Electric nerve stimulation (ENS): 70 clinical cases of bi-block aided by an electric bipolar signal.
The practice of local anaesthesia aided by ENS, among other things, is based on the use of available electric signals searching peripheral nerves. Most electric generators produce a square monopolar signal that is potentially dangerous because it exists a risk of hyperpolarization damage with neural lesions by galvanic effect. To inform about the use of a bipolar signal, different than the usual square monophasic signal. In theory a bipolar signal prevents the risk of hyperpolarization by lessening average intensity of current crossing the tissues. Our experience is based on 70 clinical cases of bi-block performed by searching the nerve by using an electric bipolar signal to locate a peripheral nerve. Local anaesthesia can be successfully performed by using bipolar electric signals not currently employed. In 2/70 patients it was needed to perform surgery under general anesthesia. The rate of successful blocks was similar to the results of current literature. Most authors search peripheral nerves by square monophasic signals. It arrives because it's widely believed that a square signal is advantageous because of high ratio di/dt (intensity/time). Today, it's not assessed in clinical practice that an electric signal is deeply modified in its parameters and its form by capacitive and resistive properties of the human body.


Thermodynamic and Kinetic Requirements in Anaerobic Methane Oxidizing Consortia Exclude Hydrogen, Acetate, and Methanol as Possible Electron Shuttles.
Anaerobic methane oxidation (AMO) has long remained an enigma in microbial ecology. In the process the net reaction appears to be an oxidation of methane with sulfate as electron acceptor. In order to explain experimental data such as effects of inhibitors and isotopic signals in biomarkers it has been suggested that the process is carried out by a consortium of bacteria using an unknown compound to shuttle electrons between the participants. The overall change in free energy during AMO with sulfate is very small (?22 kJ mol-1) at in situ concentrations of methane and sulfate. In order to share the available free energy between the members of the consortium, the concentration of the intermediate electron shuttle compound becomes crucial. Diffusive flux of a substrate (i.e, the electron shuttle) between bacteria requires a stable concentration gradient where the concentration is higher in the producing organism than in the consuming organism. Since changes in concentrations cause changes in reaction free energies, the diffusive flux of a catabolic product/substrate between bacteria is associated with a net loss of available energy. This restricts maximal inter-bacterial distances in consortia composed of stationary bacteria. A simple theoretical model was used to describe the relationship between inter-bacterial distances and the energy lost due to concentration differences in consortia. Key parameters turned out to be the permissible concentration range of the electron shuttle in the consortium (i.e., the concentration range that allows both participants to gain sufficient energy) and the stoichiometry of the partial reactions. The model was applied to two known consortia degrading ethanol and butyrate and to four hypothetical methane-oxidizing consortia (MOC) based on interspecies transfer of hydrogen, methanol, acetate, or formate, respectively. In the first three MOCs the permissible distances between producers and consumers of the transferred compounds were less than two times prokaryotic cell wall diameters. Consequently, it is not possible that a MOC can be based on inter-species transfer of hydrogen, methanol, or acetate. Formate, on the other hand, is a possible shuttle candidate provided the bacteria are attached to one another. In general the model predicts that members of consortia thriving on low energy such as the MOC must adhere to each other and utilize a compound for the exchange of electrons that has a high permissible concentration range and a high diffusion coefficient and transfers as many electrons as possible per molecule.


Invasive versus non-invasive mapping of the motor cortex.
Precise and comprehensive mapping of somatotopic representations in the motor cortex is clinically essential to achieve maximum resection of brain tumours whilst preserving motor function, especially since the current gold standard, that is, intraoperative direct cortical stimulation (DCS), holds limitations linked to the intraoperative setting such as time constraints or anatomical restrictions. Non-invasive techniques are increasingly relevant with regard to pre-operative risk-assessment. Here, we assessed the congruency of neuronavigated transcranial magnetic stimulation (nTMS) and functional magnetic resonance imaging (fMRI) with DCS. The motor representations of the hand, the foot and the tongue regions of 36 patients with intracranial tumours were mapped pre-operatively using nTMS and fMRI and by intraoperative DCS. Euclidean distances (ED) between hotspots/centres of gravity and (relative) overlaps of the maps were compared. We found significantly smaller EDs (11.4 ± 8.3 vs. 16.8 ± 7.0 mm) and better spatial overlaps (64 ± 38% vs. 37 ± 37%) between DCS and nTMS compared with DCS and fMRI. In contrast to DCS, fMRI and nTMS mappings were feasible for all regions and patients without complications. In summary, nTMS seems to be the more promising non-invasive motor cortex mapping technique to approximate the gold standard DCS results.


