy.
Atomic force microscopy (AFM) with molecule-functionalized tips has emerged as the primary experimental technique for probing the atomic structure of organic molecules on surfaces. Most experiments have been limited to nearly planar aromatic molecules due to difficulties with interpretation of highly distorted AFM images originating from nonplanar molecules. Here, we develop a deep learning infrastructure that matches a set of AFM images with a unique descriptor characterizing the molecular configuration, allowing us to predict the molecular structure directly. We apply this methodology to resolve several distinct adsorption configurations of 1S-camphor on Cu(111) based on low-temperature AFM measurements. This approach will open the door to applying high-resolution AFM to a large variety of systems, for which routine atomic and chemical structural resolution on the level of individual objects/molecules would be a major breakthrough.


Sequential Nucleophilic "Click" Reactions for Functional Amphiphilic Homopolymers.
Amphiphilic homopolymers with high densities of functional groups are synthetically challenging. Thiol-yne nucleophilic click reactions have been investigated to introduce multiple functional groups in polymers with high density. An electron deficient alkyne group bearing methacrylate monomer was polymerized using reversible addition-fragmentation chain-transfer (RAFT) polymerization. Subsequently, the electron deficient alkyne group on polymer side chain was readily reacted with a thiol reagent using triethylamine (TEA) as the organocatalyst. This reaction was found to be very efficient under mild conditions. The resultant homopolymer bearing thiol vinyl ether functional groups could perform a second thiol addition with a stronger base, such as triazabicyclodecene (TBD), to prepare multifunctional homopolymers. This stepwise addition process was monitored by 1H NMR as well as gel permeation chromatography. The fidelity of this method was demonstrated by attaching four different functionalities, including both hydrophobic and hydrophilic moieties. Furthermore, these dual functionalized polymers bearing dithio-acetal groups are sensitive to reactive oxygen species (ROS), which compromises the host-guest properties of the assembly in response to this stimulus. The ROS responsive polymers reported here may have potential use in therapeutic delivery.


Reevaluation of the accepted allosteric mechanism of phosphofructokinase from Bacillus stearothermophilus.
The binding of phosphoenolpyruvate (PEP) to the single allosteric site on phosphofructokinase (EC ) from Bacillus stearothermophilus (BsPFK) diminishes the ability of the enzyme to bind the substrate fructose 6-phosphate (Fru-6-P). Comparisons of crystal structures with either Fru-6-P or phosphoglycolate, an analog of PEP, bound have shown that Arg-162 interacts with the negatively charged Fru-6-P. Upon the binding of phosphoglycolate, Arg-162 is virtually replaced by Glu-161, which introduces a potential coulombic repulsion between enzyme and substrate [Schirmer, T. & Evans, P. R. (1990) Nature (London) 343, 140-145]. It has previously been proposed that this structural transition explains the allosteric inhibition in BsPFK, and this explanation has appeared in textbooks to illustrate how an allosteric ligand can influence substrate binding at a distance. Site-directed mutagenesis has been employed to create three mutants of BsPFK that substitute an alanine residue for Glu-161, Arg-162, or both. The E161A mutation does not affect the inhibition of BsPFK by PEP at 25 degrees C, and while the R162A mutation decreases BsPFK's affinity for Fru-6-P by approximately 30-fold, R162A diminishes the effectiveness of PEP inhibition by only 1/3. Combining E161A and R162A produces behavior comparable to R162A alone. These and other data suggest that the movement of Glu-161 and Arg-162 does not play the central role in producing the allosteric inhibition by PEP as originally envisioned in the Schirmer and Evans mechanism.


The carbohydrate-binding specificity and molecular modelling of Canavalia maritima and Dioclea grandiflora lectins.
The carbohydrate-binding specificity of lectins from the seeds of Canavalia maritima and Dioclea grandiflora was studied by hapten-inhibition of haemagglutination using various sugars and sugar derivatives as inhibitors, including N-acetylneuraminic acid and N-acetylmuramic acid. Despite some discrepancies, both lectins exhibited a very similar carbohydrate-binding specificity as previously reported for other lectins from Diocleinae (tribe Phaseoleae, sub-tribe Diocleinae). Accordingly, both lectins exhibited almost identical hydropathic profiles and their three-dimensional models built up from the atomic coordinates of ConA looked very similar. However, docking experiments of glucose and mannose in their monosaccharide-binding sites, by comparison with the ConA-mannose complex used as a model, revealed conformational changes in side chains of the amino acid residues involved in the binding of monosaccharides. These results fully agree with crystallographic data showing that binding of specific ligands to ConA requires conformational chances of its monosaccharide-binding site.


Imaging technique implemented in CellTracks system.
We developed the CellTracks cell analysis system that, similar to flow cytometry, yields multiparameter information by which the cells can be differentiated. We describe the implementation of a laser scanning imaging method in the system. Image analysis of the cells improves the specificity of cell classification, especially in cases where the particular cells are found relatively infrequently and one has to discriminate between artifacts and real events. Fluorescent images of immunomagnetically labeled and aligned cells are obtained by passing the cells through a laser focus. The laser focus is smaller than the objects and subsequent frames captured by a regular surveillance CCD camera with a frame grabber board represent different parts of the cells. Complete images of the cells are constructed by shifting each image with respect to each other and adding individual pixel values. The power of combining a fluorescent image with multiparametric data is demonstrated by imaging fluorescent and magnetically labeled beads and cells. The image gives additional information about the dye distribution across the objects. Changes in dye distribution as a function of time were observed in leukocytes labeled with the red fluorescent label, Oxazine750, which are imaged at different time intervals. An imaging technique implemented in the CellTracks system provides high-resolution fluorescent images of events previously identified by the system. The images of the fluorescent cells enhance the ability to classify rare events.


Acute bacterial rhinosinusitis in adults: part II. Treatment.
Although most cases of acute rhinosinusitis are caused by viruses, acute bacterial rhinosinusitis is a fairly common complication. Even though most patients with acute rhinosinusitis recover promptly without it, antibiotic therapy should be considered in patients with prolonged or more severe symptoms. To avoid the emergence and spread of antibiotic-resistant bacteria, narrow-spectrum antibiotics such as amoxicillin should be used for 10 to 14 days. In patients with mild disease who have beta-lactam allergy, trimethoprim/sulfamethoxazole or doxycycline are options. Second-line antibiotics should be considered if the patient has moderate disease, recent antibiotic use (past six weeks), or no response to treatment within 72 hours. Amoxicillin-clavulanate potassium and fluoroquinolones have the best coverage for Haemophilus influenzae and Streptococcus pneumoniae. In patients with beta-lactam hypersensitivity who have moderate disease, a fluoroquinolone should be prescribed. The evidence supporting the use of ancillary treatments is limited. Decongestants often are recommended, and there is some evidence to support their use, although topical decongestants should not be used for more than three days to avoid rebound congestion. Topical ipratropium and the sedating antihistamines have anticholinergic effects that maybe beneficial, but there are no clinical studies supporting this possibility. Nasal irrigation with hypertonic and normal saline has been beneficial in chronic sinusitis and has no serious adverse effects. Nasal corticosteroids also may be beneficial in treating chronic sinusitis. Mist, zinc salt lozenges, echinacea extract, and vitamin C have no proven benefit in the treatment of acute bacterial rhinosinusitis.


Filimonas zeae sp. nov., an endophytic bacterium isolated from maize root.
A novel Gram-stain-negative, aerobic, motile by gliding and filamentous strain, designated 772T,was isolated from surface-sterilized root tissue of maize planted in the Fangshan District of Beijing, China. 16S rRNA gene sequence analysis indicated that strain 772T was closely related to Filimonas endophytica SR2-06T andFilimonas lacunae YT21T of the family Chitinophagaceae with sequence similarities of 99.0 and 96.9 %, respectively. However, the new isolate exhibited relatively low levels of DNA-DNA relatedness with respect to Filimonas. endophytica KCTC 42060T (18.7±1.8 %) and Filimonas. lacunae DSM 21054T (17.9±2.0%). The DNA G+C content of strain 772T was 44.9 mol%. The respiratory quinone was menaquinone-7 and the polar lipid profile consisted of phosphatidylethanolamine, two unidentified aminophospholipids, two unidentified phospholipids and one unidentified lipid. The major fatty acids were iso-C15 : 0 and iso-C15 : 1 G. The results of the physiological and biochemical tests and minor differences in the fatty acid profiles allowed the clear phenotypic differentiation of strain 772T from the closely related species Filimonas. endophytica andF. lacunae. Strain 772T thus represents a novel species within the genus Filimonas, for which the name Filimonas zeae sp. nov. is proposed. The type strain is 772T (=CGMCC 1.15290T=DSM 100760T).