Dynamic chemical characteristics of soil solution after pig manure application: a column study.
When manures from intensive livestock operations are applied to agricultural or vegetable fields at a high rate, large amounts of salts and metals will be introduced into soils. Using a column leaching experiment, this study assessed the leaching potential of the downward movement of Cu and Zn as well as some salt ions after an intensive farm pig manure at rates of 0%, 5% and 10% (w/w) were applied to the top 20 cm of two different textured soils (G soil -sandy loam soil; H soil-silty clay loam soil), and investigated the growth of amaranth and Cu and Zn transfer from soil to amaranth (Amaranthus tricolor). Soil solutions were obtained at 20, 40 and 60 cm depth of the packed column and analyzed for pH, electrical conductivity (EC), dissolved organic matter (DOC) and Cu and Zn concentrations. The results indicated that application of pig manure containing Cu and Zn to sandy loam soil might cause higher leaching and uptake risk than silty clay loam soil, especially at high application rates. And manure amendment at 5% and 10% significantly decreased the biomass of amaranth, in which the salt impact rather than Cu and Zn toxicity from manures played more important role in amaranth growth. Thus the farmer should avoid application the high rate of pig manure containing metal and salt to soil at a time, especially in sandy soil.


Comparison of Surveillance of Surgical Site Infections by a National Surveillance Program and by Institutional Audit.
Reported incidence of surgical site infections (SSI) after colonic surgery varies widely. These variations depend not only on patient- and surgery-related parameters but are influenced by type and quality of follow-up. The aim of the study was to compare SSI assessed by two independent prospective surveillance systems, a national surveillance program based on recommendations of the National Healthcare Safety Network (Swissnoso) versus an international audit system, the ERAS® Interactive Audit System (EIAS; Encare, Stockholm, Sweden). Comparative study of a consecutive cohort of colonic resections at a single institution from September 2015 to March 2017. Independent prospective SSI monitoring was available from Swissnoso and EIAS. Inter-observer reliability was calculated using Cohen k. Sensitivity, specificity, and accuracy of EIAS in assessing SSI was compared with Swissnoso, considered as gold standard. The final sample included 143 patients. Of these, 136 (95.1%) were classified into the same category by both systems, identifying 17 patients (12.5%) with SSI and 119 patients (87.5%) without SSI, respectively. Discrepant results were found for the remaining seven patients (4.9%) with four SSI categorization according to Swissnoso but not EIAS, and three SSI categorization in EIAS but not in Swissnoso; all miscategorized patients presented superficial SSI. Sensitivity, specificity, and accuracy of EIAS for SSI recording was 81%, 97.5%, and 95.1%, respectively. Inter-observer agreement was high (Cohen k value of 0.801, p < 0.001). Case-by-case analysis of discrepant findings revealed mainly discrepant interpretation of clinical symptoms and erroneous labeling of non-procedure-related infections. Surgical site infection recording by two independent systems showed high concordance and good inter-rater reliability.