Effects of Boundaries on Pattern Formation: Catalytic Oxidation of CO on Platinum.
The effect of boundaries on pattern formation was studied for the catalytic oxidation of carbon monoxide on platinum surfaces. Photolithography was used to create microscopic reacting domains on polycrystalline foils and single-crystal platinum (110) surfaces with inert titanium overlayers. Certain domain geometries give rise to patterns that have not been observed on the untreated catalyst and bring to light surface mechanisms that have no analog in homogeneous reaction-diffusion systems.


Probing the Sulfur-Modified Capping Layer of Gold Nanoparticles Using Surface Enhanced Raman Spectroscopy (SERS) Effects.
Gold nanoparticles (AuNP) exhibit particular plasmonic properties when stimulated by visible light, which makes them a promising tool to many applications in sensor technology and biomedical applications, especially when associated to sulfur-based compounds. Sulfur species form a great variety of self-assembled structures that cap AuNP and this interaction rules the optical and plasmonic properties of the system. Here, we report the behavior of citrate-stabilized gold nanospheres in two distinct sulfur colloidal solutions, namely, thiocyanate and sulfide ionic solutions. Citrate-capped gold nanospheres were characterized using ultraviolet-visible (UV-Vis) absorption, transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), and atomic force microscopy (AFM). In the presence of sulfur species, we have observed the formation of NP clusters and chain-like structures, giving rise to surface-enhanced effects. Surface-enhanced Raman spectroscopy (SERS) pointed to a modification in citrate vibrational modes, which suggests substitution of citrate by either thiocyanate or sulfide ions with distinct dynamics, as showed by in situ fluorescence. Moreover, we report the emergence of surface-enhanced infrared absorption (SEIRA) effect, which corroborates SERS conclusions. Further, SEIRA shows a great potential as a tool for specification of sulfur compounds in colloidal solutions, which is particularly useful when dealing with sensor technology.


Combined analyses of kinship and FST suggest potential drivers of chaotic genetic patchiness in high gene-flow populations.
We combine kinship estimates with traditional F-statistics to explain contemporary drivers of population genetic differentiation despite high gene flow. We investigate range-wide population genetic structure of the California spiny (or red rock) lobster (Panulirus interruptus) and find slight, but significant global population differentiation in mtDNA (ΦST = 0.006, P = 0.001; D(est_Chao) = 0.025) and seven nuclear microsatellites (F(ST) = 0.004, P < 0.001; D(est_Chao) = 0.03), despite the species' 240- to 330-day pelagic larval duration. Significant population structure does not correlate with distance between sampling locations, and pairwise FST between adjacent sites often exceeds that among geographically distant locations. This result would typically be interpreted as unexplainable, chaotic genetic patchiness. However, kinship levels differ significantly among sites (pseudo-F(16,988) = 1.39, P = 0.001), and ten of 17 sample sites have significantly greater numbers of kin than expected by chance (P < 0.05). Moreover, a higher proportion of kin within sites strongly correlates with greater genetic differentiation among sites (D(est_Chao), R(2) = 0.66, P < 0.005). Sites with elevated mean kinship were geographically proximate to regions of high upwelling intensity (R(2) = 0.41, P = 0.0009). These results indicate that P. interruptus does not maintain a single homogenous population, despite extreme dispersal potential. Instead, these lobsters appear to either have substantial localized recruitment or maintain planktonic larval cohesiveness whereby siblings more likely settle together than disperse across sites. More broadly, our results contribute to a growing number of studies showing that low F(ST) and high family structure across populations can coexist, illuminating the foundations of cryptic genetic patterns and the nature of marine dispersal.


Apigetrin treatment attenuates LPS-induced acute otitis media though suppressing inflammation and oxidative stress.
The natural course of otitis media in children is acute and self-limiting. Nevertheless, about 10-20% children could experience recurrent or persistent otitis media. Thus, finding effective candidate to prevent acute otitis media is urgently required. In our study, mouse acute otitis media model was constructed by lipopolysaccharide (LPS) injection into the middle ear of mice via the tympanic membrane. Apigetrin (APT) is a flavonoid isolated from various herbal medicines, possessing anti-inflammatory and anti-oxidative bioactivities. However, if APT could attenuate acute otitis media in LPS-induced animal models, little is to be known. Hematoxylin and eosin (H&E) staining suggested that APT treatment reduced LPS-induced higher mucosa thickness. LPS-triggered inflammatory response was also inhibited by APT, as evidenced by the down-regulated neutrophils and macrophages. Additionally, the reduced inflammatory factors, including interleukin-1β (IL-lβ), tumor necrosis factor α (TNF-α), IL-6 and vascular endothelial growth factor (VEGF) were observed in APT-treated mice with acute otitis media. The process was associated with the inhibition of toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathway, which was proved by the blockage of TLR4, MyD88, p-IKKα, p-IκBα, and p-NF-κB using western blot analysis. Moreover, the production of reactive oxygen species (ROS) caused by LPS was also reduced by APT through promoting anti-oxidants, involving superoxide dismutase (SOD) activity, heme oxygenase-1 (HO-1), NADP(H) quinone oxidoreductase 1 (NQO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) expressions. In contrast, high levels of MDA and kelch-like ECH-associated protein 1 (Keap 1) in LPS-treated mice were down-regulated by APT, which might be associated with the inactivation of NF-κB. In vitro, APT exhibited anti-inflammatory and anti-oxidant effects with little cytotoxicity in LPS-stimulated cells. Together, the data above indicated that APT could ameliorate acute otitis media through inhibiting inflammation and oxidative stress.


The effect of surgical operation on growth hormone levels in plasma.
This study was designed to clarify the details of any changes in serum growth hormone levels occurring in surgical patients. Intravenous glucose tolerance tests were performed upon three groups of six patients each, Group I, minor surgery (inguinal herniorrhaphy), Group II, moderate surgery (vagotomy and pyloroplasty), and Group III, major surgery (aortofemoral bypass). Plasma glucose and serum growth hormone levels were measured. Depression of glucose utilization occurred together with elevations of fasting growth hormone levels and increased growth hormone responses to intravenous glucose. It is suggested that the increased serum growth hormone levels are a response to the glucose intolerance caused by operation, modifying the pituitary growth hormone release.


[Determination of total quantity of rare earths, Ca, Mg, Mn and Fe in rare-earths-magnesium by ICP-AES with offset profile add lines].
This article introduced a method for the determination of total quantity of rare earths, Ca, Mg, Mn and Fe in rare-earths-magnesium with ICP-AES. The total quantity of rare-earths was calculated by the quantum of cerium, the measurement channel of cerium was fixed by the method of Offset Profile Add Lines, by changing the entrance slit angle, based on the fixed channels of the ICP-AES. The sample was melted with HNO3, HF, HClO4 and HCl, the difficulty of melting sample was properly settled. The method of internal standard was used in the determination, cobalt elected for the internal standard, and the same concentration cobalt liquor was added in the sample liquor. This article made the measurement parameters test, for example the quantum of pump, the height of observation, etc, and examined the liner range, accuracy, background equal concentration, detection limits and precision. The results showed that the method was simpler than chemical analytic method in operating, and could simultaneously determined many kinds of elements. It was compared with chemical method, the results were satisfactory.


Characterization of novel cell lines derived from a MYC-driven murine model of lethal metastatic adenocarcinoma of the prostate.
Loss or mutation of PTEN alleles at 10q23 in combination with 8q24 amplification (encompassing MYC) are common findings in aggressive, human prostate cancer. Our group recently developed a transgenic murine model of prostate cancer involving prostate-specific Pten deletion and forced expression of MYC under the control of the Hoxb13 promoter. MYC overexpression cooperated with Pten loss to recapitulate lethal, human prostate cancer. We now report on the generation of two mouse prostate cancer cell lines, BMPC1 and BMPC2, derived from a lymph node, and liver metastasis, respectively. Both cell lines demonstrate a phenotype consistent with adenocarcinoma and grew under standard tissue culture conditions. Androgen receptor (AR) protein expression is minimal (BMPC1) or absent (BMPC2) consistent with AR loss observed in the BMPC mouse model of invasive adenocarcinoma. Growth in media containing charcoal-stripped serum resulted in an increase in AR mRNA in BMPC1 cells with no effect on protein expression, unless androgens were added, in which case AR protein was stabilized, and showed nuclear localization. AR expression in BMPC2 cells was not effected by growth media or treatment with androgens. Treatment with an anti-androgen/castration or androgen supplemented media did not affect in vitro or in vivo growth of either cell line, irrespective of nuclear AR detection. These cell lines are a novel model of androgen-insensitive prostatic adenocarcinoma driven by MYC over-expression and Pten loss.