Prognosis and treatment of T1G3 bladder tumours. A prognostic factor analysis of 121 patients. Dutch South Eastern Bladder Cancer Study Group.
Patients with T1G3 bladder cancer have a considerable risk for recurrence and/or progressive disease. Until now no consensus has been achieved on the optimal treatment. Within the Dutch South Eastern Bladder Cancer Study Group, 155 patients with a T1G3 bladder tumour were seen between 1983 and 1988. After review of histology, 121 could be evaluated and recurrence-free interval was studied with regard to prognostic factors. Prognostic factors such as sex, age, blood group, abnormalities on intravenous urography, pretreatment tumour configuration, number of tumours, number of locations involved in the bladder, voided urine cytology, results of random biopsies and mitotic index were evaluated, using a multivariate analysis with the Cox proportional hazard model. During the follow-up period, 70 (58%) patients had recurrent bladder cancer, and of these 30 (43%) had progression into invasive disease. Of the possible prognostic factors analysed, only multiplicity (P = 0.03) and the number of locations of the tumours (P = 0.03) were independent prognostic factors in relation to the risk of recurrence. The recurrence-free interval was influenced by the therapy. For T1G3 tumours, additional intravesical immunotherapy/chemotherapy or radiotherapy after transurethral resection (TUR) increased the recurrence-free interval significantly. Because most other parameters did not show additional prognostic value, the T1G3 tumours can be considered as homogeneous with regard to prognosis. Only multiplicity and the number of locations involved added to the prognostic significance of patients with these bladder tumours. In addition, it is advisable to give patients with T1G3 tumours additional treatment after the initial TUR.


Plugging interactions of HAP2 pentamer into the distal end of flagellar filament revealed by electron microscopy.
Bacterial flagellum has a cap structure tightly attached to its distal end. The cap is an oligomeric assembly of HAP2 protein (also called FliD) and plays an essential role in the filament growth in vivo by preventing flagellin monomers from leaking out without polymerization. Electron micrographs of the HAP2 complex formed in solution showed exclusively a pentagonal shape, called "star-cap", which was thought to be the end-on view of the cap. The molecular mass roughly corresponded to a dodecamer of HAP2, and therefore a double-layered star-cap was modeled to be the cap. Here, we have observed the side view of the complex in electron micrographs. The images clearly show a rectangular shape, about 80 A wide and 180 A long, with a bipolar feature in its long axis, indicating that the complex is a bipolar pair of pentamers. A thin plate feature is identified at each end of the particle, which looks exactly like the one observed as the structure of the native filament cap. Together with the structure of the filament previously analyzed by electron cryomicroscopy, the results suggest that the cap is a pentamer with its thin plate exposed to the solvent and the other half plugged into the hole at the distal end of the filament, which is almost twice wider than its central channel. This also allows us to model the axial domain arrangement of flagellin subunit in the filament.


Spheno-Orbital Meningiomas: An Analysis Based on World Health Organization Classification and Ki-67 Proliferative Index.
To evaluate the clinical behavior of spheno-orbital meningiomas with regard to World Health Organization (WHO) tumor grade and Ki-67, a cellular marker of proliferation. A retrospective review over a 16-year period of the demographic, clinical, radiographic, and surgical data of all patients with spheno-orbital meningioma who underwent surgical resection. Tumor specimens were examined histologically using the current WHO 2016 classification and immunohistochemically using Ki-67/MIB-1 monoclonal antibody. Thirty-eight patients met all inclusion criteria: 78.9% of tumors were WHO grade I with a mean Ki-67 of 3.76, and 93% of patients were clinically stable at last follow up; 10.5% of lesions were WHO grade II (atypical) with a mean Ki-67 of 14.93, and 10.5% of lesions were WHO grade III (anaplastic) with a mean Ki-67 of 58.3. All grade II and III meningiomas exhibited an aggressive clinical course. There were statistically significant correlations between disease clinical progression and WHO tumor grade (p < 0.001), between disease clinical progression and Ki-67 (p < 0.001), and between increasing Ki-67 index and higher WHO grade (p < 0.001). For WHO grade I lesions, a Ki-67 of ≥3.3 correlated with recurrence (p = 0.0256). Overall, disease-specific mortality occurred in 5 (13%) patients. Ki-67 index is a valuable marker to use in conjunction with WHO grade to predict meningioma behavior, particularly in histologically borderline lesions, and possibly to identify a subset of WHO grade I tumors at risk of recurrence. This combination of methods can aid in tailoring treatment and surveillance strategies.


Label-Free Biological and Chemical Sensing Using Whispering Gallery Mode Optical Resonators: Past, Present, and Future.
Sensitive and rapid label-free biological and chemical sensors are needed for a wide variety of applications including early disease diagnosis and prognosis, the monitoring of food and water quality, as well as the detection of bacteria and viruses for public health concerns and chemical threat sensing. Whispering gallery mode optical resonator based sensing is a rapidly developing field due to the high sensitivity and speed of these devices as well as their label-free nature. Here, we describe the history of whispering gallery mode optical resonator sensors, the principles behind detection, the latest developments in the fields of biological and chemical sensing, current challenges toward widespread adoption of these devices, and an outlook for the future. In addition, we evaluate the performance capabilities of these sensors across three key parameters: sensitivity, selectivity, and speed.


Successful pregnancy after natalizumab-associated progressive multifocal leukoencephalopathy in a patient with multiple sclerosis.
We report the case of a post-progressive multifocal leukoencephalopathy (PML), multiple sclerosis (MS) patient with an uncomplicated pregnancy and delivery. A 28-year-old woman on natalizumab (total of 49 infusions) was diagnosed with PML due to typical magnetic resonance imaging (MRI) and clinical presentation. John Cunningham virus (JCV) was detected in the cerebrospinal fluid (CSF) during the immune reconstitution inflammatory syndrome (IRIS). Nine months after PML onset, JCV negativity in the CSF was observed. MS was stabilised with dimethyl fumarate (DMF), and 18 months later, a desired pregnancy was reported, resulting in the birth of a healthy boy. Our report gives new hope regarding family planning for post-PML patients.


Supramolecular Assembly of pH-Sensitive Triphenylene Derived π-Gelators and Their Application as Molecular Template for the Preparation of Silica Nanotubes.
The gelation properties and mode of self-assembly of six asymmetrical hexaether triphenylene derivatives mono-functionalized with carboxylic and primary amine groups were investigated. The presence of a carboxylic and amine group attached to the triphenylene core generated stable, thermo- and pH-sensitive supramolecular π-organogels with a reversible response to both stimuli. In order to understand the gelation process, we studied the effect of the spacer length and found a different gelation scope for the acid and basic derivatives that accounts for a different supramolecular self-assembly. The presence of the basic group on the amino derivatives was used to guide and catalyze the templated in situ sol-gel polymerization of TEOS and allowed us, under controlled hydrolytic conditions, to prepare an entangled fibrillar network of silica nanotubes.


Serial alterations in digital hemodynamics and endothelin-1 immunoreactivity, platelet-neutrophil aggregation, and concentrations of nitric oxide, insulin, and glucose in blood obtained from horses following carbohydrate overload.
To quantify changes in endothelium-derived factors and relate those changes to various aspects of digital hemodynamics during the prodromal stages of carbohydrate overload (CHO)-induced laminitis in horses. 20 adult horses without abnormalities of the digit. Digital and jugular venous blood samples were collected at 1-hour intervals (for assessment of endothelin-1 [ET-1] immunoreactivity and measurement of glucose, insulin, and nitric oxide [NO] concentrations) or 4-hour intervals (CBC and platelet-neutrophil aggregate assessment) for 8 hours or 16 hours after induction of CHO-associated laminitis in horses treated with an ET-1 antagonist. Effects of treatment, collection site, and time and the random effects of horse on each variable were analyzed by use of a repeated-measures model. Where treatment and collection site had no significant effect, data were combined. Compared with baseline values, CHO resulted in changes in several variables, including a significant increase from baseline in digital blood ET-like immunoreactivity at 11 hours; digital blood ET-like immunoreactivity was significantly greater than that in jugular venous blood at 8, 9, 11, and 12 hours. Digital and jugular venous blood concentrations of glucose increased from baseline significantly at 3, 4, and 5 hours; insulin concentration increased significantly at 5 hours; and the number of platelet-neutrophil aggregates increased significantly at 12 hours. In horses, concurrent increases in venous blood ET-1 immunoreactivity, insulin and glucose concentrations, and platelet-neutrophil aggregates support a role of endothelial dysfunction in the pathogenesis of CHO-induced laminitis.