Associations between falls and general health, nutrition, dental health and medication use in Swedish home-dwelling people aged 75 years and over.
The vast majority of elderly people in Sweden live in private homes in their communities for as long as possible. Poor health and a high risk of falls are very common among this group. This cross-sectional study investigates the association between falls and general health, appetite, dental health, and the use of multiple medications among home-dwelling men and women aged ≥ 75 years. Data were collected between October 2008 and March 2009 using a postal questionnaire. A total of 1243 people participated in the questionnaire survey (74% response rate), of which 1193 were included in the analysis. The majority of participants were women (n = 738, 62%). Falls in the previous 12-month period were reported by 434 (36%) participants. Most fallers (n = 276, 64%) were women. The majority of the fallers lived in a flat (n = 250, 58%). Poor health (aOR: 1.61; CI: 1.34-1.95), poor dental health (aOR: 1.22; CI: 1.07-1.39) and the use of four or more types of medication daily (aOR: 1.13; CI: 1.03-1.25) were significantly associated with falls in all participants. Poor dental health was found irrespectively of living in a flat (aOR: 1.23; CI: 1.04-1.46) or living in a house (aOR: 1.28; CI: 1.02-1.61), and both were significantly associated with falls. The use of more than four different types of medication daily (aOR: 1.25; CI: 1.11-1.41) was associated with falls for those living in a flat. The results highlight that falls are associated with poor general health, poor dental health and the use of four or more types of medication daily. Health professionals should provide health promotion education and investigate dental health and risk factors for oral disease. Likewise, medical and clinical practices of physicians and community care nurses should include assessing the risk of falling, and treatment that predisposes falls.


Effects of Partial Beef Fat Replacement with Gelled Emulsion on Functional and Quality Properties of Model System Meat Emulsions.
The objective of this study was to investigate the effects of partial beef fat replacement (0, 30, 50, 100%) with gelled emulsion (GE) prepared with olive oil on functional and quality properties of model system meat emulsion (MSME). GE consisted of inulin and gelatin as gelling agent and characteristics of gelled and model system meat emulsions were investigated. GE showed good initial stability against centrifugation forces and thermal stability at different temperatures. GE addition decreased the pH with respect to increase in GE concentration. Addition of GE increased lightness and yellowness but reduced redness compared to control samples. The results of the study showed that partial replacement of beef fat with GE could be used for improving cooking yield without negative effects on water holding capacity and emulsion stability compared to C samples when replacement level is up to 50%. The presence of GE significantly affected textural behaviors of samples (p<0.05). In conclusion, our study showed that GE have promising impacts on developing healthier meat product formulations besides improving technological characteristics.


A Complex Relationship: Intimate Partner Violence, Identification With the Aggressor, and Guilt.
This study explored the relation between guilt and identification with the aggressor (IWA) and the moderating role of IWA in the relation between intimate partner violence (IPV) and guilt. An online survey was conducted among a convenience sample of 700 women. IPV survivors demonstrated elevated guilt, and IWA was related to guilt. Furthermore, IWA moderated the relation between IPV and guilt: Among participants with low IWA levels, IPV was unrelated to guilt, but among participants with high IWA levels, IPV was related to guilt. These findings suggest that IWA may be a key element in explaining guilt among IPV survivors.


[Implications of prostaglandins in neoplastic processes of human glandular epithelia, particularly the breast and prostate].
Prostaglandins (PGs) are a family of lipid compounds synthesized from polyunsaturated fatty acids derived from phospholipids, and divided into three main classes: primary PGs (including prostacyclin), thromboxanes, and leukotrienes. Though each member possesses marked activity on certain human biological functions, their precise role in physiological processes is uncertain, as they are present in very low quantities under normal or resting condition but show a marked increase in levels during benign or malignant pathological processes. This report mainly concerns neoplastic and preneoplastic phenomena, when PGs production is presented as being the consequence of altered cell function. This results from loss of the physiological state of tissue dependence of the cells, which acquire functional autonomy and become endowed with properties which appear to be important in cancer dissemination processes.


Adsorption onto Mesoporous Silica Using Supercritical Fluid Technology Improves Dissolution Rate of Carbamazepine-a Poorly Soluble Compound.
The purpose of this research was to design and characterize an immediate-release formulation of carbamazepine (CBZ), a poorly soluble anti-epileptic drug, using a porous silica carrier. Carbon dioxide in its supercritical state (2000 psi, 30-35°C) was used as an anti-solvent to precipitate CBZ onto two particle size variants of silica. Adsorption isotherms were used as a pre-formulation strategy to select optimum ratios of silica and CBZ. The obtained drug-silica formulations were characterized by dissolution studies, differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). This formulation strategy resulted in a 2.4-fold improvement in dissolution rate when compared to pure drug after 30 min of dissolution testing. PXRD and DSC confirmed the amorphous nature of CBZ in the formulations as well as the differences in polymorphic forms of commercial and supercritical fluid-processed CBZ. Additionally, solid-state NMR spectroscopy showed that the spin-lattice relaxation time for bulk drug (without silica) was ∼7.5 times greater than that for silica-confined CBZ, implying that when CBZ was adsorbed onto mesoporous silica, it is structurally disordered and had higher structural mobility, a characteristic of amorphous solids. The mesoporous silica matrix prevented CBZ crystal growth by imposing spatial constraint on CBZ nuclei and hence resulted in faster dissolution compared to bulk solid drug. Adsorption onto mesoporous silica using supercritical fluid technology may be used as a novel formulation strategy for amorphization of poorly soluble compounds, in turn improving their dissolution rate.


Adverse reactions to antiarrhythmic drugs during therapy for ventricular arrhythmias.
We analyzed the incidence of adverse reactions to antiarrhythmic drugs in 123 consecutive patients with a history of sustained ventricular tachycardia or ventricular fibrillation. Blood levels were measured serially and were maintained within the usual therapeutic range. Minor reactions were defined as those that required dosage reduction and major reactions as those that required drug discontinuation or permanent pacing for bradycardia. A total of 237 individual, oral drug trials were evaluated in the 123 patients. Adverse reactions were noted in 79 trials (33%). Fifty-nine (48%) of the 123 patients had one or more adverse reaction. Major reactions were noted in 36 patients (29%). Adverse effects occurred during 49% of trials with mexiletine hydrochloride, 44% of trials with amiodarone, 24% of trials with procainamide hydrochloride, and 18% of trials with quinidine sulfate or gluconate. In conclusion, clinically significant adverse reactions are common during drug therapy for ventricular arrhythmias. These observations indicate that with the drugs used in this study, an acceptable risk-benefit ratio will be possible only in patients at a significant risk for a symptomatic arrhythmia. Antiarrhythmic drug therapy in patients at low risk for serious arrhythmia should be discouraged.


Anxiety in early pregnancy: prevalence and contributing factors.
Antenatal anxiety symptoms are not only a health problem for the expectant mother. Research has found that maternal anxiety may also have an impact on the developing baby. Therefore, it is important to estimate the prevalence of maternal anxiety and associated factors. The current study aims to estimate the prevalence of anxiety symptoms during the first trimester of pregnancy and to identify associated risk factors. Secondly, to investigate other factors associated with anxiety during early pregnancy including fear of childbirth and a preference for cesarean section. In a population-based community sample of 1,175 pregnant women, 916 women (78%) were investigated in the first trimester (gestation week 8-12). The Hospital Anxiety Depression Scale (HADS-A) was used to measure anxiety symptoms. The prevalence of anxiety symptoms (HADS-A scores≥8 during pregnancy) was 15.6% in early pregnancy. Women under 25 years of age were at an increased risk of anxiety symptoms during early pregnancy (OR 2.6, CI 1.7-4.0). Women who reported a language other than Swedish as their native language (OR 4.2, CI 2.7-7.0), reported high school as their highest level of education (OR 1.6, CI 1.1-2.3), were unemployed (OR 3.5, CI 2.1-5.8), used nicotine before pregnancy (OR 1.7, CI 1.1-2.5), and had a self-reported psychiatric history of either depression (OR 3.8, CI 2.6-5.6) or anxiety (OR 5.2, CI 3.5-7.9) before their current pregnancy were all at an increased risk of anxiety symptoms during early pregnancy. Anxiety symptoms during pregnancy increased the rate of fear of birth (OR 3.0, CI 1.9-4.7) and a preference for cesarean section (OR 1.7, CI 1.0-2.8). Caregivers should pay careful attention to history of mental illness to be able to identify women with symptoms of anxiety during early pregnancy. When presenting with symptoms of anxiety, the women might need counseling and or treatment in order to decrease her anxiety.


[Practical use of low molecular weight heparins in angiology].
The recent development of low molecular weight heparins (LMWH), obtained by the depolymerization of standard non-fractioned heparin (NFH), considerably simplifies the course of anticoagulant treatments. They now allow effectively and safely dealing with the risks of thrombosis, both in hospital and at the patient's home. Their effectiveness for both the prevention and the treatment of thromboembolic accidents has been proved by many clinical trials. In comparison to standard heparin, the LMWHs still have a high anti-Xa activity, but their anti-IIa action is much reduced, thus preserving their antithrombotic power while reducing the hemorrhagic risks. Owing to their better bioavailability and longer half-life, they allow using in priority the subcutaneous route, reducing the frequency of the injections and simplifying surveillance, without impairing the effectiveness of the treatment. The prevention of thrombosis with LMWHs requires one daily subcutaneous dose. The control of the anti-Xa activity is not necessary for the doses used. Prior to initiating a curative treatment, it is essential to confirm the existence of thrombosis. When the diagnosis is definitive, the three LMWHs currently known are used after reconversion, at a dosage of 100 IU/kg/12 hrs. The anti-Xa activity, in samples taken 3 to 4 hours after the injection, must be maintained between 0.5 and 1 IU anti-Xa/ml. It is prudent to control the platelet level at D5 and D10, although thrombocytopenia is exceptional. The changeover treatment with antivitamins K (AVK), which is essential to prevent the recurrence of venous thrombosis, is initiated very early (2nd or 3rd day).(ABSTRACT TRUNCATED AT 250 WORDS)


A live term intra-abdominal pregnancy in a Field Hospital: a case report.
Abdominal pregnancy is a rare form of ectopic pregnancy with high morbidity and mortality for both the mother and the fetus. Diagnosis can be challenging, especially in a resource-limited setting. We report a case of abdominal pregnancy that presented to Médecins Sans Frontières field hospital in Agok, South Sudan, with abdominal pain. Examination revealed a term pregnancy and a live fetus in transverse lie. The diagnosis of abdominal pregnancy was made intraoperatively, with successful management and delivery of a healthy baby.


Interferon-gamma receptor deficiency: relationship between genotype, environment, and phenotype (Review).
Interferon-gamma receptor ligand binding chain (IFNgammaR1) deficiency is an autosomal recessive inherited immune disorder. Mutations in the IFNgR1 gene are associated with severe infections due to mycobacteria. However, several aspects of the phenotype of IFNgammaR1-deficient children have recently been found to vary from case to case. This review thus discusses the respective roles of the genotype and of the environment in determining phenotypic variations among affected children.


Frank-ter Haar syndrome protein Tks4 regulates epidermal growth factor-dependent cell migration.
Mutations in the SH3PXD2B gene coding for the Tks4 protein are responsible for the autosomal recessive Frank-ter Haar syndrome. Tks4, a substrate of Src tyrosine kinase, is implicated in the regulation of podosome formation. Here, we report a novel role for Tks4 in the EGF signaling pathway. In EGF-treated cells, Tks4 is tyrosine-phosphorylated and associated with the activated EGF receptor. This association is not direct but requires the presence of Src tyrosine kinase. In addition, treatment of cells with LY294002, an inhibitor of PI 3-kinase, or mutations of the PX domain reduces tyrosine phosphorylation and membrane translocation of Tks4. Furthermore, a PX domain mutant (R43W) Tks4 carrying a reported point mutation in a Frank-ter Haar syndrome patient showed aberrant intracellular expression and reduced phosphoinositide binding. Finally, silencing of Tks4 was shown to markedly inhibit HeLa cell migration in a Boyden chamber assay in response to EGF or serum. Our results therefore reveal a new function for Tks4 in the regulation of growth factor-dependent cell migration.


Effect of baseline oestradiol serum concentration on the efficacy of anastrozole for preventing breast cancer in postmenopausal women at high risk: a case-control study of the IBIS-II prevention trial.
An increased risk of breast cancer is associated with high serum concentrations of oestradiol and testosterone in postmenopausal women, but little is known about how these hormones affect response to endocrine therapy for breast cancer prevention or treatment. We aimed to assess the effects of serum oestradiol and testosterone concentrations on the efficacy of the aromatase inhibitor anastrozole for the prevention of breast cancer in postmenopausal women at high risk. In this case-control study we used data from the IBIS-II prevention trial, a randomised, controlled, double-blind trial in postmenopausal women aged 40-70 years at high risk of breast cancer, conducted in 153 breast cancer treatment centres across 18 countries. In the trial, women were randomly assigned (1:1) to receive anastrozole (1 mg/day, orally) or placebo daily for 5 years. In this pre-planned case-control study, the primary analysis was the effect of the baseline oestradiol to sex hormone binding globulin (SHBG) ratio (oestradiol-SHBG ratio) on the development of all breast cancers, including ductal carcinoma in situ (the primary endpoint in the trial). Cases were participants in whom breast cancer was reported after trial entry and until the cutoff on Oct 22, 2019, and who had valid blood samples and no use of hormone replacement therapy within 3 months of trial entry or during the trial. For each case, two controls without breast cancer were selected at random, matched on treatment group, age (within 2 years), and follow-up time (at least that of the matching case). For each treatment group, we applied a multinominal logistic regression likelihood-ratio trend test to assess what change in the proportion of cases was associated with a one-quartile change in hormone ratio. Controls were used only to determine quartile cutoffs. Profile likelihood 95% CIs were used to indicate the precision of estimates. A secondary analysis also investigated the effect of the baseline testosterone-SHBG ratio on breast cancer development. We also assessed relative benefit of anastrozole versus placebo (calculated as 1 - the ratio of breast cancer cases in the anastrozole group to cases in the placebo group). The trial was registered with ISRCTN (number ISRCTN31488319) and completed recruitment on Jan 31, 2012, but long-term follow-up is ongoing. 3864 women were recruited into the trial between Feb 2, 2003, and Jan 31, 2012, and randomly assigned to receive anastrozole (n=1920) or placebo (n=1944). Median follow-up time was 131 months (IQR 106-156), during which 85 (4·4%) cases of breast cancer in the anastrozole group and 165 (8·5%) in the placebo group were identified. No data on gender, race, or ethnicity were collected. After exclusions, the case-control study included 212 participants from the anastrozole group (72 cases, 140 controls) and 416 from the placebo group (142 cases, 274 controls). A trend of increasing breast cancer risk with increasing oestradiol-SHBG ratio was found in the placebo group (trend per quartile 1·25 [95% CI 1·08 to 1·45], p=0·0033), but not in the anastrozole group (1·06 [0·86 to 1·30], p=0·60). A weaker effect was seen for the testosterone-SHBG ratio in the placebo group (trend 1·21 [1·05 to 1·41], p=0·011), but again not in the anastrozole group (trend 1·18 [0·96 to 1·46], p=0·11). A relative benefit of anastrozole was seen in quartile 2 (0·55 [95% CI 0·13 to 0·78]), quartile 3 (0·54 [0·22 to 0·74], and quartile 4 (0·56 [0·23 to 0·76]) of oestradiol-SHBG ratio, but not in quartile 1 (0·18 [-0·60 to 0·59]). These results suggest that serum hormones should be measured more routinely and integrated into risk management decisions. Measuring serum hormone concentrations is inexpensive and might help clinicians differentiate which women will benefit most from an aromatase inhibitor. Cancer Research UK, National Health and Medical Research Council (Australia), Breast Cancer Research Foundation, and DaCosta Fund.


Supplementing behavioral marital therapy with cognitive restructuring and emotional expressiveness training: an outcome investigation.
The current study investigated whether the effectiveness of behavioral marital therapy (BMT) would be increased by the addition of cognitive restructuring (CR) and/or emotional expressiveness training (EET) for maritally distressed couples. Sixty such couples were randomly assigned to 1 of 3 therapists and 1 of 5 treatment conditions (BMT Alone, CR + BMT, BMT + EET, CR + BMT + EET, or waiting list) for 12 weeks of conjoint marital therapy. Within each treatment condition, couples typically improved on the variables focused on in treatment. However, comparisons among active treatment conditions showed few significant differences among treatments; the treatments were equally effective in increasing marital adjustment. Thus, the addition of CR and EET did not appear to increase the overall effectiveness of treatment. Possible reasons for the current findings are provided, and suggestions for future marital outcome investigations are outlined.


A Review of OCT Angiography in Glaucoma.
There is growing evidence that vascular dysfunction plays a role in the pathogenesis of glaucoma. The details of this relationship have remained elusive partially due to limitations in our ability to assess blood flow in the optic nerve. Optical coherence tomography angiography (OCTA) has emerged as a promising new technology well positioned to become the first clinically suitable test of optic nerve perfusion. OCTA uses the motion of red blood cells as an intrinsic contrast agent to create reproducible images of microvascular networks rapidly and non-invasively. A significant body of research regarding the use of OCTA in glaucoma has emerged in recent years. This review aims to provide an overview of the basic principles underlying OCTA technology, summarize the current literature regarding the application of OCTA in the management of glaucoma, and address the role of OCTA in explicating the vascular pathogenesis of glaucoma.