Hybrid metal-Cu2S nanostructures as efficient co-catalysts for photocatalytic hydrogen generation.
In this communication, we present a new synthesis method for the fabrication of hybrid metal-Cu2S (M = Pt, FePt) nanocrystals (HNs). The metal-Cu2S HNs were investigated in photocatalytic hydrogen generation as effective co-catalysts on TiO2. The Pt-Cu2S/TiO2 catalyst showed a higher hydrogen generation rate compared with a pure TiO2 catalyst. This enhancement is attributed to the synergistic effects between Cu2S and Pt, which significantly improve the light absorption ability and the charge separation activity.


Diffusive dynamics on multidimensional rough free energy surfaces.
The dynamics of processes relevant to chemistry and biophysics on rough free energy landscapes is investigated using a recently developed algorithm to solve the Smoluchowski equation. Two different processes are considered: ligand rebinding in MbCO and protein folding. For the rebinding dynamics of carbon monoxide (CO) to native myoglobin (Mb) from locations around the active site, the two-dimensional free energy surface (FES) is constructed using extensive molecular dynamics simulations. The surface describes the minima in the A state (bound MbCO), CO in the distal pocket and in the Xe4 pocket, and the transitions between these states and allows to study the diffusion of CO in detail. For the folding dynamics of protein G, a previously determined two-dimensional FES was available. To follow the diffusive dynamics on these rough free energy surfaces, the Smoluchowski equation is solved using the recently developed hierarchical discrete approximation method. From the relaxation of the initial nonequilibrium distribution, experimentally accessible quantities such as the rebinding time for CO or the folding time for protein G can be calculated. It is found that the free energy barrier for CO in the Xe4 pocket and in the distal pocket (B state) closer to the heme iron is approximately 6 kcal/mol which is considerably larger than the inner barrier which separates the bound state and the B state. For the folding of protein G, a barrier of approximately 10 kcal/mol between the unfolded and the folded state is consistent with folding times of the order of milliseconds.


Futility, the Multiorganization Policy Statement, and the Schneiderman Response.
This essay offers a brief history of futility, in both sociocultural and medical contexts, with some personal reflection on the disappearance and reappearance of medical futility during the author's 40-plus years in medicine. It discusses the creation of the Texas Advance Directives Act (TADA), which, even with its flaws, creates the only legal safe harbor for physicians engaged in futility disputes. It also offers reflection on the commendable Multiorganization Policy Statement on "potentially inappropriate treatment" yet comes to the same conclusion as Schneiderman. The words recommended for use in futility disputes are not helpful in facing these disputes. Medical futility appropriately understood transcends pure physiologic, quantitative, or qualitative concepts. Those who seek to help resolve futility disputes must take into account not only these concepts, but also emotional, social, and spiritual factors as well. If we are to collectively face the challenge of medical futility, we must cultivate a more covenantal and communitarian ethical framework, develop processes similar to TADA in other state laws, and teach that the acceptance of finitude does not reduce the sacred value of life.


Ribosomal ribonucleic acid similarities in the classification of Rhodococcus and related taxa.
Duplexes were prepared between 14C-labelled rRNA from both Rhodococcus equi C7 and Rhodococcus rhodochrous N54 and DNA from 16 actinomycetes representing the genera Rhodococcus, Mycobacterium, Nocardia, Saccharopolyspora and Streptomyces. The relationships between the organisms were determined by plotting the temperature at which 50% of the duplex was denatured (Tm(e)) against the percentage of rRNA binding (microgram 14C-labelled rRNA duplexed per 100 micrograms filter-bound DNA). All of the strains formed stable duplexes but each organism occupied a definite area on the rRNA similarity map. All of the organisms share a close phylogenetic relationship but representatives of the genera Rhodococcus, Mycobacterium, Nocardia and Streptomyces fell into four recognizable clusters on the similarity map. These data support and extend current trends in the classification of Rhodococcus and allied taxa. The guanine plus cytosine content of the DNA from the test strains was within the range 69.3 to 76.9 mol %.