[Prevention of duodenal ulcer recurrence. A new prospect].
Prevention of recurrence is now the main therapeutic problem in the management of duodenal ulcer disease. It has been shown that in the absence of maintenance treatment the mean recurrence rate within 6 to 12 months from healing obtained with drugs other than H2-receptor antagonists (H2A) is lower than when healing is obtained with H2A. Possible reasons for this discrepancy are examined. When the recurrence rates observed with each of the non-H2A drugs were compared individually with those observed with H2A, the only important and constant difference was in favour of colloidal bismuth subcitrate (CBS). This beneficial effect of CBS is due to its bactericidal action on Helicobacter pylori. Unlike healing, prevention of recurrent ulcer is primarily, if not exclusively, related to eradication of this organism. Although the ideal treatment providing both healing of duodenal ulcers and eradication of Helicobacter pylori has not yet been determined (CBS administered alone eradicates this organism in only 10 to 25 percent of cases), it will soon be possible to modify dramatically the natural course of duodenal ulcer disease and even to obtain its cure.


Effects of Radiotherapy and Chemotherapy on Platelet in Patients with Lung Cancer.
An animal study has shown that platelets form are formed in the lungs. Therefore, we wanted to study the relationship between lung radiation dose and platelet count in lung cancer patients receiving radiation therapy. This retrospective study included 93 patients with lung cancer who received radical thoracic radiation therapy. The correlation between pulmonary dose-volume histogram (DVH) parameters and thrombocytopenia during radiotherapy (RT) was evaluated by chi-square test, logistic regression analysis, Spearman and Pearson correlation analysis, etc. Results: Thrombocytopenia occurred in 17 of 93 patients (18.3%). Chi-square test and logistic regression analysis showed that chemotherapy (p = 0.038), MLD (mean lung dose, p = 0.001), V5 (p = 0.008), V10 (p = 0.004), AND V20 (p = 0.003) were important independent predictors of thrombocytopenia. Using the chi-square test, increased MLD (p = 0.002), V5 (p = 0.021), V10 (p = 0.008), and V20 (p = 0.006) were associated with increased risk of thrombocytopenia. Receiver operating characteristic (ROC) curve was used to analyze the thresholds of MLD, V5, V10, and V20, which showed high sensitivity and specificity for distinguishing between non-thrombocytopenia and thrombocytopenia. Higher doses of radiation to the lung are associated with an increased risk of thrombocytopenia. Moreover, optimization of treatment plans via the control of DVH parameters may reduce treatment interruptions and improve outcomes in lung cancer patients treated with RT.


Advocating for a Loved One in the Setting of Uncertainty: A Mixed-Methods Study Among Caregivers of Sepsis Survivors at the Point of a Sepsis Readmission.
The trajectory of recovery after sepsis varies. Survivors may have considerable ongoing limitations, requiring a caregiver for a prolonged period. To learn about experiences, quality of life, coping, resilience, and social support of caregiver caring for survivors of sepsis. We conducted a convergent mixed-methods study, recruiting informal caregivers of patients who had survived sepsis in the past year and were readmitted to the intensive care unit with sepsis. Individual face-to-face, semistructured interviews and validated surveys on quality of life, coping, caregiver burden, resilience, and social support were administered to caregivers. Interview transcripts were analyzed using content analysis. Surveys were scored and summarized using descriptive statistics. Caregivers were primarily middle-aged, White, and female. Half were spouses of their care recipient. Caregivers reported some deficits in mobility, pain, and anxiety/depression. Coping styles varied, with engaged coping being more prevalent. Most caregivers reported mild to moderate burden, all reported either normal or high resilience levels, and types of social support were similar. However, interviews and survey findings were not always consistent. Major themes that emerged from the analysis included (1) advocating for and protecting their loved one, (2) coping with caregiving, (3) uncertain future, (4) rewards of caregiving, and (5) need to optimize communication with family. Caregivers of sepsis survivors are protective of their care recipient and use a variety of strategies to advocate for their loved one and to cope with the uncertainty involved in a new intensive care unit admission. More advocacy and support are needed for this population.


Small bowel obstruction- a surprise.
Trans - omental hernia is very rare, accounting to 1-4% of all internal hernias which is an unusual cause of small bowel obstruction. Here we present a case report of a small bowel obstruction in a female due to trans - omental hernia presenting with central abdominal pain, distension and bilious vomiting. She had no previous history of trauma, surgery. Plain X-ray abdomen erect showed multiple air fluid levels with dilated small bowel loops. Emergency laparotomy revealed a segment of congested small bowel loop (ileum) through a defect in greater omentum. On table the herniated bowel loop was reduced and the defect in greater omentum was closed primarily. There was no necessity for bowel resection as it regained normal colour after reduction. Postoperative period was uneventful with complete resolution of symptoms. This case is presented for its rarity and its importance in clinical differential diagnosis of acute abdomen due to small bowel obstruction.


Chinese hamster ovary cells replicate adenovirus deoxyribonucleic acid.
Chinese hamster ovary (CHO) cells infected with adenovirus type 2 (Ad2) produced amounts of viral deoxyribonucleic acid (DNA) equal to that synthesized in permissively infected HeLa cells. However, there was 6,000-fold less virion produced in CHO cells. Since the structural viral polypeptides were not detected by pulse-labeling CHO cells at various times postinfection, the block in virion formation is located between the synthesis of viral DNA and late proteins. Extracts of CHO cells could also function in a recently reported in vitro Ad2 DNA synthesis system which is dependent upon the addition of exogenous Ad2 DNA covalently linked to a 5'-terminal protein (Ikeda et al., Proc. Natl. Acad. Sci. U.S.A. 77:5827-5831, 1980). Extracts of infected CHO cytoplasm were able to complement uninfected CHO nuclear extracts to synthesize viral DNA on Ad2 templates. This in vitro replication system has the potential to probe host DNA synthesis requirements as well as viral factors.


Dehydroalkylative Activation of CNN- and PNN-Pincer Ruthenium Catalysts for Ester Hydrogenation.
Ruthenium-pincer complexes bearing CNN- and PNN-pincer ligands with diethyl- or diisopropylamino side groups, which have previously been reported to be active precatalysts for ester hydrogenation, undergo dehydroalkylation on heating in the presence of tricyclohexylphosphine to release ethane or propane, giving five-coordinate ruthenium(0) complexes containing a nascent imine functional group. Ethane or propane is also released under the conditions of catalytic ester hydrogenation, and time-course studies show that this release is concomitant with the onset of catalysis. A new PNN-pincer ruthenium(0)-imine complex is a highly active catalyst for ester hydrogenation at room temperature, giving up to 15 500 turnovers with no added base. This complex was shown to react reversibly at room temperature with two equivalents of hydrogen to give a ruthenium(II)-dihydride complex, where the imine functionality has been hydrogenated to give a protic amine side group. These observations have potentially broad implications for the identities of catalytic intermediates in ester hydrogenation and related transformations.


Correlation of hypointensities in susceptibility-weighted images to tissue histology in dementia patients with cerebral amyloid angiopathy: a postmortem MRI study.
Neuroimaging with iron-sensitive MR sequences [gradient echo T2* and susceptibility-weighted imaging (SWI)] identifies small signal voids that are suspected brain microbleeds. Though the clinical significance of these lesions remains uncertain, their distribution and prevalence correlates with cerebral amyloid angiopathy (CAA), hypertension, smoking, and cognitive deficits. Investigation of the pathologies that produce signal voids is necessary to properly interpret these imaging findings. We conducted a systematic correlation of SWI-identified hypointensities to tissue pathology in postmortem brains with Alzheimer's disease (AD) and varying degrees of CAA. Autopsied brains from eight AD patients, six of which showed advanced CAA, were imaged at 3T; foci corresponding to hypointensities were identified and studied histologically. A variety of lesions was detected; the most common lesions were acute microhemorrhage, hemosiderin residua of old hemorrhages, and small lacunes ringed by hemosiderin. In lesions where the bleeding vessel could be identified, β-amyloid immunohistochemistry confirmed the presence of β-amyloid in the vessel wall. Significant cellular apoptosis was noted in the perifocal region of recent bleeds along with heme oxygenase 1 activity and late complement activation. Acutely extravasated blood and hemosiderin were noted to migrate through enlarged Virchow–Robin spaces propagating an inflammatory reaction along the local microvasculature; a mechanism that may contribute to the formation of lacunar infarcts. Correlation of imaging findings to tissue pathology in our cases indicates that a variety of CAA-related pathologies produce MR-identified signal voids and further supports the use of SWI as a biomarker for this disease.