Finite-size scaling for critical conditions for stable quadrupole-bound anions.
We present finite-size scaling calculations of the critical parameters for binding an electron to a finite linear quadrupole field. This approach gives very accurate results for the critical parameters by using a systematic expansion in a finite basis set. The model Hamiltonian consists of a charge Q located at the origin of the coordinates and k charges -Q/k located at distances R(i), i=1, em leader,k. After proper scaling of distances and energies, the rescaled Hamiltonian depends only on one free parameter q=QR. Two different linear charge configurations with q>0 and q<0 are studied using basis sets in both spherical and prolate spheroidal coordinates. For the case with q>0, the finite size scaling calculations give an extrapolated critical value of q(c)=1.469 70+/-0.000 05 a.u. by using a basis set with prolate spheroidal coordinates. For the quadrupole case with q<0, we obtained an extrapolated critical value of mid R:q(c)mid R:=3.982 51+/-0.000 01 a.u. for stable quadrupole bound anions. The corresponding critical exponent for the ground state energy alpha=1.9964+/-0.0005, with E approximately (q-q(c))(alpha).


Intermediate scattering function for macromolecules in solutions probed by neutron spin echo.
The neutron-spin-echo method (NSE) is a powerful technique for studying internal dynamics of macromolecules in solutions because it can simultaneously probe length and time scales comparable to intramolecular density fluctuations of macromolecules. Recently, there has been increased, strong interest in studying protein internal motions using NSE. The coherent intermediate scattering function (ISF) measured by NSE depends on internal, rotational, and translational motions of macromolecules in solutions. It is thus critical, but highly nontrivial, to separate the internal motion from other motions in order to properly understand protein internal dynamics. Even though many experiments are performed at relatively high concentrations, current theories of calculating the ISF of concentrated protein solutions are either inaccurate or flawed by incorrect assumptions for realistic protein systems with anisotropic shapes. Here, a theoretical framework is developed to establish the quantitative relationship of different motions included in the ISF. This theory based on the dynamic decoupling approximation is applicable to a wide range of protein concentrations, including dilute cases. It is also, in general, useful for studying many other types of macromolecule systems studied by NSE.


Novel nonviral bioassays for mouse type I and type III interferon.
We used embryo fibroblasts from Mx2-Luc transgenic mice that express Firefly luciferase under control of the interferon (IFN)-regulated mouse Mx2 promoter to develop simple nonviral bioassays for type I and type III IFN. Since type III IFN is acid-labile, Mx2-Luc fibroblasts detected the presence of type I IFN in acid-treated biological samples with high sensitivity and selectivity. For selective detection of type III IFN, we employed embryo fibroblasts from Mx2-Luc mutant mice that lack functional receptors for type I IFN. The sensitivity of this latter assay remained comparatively low, presumably because type III IFN receptors are not abundantly present on fibroblasts. The main advantages of our novel IFN assays are that they are easy to perform, yield fast results, and can be used in laboratories that are not licensed for work with infectious agents. Further, the type I IFN assay has superior sensitivity than commercially available enzyme-linked immunosorbent assay systems.


The excluded philosophy of evo-devo? Revisiting C.H. Waddington's failed attempt to embed Alfred North Whitehead's "organicism" in evolutionary biology.
Though a prominent British developmental biologist in his day, a close friend of Theodosius Dobzhansky, and a frequent correspondent with Ernst Mayr, C.H. Waddington did not enter the ranks of "architect" of the Modern Synthesis. By the end of his career, in fact, he recognized that other biologists reacted to his work "as though they feel obscurely uneasy"; and that the best that some philosophers of biology could say of his work was that he was not "wholly orthodox" (Waddington 1975c, 11). In this essay, I take Waddington's self-assessments at face value and explore three potential reasons why his work did not have more of a direct impact: Waddington's explicit support for the philosophy of Alfred North Whitehead; a lack of institutional support; and Waddington's occasional marginalization from the core network of American neo-Darwinians. Though excluded from the Modern Synthesis in the mid-20th century, it now appears that Waddington's work does undergird the emerging evo-devo synthesis. Whether this indicates concomitant, if implicit, support for Whiteheadian philosophy is an interesting question not explored here.