Project VOGUE: A partnership for increasing HIV knowledge and HIV vaccine trial awareness among House Ball leaders in Western New York.
Men who sleep with men (MSM) and transgender individuals of color, the largest demographic in the House Ball community (HBC) are amongst the group at highest risk for HIV infection in the United States. The HBC have limited access to culturally appropriate HIV education. This study aimed to develop a partnership with HBC leaders to uncover strategies for increasing HIV prevention knowledge, including participation in HIV vaccine trials. To this end a research institution-community-HBC partnership was established. In-depth qualitative and quantitative data were collected from the 14 HBC leaders in western New York, revealing that knowledge of HIV and related vaccine trials was limited. Barriers to increasing HIV knowledge included fear of peer judgment, having inaccurate information about HIV, and lack of education. Among the HBC, community partnerships will further aid in the development of future HIV prevention programs and increase individuals' willingness to participate in future HIV vaccine trials.


The comparative safety of opioids for nonmalignant pain in older adults.
Severe nonmalignant pain affects a large proportion of adults. Optimal treatment is not clear, and opioids are an important option for analgesia. However, there is relatively little information about the comparative safety of opioids. Therefore, we sought to compare the safety of opioids commonly used for nonmalignant pain. We devised a propensity-matched cohort analysis that used health care utilization data collected from January 1, 1996, through December 31, 2005. Study participants were Medicare beneficiaries from 2 US states who were new initiators of opioid therapy for nonmalignant pain, including codeine phosphate, hydrocodone bitartrate, oxycodone hydrochloride, propoxyphene hydrochloride, and tramadol hydrochloride; none had a cancer diagnosis, and none were using hospice or nursing home care. Our main outcome measures were incidence rates and rate ratios (RRs) with 95% confidence intervals (CIs) for cardiovascular events, fractures, gastrointestinal events, and several composite end points. We matched 6275 subjects in each of the 5 opioid groups. The groups were well matched on baseline characteristics. The risk of cardiovascular events was similar across opioid groups 30 days after the start of opioid therapy, but it was elevated for codeine (RR, 1.62; 95% CI, 1.27-2.06) after 180 days. Compared with hydrocodone, after 30 days of opioid exposure the risk of fracture was significantly reduced for tramadol (RR, 0.21; 95% CI, 0.16-0.28) and propoxyphene (0.54; 0.44-0.66) users. The risk of gastrointestinal safety events did not differ across opioid groups. All-cause mortality was elevated after 30 days for oxycodone (RR, 2.43; 95% CI, 1.47-4.00) and codeine (2.05; 1.22-3.45) users compared with hydrocodone users. The rates of safety events among older adults using opioids for nonmalignant pain vary significantly by agent. Causal inference requires experimental designs, but these results should prompt caution and further study.


Viscoelasticity of thin biomolecular films: a case study on nucleoporin phenylalanine-glycine repeats grafted to a histidine-tag capturing QCM-D sensor.
Immobilization of proteins onto surfaces is useful for the controlled generation of biomolecular assemblies that can be readily characterized with in situ label-free surface-sensitive techniques. Here we analyze the performance of a quartz crystal microbalance with dissipation monitoring (QCM-D) sensor surface that enables the selective and oriented immobilization of histidine-tagged molecules for morphological and interaction studies. More specifically, we characterize monolayers of natively unfolded nucleoporin domains that are rich in phenylalanine-glycine repeats (FGRDs). An FGRD meshwork is thought to be responsible for the selectivity of macromolecular transport across the nuclear pore complex between the cytosol and the nucleus of living cells. We demonstrate that nucleoporin FGRD films can be formed on His-tag Capturing Sensors with properties comparable to a previously reported immobilization platform based on supported lipid bilayers (SLB). Approaches to extract the film thickness and viscoelastic properties in a time-resolved manner from the QCM-D response are described, with particular emphasis on the practical implementation of viscoelastic modeling and a detailed analysis of the quality and reliability of the fit. By comparing the results with theoretical predictions for the viscoelastic properties of polymer solutions and gels, and experimental data from an atomic force microscopy indentation assay, we demonstrate that detailed analysis can provide novel insight into the morphology and dynamics of FG repeat domain films. The immobilization approach is simple and versatile, and can be easily extended to other His-tagged biomolecules. The data analysis procedure should be useful for the characterization of other ultrathin biomolecular and polymer films.


Adverse effects of cannabis.
Cannabis, Cannabis sativa L., is used to produce a resin that contains high levels of cannabinoids, particularly delta9-tetrahydrocannabinol (THC), which are psychoactive substances. Although cannabis use is illegal in France and in many other countries, it is widely used for its relaxing or euphoric effects, especially by adolescents and young adults. What are the adverse effects of cannabis on health? During consumption? And in the long term? Does cannabis predispose users to the development of psychotic disorders? To answer these questions, we reviewed the available evidence using the standard Prescrire methodology. The long-term adverse effects of cannabis are difficult to evaluate. Since and associated substances, with or without the user's knowledge. Tobacco and alcohol consumption, and particular lifestyles and behaviours are often associated with cannabis use. Some traits predispose individuals to the use of psychoactive substances in general. The effects of cannabis are dosedependent.The most frequently report-ed adverse effects are mental slowness, impaired reaction times, and sometimes accentuation of anxiety. Serious psychological disorders have been reported with high levels of intoxication. The relationship between poor school performance and early, regular, and frequent cannabis use seems to be a vicious circle, in which each sustains the other. Many studies have focused on the long-term effects of cannabis on memory, but their results have been inconclusive. There do not * About fifteen longitudinal cohort studies that examined the influence of cannabis on depressive thoughts or suicidal ideation have yielded conflicting results and are inconclusive. Several longitudinal cohort studies have shown a statistical association between psychotic illness and self-reported cannabis use. However, the results are difficult to interpret due to methodological problems, particularly the unknown reliability of self-reported data. It has not been possible to establish a causal relationship in either direction, because of these methodological limitations. In Australia, the marked increase in cannabis use has not been accompanied by an increased incidence of schizophrenia. On the basis of the available data, we cannot reach firm conclusions on whether or not cannabis use causes psychosis. It seems prudent to inform apparently vulnerable individuals that cannabis may cause acute psychotic decompensation, especially at high doses. Users can feel dependent on cannabis, but this dependence is usually psychological. Withdrawal symptoms tend to occur within 48 hours following cessation of regular cannabis use, and include increased irritability, anxiety, nervousness, restlessness, sleep difficulties and aggression. Symptoms subside within 2 to 12 weeks. Driving under the influence of cannabis doubles the risk of causing a fatal road accident. Alcohol consumption plays an even greater role. A few studies and a number of isolated reports suggest that cannabis has a role in the occurrence of cardiovascular adverse effects, especially in patients with coronary heart disease. Numerous case-control studies have investigated the role of cannabis in the incidence of some types of cancer. Its role has not been ruled out, but it is not possible to determine whether the risk is distinct from that of the tobacco with which it is often smoked. Studies that have examined the influence of cannabis use on the clinical course of hepatitis C are inconclusive. Alcohol remains the main toxic agent that hepatitis C patients should avoid. In practice, the adverse effects of low-level, recreational cannabis use are generally minor, although they can apparently be serious in vulnerable individuals. The adverse effects of cannabis appear overall to be less serious than those of alcohol, in terms of neuropsychological and somatic effects, accidents and violence.


[Treatment of erectile dysfunction - from pill to implant].
The article gives an overview of erectile mechanisms and erectile dysfunction (ED). Current treatment of ED is presented. Most of the patients with ED should be treated by their primary care physician. Urologists should be involved only when treatment has failed, and when erectile implants might be an option. In Skåne the waiting list for these patients has been eliminated by using the operating capacity of a smaller hospital.


Magnetic resonance imaging connectivity for the prediction of seizure outcome in temporal lobe epilepsy.
Currently, approximately 60-70% of patients with unilateral temporal lobe epilepsy (TLE) remain seizure-free 3 years after surgery. The goal of this work was to develop a presurgical connectivity-based biomarker to identify those patients who will have an unfavorable seizure outcome 1-year postsurgery. Resting-state functional and diffusion-weighted 3T magnetic resonance imaging (MRI) was acquired from 22 unilateral (15 right, 7 left) patients with TLE and 35 healthy controls. A seizure propagation network was identified including ipsilateral (to seizure focus) and contralateral hippocampus, thalamus, and insula, with bilateral midcingulate and precuneus. Between each pair of regions, functional connectivity based on correlations of low frequency functional MRI signals, and structural connectivity based on streamline density of diffusion MRI data were computed and transformed to metrics related to healthy controls of the same age. A consistent connectivity pattern representing the network expected in patients with seizure-free outcome was identified using eight patients who were seizure-free at 1-year postsurgery. The hypothesis that increased similarity to the model would be associated with better seizure outcome was tested in 14 other patients (Engel class IA, seizure-free: n = 5; Engel class IB-II, favorable: n = 4; Engel class III-IV, unfavorable: n = 5) using two similarity metrics: Pearson correlation and Euclidean distance. The seizure-free connectivity model successfully separated all the patients with unfavorable outcome from the seizure-free and favorable outcome patients (p = 0.0005, two-tailed Fisher's exact test) through the combination of the two similarity metrics with 100% accuracy. No other clinical and demographic predictors were successful in this regard. This work introduces a methodologic framework to assess individual patients, and demonstrates the ability to use network connectivity as a potential clinical tool for epilepsy surgery outcome prediction after more comprehensive validation.


Chronic Allergen Challenge Induces Corticosteroid Insensitivity With Persistent Airway Remodeling and Type 2 Inflammation.
Type 2-high severe asthma is described as a distinct endotype with Th2 inflammation, high eosinophil lung infiltration, impaired lung function, and reduced corticosteroid sensitivity. While the inflammatory milieu is similar to mild asthma, patients with type 2-high severe asthma likely have underlying mechanisms that sustain asthma pathophysiology despite corticosteroid treatments. Acute and chronic allergen models induce robust type 2 inflammatory responses, however differences in corticosteroid sensitivity remains poorly understood. In the present study, we sensitized and challenged mice with ovalbumin (OVA; acute model) or mixed allergens (MA; chronic model). Corticosteroid sensitivity was assessed by administering vehicle, 1, or 3 mg/kg fluticasone propionate (FP) and examining key asthmatic features such as airway inflammation, remodeling, hyperresponsiveness, and antioxidant capacity. Both acute and chronic allergen exposure exhibited enhanced AHR, immune cell infiltration, airway inflammation, and remodeling, but corticosteroids were unable to fully alleviate inflammation, AHR, and airway smooth muscle mass in MA-challenged mice. While there were no differences in antioxidant capacity, persistent IL-4+ Th2 cell population suggests the MA model induces type 2 inflammation that is insensitive to corticosteroids. Our data indicate that chronic allergen exposure is associated with more persistent type 2 immune responses and corticosteroid insensitivity. Understanding differences between acute and chronic allergen models could unlock underlying mechanisms related to type 2-high severe asthma.


Early liver transplantation is indicated for tyrosinemia type I.
Liver transplantation is now accepted as the treatment of choice for tyrosinemia type I (hereditary tyrosinemia). In an effort to determine whether any factors in these patients would aid in predicting optimal timing of the transplant procedure, we evaluated several clinical, biochemical, and radiographic parameters in five successive patients undergoing liver transplant for tyrosinemia type I at the University of Minnesota. All five patients evidenced prolonged periods of clinical and metabolic stability with dietary therapy and four of five remained stable at the time of evaluation for transplantation. Nevertheless, all five suffered significant and unexpected complications of tyrosinemia prior to the time of liver transplant. Four developed renal stones, two were in liver failure, and one developed a neurologic crisis that left him completely paralyzed. Hepatocellular carcinoma was found in one of the five at transplant. We could identify no clinical, biochemical, or radiographic study that was predictive of the likelihood of significant complications of the disorder. Survival from the transplant procedure itself was 100%. The inability to predict or prevent significant complications of tyrosinemia and the favorable outcome from transplantation lead us to recommend liver transplant for all patients with tyrosinemia type I by 12 months of age.


Applied Methods to Assess the Antimicrobial Activity of Metallic-Based Nanoparticles.
With the rise of antibiotic resistance, the drive to discover novel antimicrobial substances and standard testing methods with the aim of controlling transmissive diseases are substantially high. In healthcare sectors and industries, although methods for testing antibiotics and other aqueous-based reagents are well established, methods for testing nanomaterials, non-polar and other particle-based suspensions are still debatable. Hence, utilities of ISO standard validations of such substances have been recalled where corrective actions had to be taken. This paper reports a serial analysis obtained from testing the antimicrobial activities of 10 metallic-based nanomaterials against 10 different pathogens using five different in vitro assays, where the technique, limitation and robustness of each method were evaluated. To confirm antimicrobial activities of metallic-based nanomaterial suspensions, it was found that at least two methods must be used, one being the agar well diffusion method, which was found to be the most reliable method. The agar well diffusion method provided not only information on antimicrobial efficacy through the size of the inhibitory zones, but it also identified antimicrobial ions and synergistic effects released by the test materials. To ascertain the effective inhibitory concentration of nanoparticles, the resazurin broth dilution method is recommended, as MIC can be determined visually without utilising any equipment. This method also overcomes the limit of detection (LoD) and absorbance interference issues, which are often found in the overexpression of cell debris and nanoparticles or quantum dots with optical profiles. In this study, bimetallic AgCu was found to be the most effective antimicrobial nanoparticle tested against across the bacterial (MIC 7 µg/mL) and fungal (MIC 62.5 µg/mL) species.


Use of Combined Uncertainty of Pesticide Residue Results for Testing Compliance with Maximum Residue Limits (MRLs).
The uncertainty of pesticide residue levels in crops due to sampling, estimated for 106 individual crops and 24 crop groups from residue data obtained from supervised trials, was adjusted with a factor of 1.3 to accommodate the larger variability of residues under normal field conditions. Further adjustment may be necessary in the case of mixed lots. The combined uncertainty of residue data including the contribution of sampling is used for calculation of an action limit, which should not be exceeded when compliance with maximum residue limits is certified as part of premarketing self-control programs. On the contrary, for testing compliance of marketed commodities the residues measured in composite samples should be greater than or equal to the decision limit calculated only from the combined uncertainty of the laboratory phase of the residue determination. The options of minimizing the combined uncertainty of measured residues are discussed. The principles described are also applicable to other chemical contaminants.


Atmospheric Degradation Initiated by OH Radicals of the Potential Foam Expansion Agent, CF3(CF2)2CH═CH2 (HFC-1447fz): Kinetics and Formation of Gaseous Products and Secondary Organic Aerosols.
The assessment of the atmospheric impact of the potential foam expansion agent, CF3(CF2)2CH═CH2 (HFC-1447fz), requires the knowledge of its degradation routes, oxidation products, and radiative properties. In this paper, the gas-phase reactivity of HFC-1447fz with OH radicals is presented as a function of temperature, obtaining kOH (T = 263-358 K) = (7.4 ± 0.4) × 10(-13)exp{(161 ± 16)/T} (cm(3)·molecule(-1)·s(-1)) (uncertainties: ±2σ). The formation of gaseous oxidation products and secondary organic aerosols (SOAs) from the OH + HFC-1447fz reaction was investigated in the presence of NOx at 298 K. CF3(CF2)2CHO was observed at low- and high-NOx conditions. Evidence of SOA formation (ultrafine particles in the range 10-100 nm) is reported with yields ranging from 0.12 to 1.79%. In addition, the absolute UV (190-368 nm) and IR (500-4000 cm(-1)) absorption cross-sections of HFC-1447fz were determined at room temperature. No appreciable absorption in the solar actinic region (λ > 290 nm) was observed, leaving the removal by OH radicals as the main atmospheric loss process for HFC-1447fz. The major contribution of the atmospheric loss of HFC-1447fz is due to OH reaction (84%), followed by ozone (10%) and chlorine atoms (6%). Correction of the instantaneous radiative efficiency (0.36 W m(-2)·ppbv(-1)) with the relatively short lifetime of HFC-1447fz (ca. 8 days) implies that its global warming potential at a time horizon of 100 year is negligible (0.19) compared to that of HCFC-141b (782) and to that of modern foam-expansion blowing agents (148, 882, and 804 for HFC-152a, HFC-245fa and HFC-365mfc, respectively).


Which mesh for hernia repair?
The concept of using a mesh to repair hernias was introduced over 50 years ago. Mesh repair is now standard in most countries and widely accepted as superior to primary suture repair. As a result, there has been a rapid growth in the variety of meshes available and choosing the appropriate one can be difficult. This article outlines the general properties of meshes and factors to be considered when selecting one. We performed a search of the medical literature from 1950 to 1 May 2009, as indexed by Medline, using the PubMed search engine (www.pubmed.gov). To capture all potentially relevant articles with the highest degree of sensitivity, the search terms were intentionally broad. We used the following terms: 'mesh, pore size, strength, recurrence, complications, lightweight, properties'. We also hand-searched the bibliographies of relevant articles and product literature to identify additional pertinent reports. The most important properties of meshes were found to be the type of filament, tensile strength and porosity. These determine the weight of the mesh and its biocompatibility. The tensile strength required is much less than originally presumed and light-weight meshes are thought to be superior due to their increased flexibility and reduction in discomfort. Large pores are also associated with a reduced risk of infection and shrinkage. For meshes placed in the peritoneal cavity, consideration should also be given to the risk of adhesion formation. A variety of composite meshes have been promoted to address this, but none appears superior to the others. Finally, biomaterials such as acellular dermis have a place for use in infected fields but have yet to prove their worth in routine hernia repair.


Clinical value of CA 15-3 for detection of distant metastases in newly diagnosed breast cancer.
The aim of the study is to investigate the clinical value of CA 15-3 for detection of distant metastases (DM) in newly diagnosed breast cancer. This retrospective study focuses on a population of 1,007 patients with locally advanced breast cancer (n=561) or metastatic breast cancer (n=446) diagnosed at the CGFL (Centre Georges Francois Leclerc) from March 1998 to October 2013. These patients underwent a measurement of CA 15-3 and an assessment of extension before any treatment. The cut-off value of CA 15-3 was determined and verified on two independents subpopulations determined in drawing lots. The ROC curve shows an AUC of 0.85 (p<0.0001). At the threshold of 50 kU/L, CA 15-3 before treatment has a predictive value on the existence of DM independently of the other prognostics factors. This predictive value has been found in every molecular subtype (AUC≥ 0.70; p≤ 0,085). The rate of false negative is of 38% and depends on the number and the type of the metastatic localization. Among the 28 patients without DM and a CA 15-3> 50 kU/L, 13 have developed DM and 11 died of cancer. In conclusion, these facts confirm the independently predictive value of CA 15-3 before treatment on the existence of DM and the complementarity of the marker with the assessment of extension by imagery.


Comparing the Resistance, Resilience, and Stability of Replicate Moving Bed Biofilm and Suspended Growth Combined Nitritation-Anammox Reactors.
Combined partial nitritation-anammox (PN/A) systems are increasingly being employed for sustainable removal of nitrogen from wastewater, but process instabilities present ongoing challenges for practitioners. The goal of this study was to elucidate differences in process stability between PN/A process variations employing two distinct aggregate types: biofilm [in moving bed biofilm reactors (MBBRs)] and suspended growth biomass. Triplicate reactors for each process variation were studied under baseline conditions and in response to a series of transient perturbations. MBBRs displayed elevated NH4+ removal rates relative to those of suspended growth counterparts over six months of unperturbed baseline operation but also exhibited significantly greater variability in performance. Transient perturbations led to strikingly divergent yet reproducible behavior in biofilm versus suspended growth systems. A temperature perturbation prompted a sharp reduction in NH4+ removal rates with no accumulation of NO2- and rapid recovery in MBBRs, compared to a similar reduction in NH4+ removal rates but a high level of accumulation of NO2- in suspended growth reactors. Pulse additions of a nitrification inhibitor (allylthiourea) prompted only moderate declines in performance in suspended growth reactors compared to sharp decreases in NH4+ removal rates in MBBRs. Quantitative fluorescence in situ hybridization demonstrated a significant enrichment of anammox in MBBRs compared to suspended growth reactors, and conversely a proportionally higher AOB abundance in suspended growth reactors. Overall, MBBRs displayed significantly increased susceptibility to transient perturbations employed in this study compared to that of suspended growth counterparts (stability parameter), including significantly longer recovery times (resilience). No significant difference in the maximal impact of perturbations (resistance) was apparent. Taken together, our results suggest that aggregate architecture (biofilm vs suspended growth) in PN/A processes exerts an unexpectedly strong influence on process stability.


Long-term corticosteroid therapy induces mild changes in trabecular bone texture.
The relative roles of bone mineral density (BMD) decrease and of microarchitectural changes in corticosteroid-induced osteoporosis (CIOP) are debated. Our objective has been to evaluate both bone microarchitecture (by a fractal analysis of texture on radiographs) and BMD in corticosteroid (CS)-treated patients. In this study, 60 patients from a rheumatology unit with a mean age of 60.6+/-14.8 years taking CS therapy for more than 6 months and a cumulative dose of prednisone over 1 g and 57 controls among age-matched patients and hospital staff were recruited. Bone diseases and bone-modifying drugs (except calcium, vitamin D, and hormonal replacement therapy [HRT]) were considered as exclusion criteria. A fractal analysis of trabecular bone texture was performed on calcaneus radiographs after an oriented analysis in 18 directions. The fractal analysis was based on the fractional Brownian motion model. Results were expressed by H parameter (H = 2 - fractal dimension) in each direction, Hmean being the average of 18 directions, Hmini the minimum, and Hmaxi the maximum. BMD was measured by double-energy X-ray absorptiometry (DEXA) at the femoral neck (FN) and lumbar spine (LS). The odds ratios (OR) were calculated for a variation of 1 SD. The mean duration and dose of CS therapy was 5.6+/-6.6 years and 16.9+/-19.7 g. CS therapy was significantly correlated to a decrease in FN or LSBMD: OR = 1.95, 95% confidence interval (CI, 1.29-2.97) and OR = 3.19 (CI, 1.80-5.66), respectively. The Hmean and Hmaxi were significantly lower in the cases than in the controls: P = 0.03 and P = 0.02; OR = 1.67 (CI, 1.10-2.54) and OR = 1.75 (CI, 1.05-2.37). A similar trend was observed with Hmini but the difference did not reach the level of statistical significance: P = 0.06, OR = 1.57 (CI, 1.05-2.37). This study was repeated among cases and controls who had never taken HRT (respectively, n = 40 and n = 39). The results were similar. Among patients taking CS therapy, the presence of nontraumatic fractures was inversely related to BMD values but not to texture parameters. These data have shown that long-term CS therapy induces both BMD decrease and trabecular bone texture changes. The effect of CS therapy was much stronger on BMD than on the fractal H parameter. These results are in accordance with previous studies showing a lower effect of CS therapy on bone microarchitecture than on bone mass. These results can be contrasted with those observed in women with postmenopausal osteoporosis and vertebral crush fractures in which the variations in the fractal parameters are more significant than the BMD variations.


Applications and advantages of virus-induced gene silencing for gene function studies in plants.
Virus-induced gene silencing (VIGS) is a recently developed gene transcript suppression technique for characterizing the function of plant genes. The approach involves cloning a short sequence of a targeted plant gene into a viral delivery vector. The vector is used to infect a young plant, and in a few weeks natural defense mechanisms of the plant directed at suppressing virus replication also result in specific degradation of mRNAs from the endogenous plant gene that is targeted for silencing. VIGS is rapid (3-4 weeks from infection to silencing), does not require development of stable transformants, allows characterization of phenotypes that might be lethal in stable lines, and offers the potential to silence either individual or multiple members of a gene family. Here we briefly review the discoveries that led to the development of VIGS and what is known about the experimental requirements for effective silencing. We describe the methodology of VIGS and how it can be optimized and used for both forward and reverse genetics studies. Advantages and disadvantages of VIGS compared with other loss-of-function approaches available for plants are discussed, along with how the limitations of VIGS might be overcome. Examples are reviewed where VIGS has been used to provide important new insights into the roles of specific genes in plant development and plant defense responses. Finally, we examine the future prospects for VIGS as a powerful tool for assessing and characterizing the function of plant genes.


From railway spine to whiplash--the recycling of nervous irritation.
The search for a specific structural basis for chronic whiplash and other chronic pain and fatigue syndromes has been in progress for decades, and yet currently there remains no "structural" solution to these enigmata. In light of the failure of research to identify the chronic "damage" or pathology as lying in a muscular, bony, or "connective tissue" sites for many chronic pain syndromes like whiplash, fibromyalgia, et cetera, more recent attention has been paid to nervous system structures. Nerve irritation has been implicated as the basis for the pain and other symptoms that are common to many chronic disability syndromes. We postulate here, however, that the concept of nervous irritation has been prostituted for centuries whenever more concrete structural explanations for chronic pain and other controversial illness have been untenable. We suggest that, after each cycle of nervous irritation as a disease, and subsequent dismissal of the notion, the doctrine of irritation as a disease was too good to go away. First, with the hypersthenic and asthenic diseases of the nineteenth century, then railway spine, whiplash, thoracic outlet syndrome, and now brachial plexus irritation, we detect the same pattern: patients with symptoms, but no objective evidence of nerve disease. Nervous irritation has repeatedly served this purpose for the last 200 years. It is our intent that bringing an understanding of this trend will encourage current clinicians and researchers to appreciate the need to abandon this form of speculation without historical insight when dealing with today's controversial syndromes.