Failure of oral water loading and intravenous hypotonic saline to suppress plasma prolactin in man.
To test the effect of acute changes in plasma osmolality on plasma prolactin concentrations, the hormone was measured before and during oral water loading, hypotonic saline infusion, and hypertonic saline infusion in normal subjects. In 10 normal men there was a small but statistically significant rise in mean prolactin, from 7.6 to 12.3 ng/ml, occurring within half an hour after the ingestion of a water load of 20 ml/kg. A small but statistically insignificant rise in mean plasma prolactin was observed in 11 normal women, although there was a significant negative correlation between plasma prolactin and plasma osmolality in these subjects. No effect of the intravenous infusion of either hypotonic saline (0.45%) or hypertonic saline (5%) on mean plasma prolactin was noted in 5 normal men. These studies do not confirm a previously reported suppression of prolactin concentrations by oral water loading of hypotonic saline infusions in normal subjects. While the data suggest a negative correlation between plasma osmolality and plasma prolactin, at least after water loading, they do not support a physiological role for prolactin in the short-term regulation of plasma osmolality in humans.


Tuning of crystallization method and ligand conformation to give a mononuclear compound or two-dimensional SCO coordination polymer based on a new semi-rigid V-shaped bis-pyridyl bis-amide ligand.
With the new semi-rigid V-shaped bidentate pyridyl amide compound 5-methyl-N,N'-bis(pyridin-4-yl)benzene-1,3-dicarboxamide (L) as an auxiliary ligand and the FeII ion as the metal centre, one mononuclear complex, bis(methanol-κO)bis[5-methyl-N,N'-bis(pyridin-4-yl)benzene-1,3-dicarboxamide-κN]bis(thiocyanato-κN)iron(II), [Fe(SCN)2(C19H16N4O2)2(CH3OH)2] (1), and one two-dimensional coordination polymer, catena-poly[[[bis(thiocyanato-κN)iron(II)]-bis[μ-5-methyl-N,N'-bis(pyridin-4-yl)benzene-1,3-dicarboxamide-κ2N:N']] methanol disolvate dihydrate], {[Fe(SCN)2(C19H16N4O2)2]·2CH3OH·2H2O}n (2), were prepared by slow evaporation and H-tube diffusion methods, respectively, indicating the effect of the method of crystallization on the structure type of the target product. Both complexes have been structurally characterized by elemental analysis, IR spectroscopy and single-crystal X-ray crystallography. The single-crystal X-ray diffraction analysis shows that L functions as a monodentate ligand in mononuclear 1, while it coordinates in a bidentate manner to two independent Fe(SCN)2 units in complex 2, with a different conformation from that in 1 and the ligands point in two almost orthogonal directions, therefore leading to a two-dimensional grid-like network. Investigation of the magnetic properties reveals the always high-spin state of the FeII centre over the whole temperature range in 1 and a gradual thermally-induced incomplete spin crossover (SCO) behaviour below 150 K in 2, demonstrating the influence of the different coordination fields on the spin properties of the metal ions. The current results provide useful information for the rational design of functional complexes with different structure dimensionalities by employing different conformations of the ligand and different crystallization methods.


Enantioselective analysis of ofloxacin enantiomers by partial-filling capillary electrophoresis with bacteria as chiral selectors.
The enantiomeric separation of ofloxacin enantiomers (OFLX) was achieved by using capillary electrophoresis partial-filled with Escherichia coli, Pseudomonas aeruginosa (Gram-negative), and Staphylococcus aureus (Gram-positive) as chiral selectors. Experimental parameters, including the concentration of background electrolyte, applied voltage, length of the filled bacteria plug, and pH of the buffer, were intensively investigated. Baseline separation of OFLX could be achieved within 7 min by using E. coli and P. aeruginosa as chiral selectors under the following conditions: electrophoretic buffer composed of 10 mM phosphate buffer at pH 7.4, applied voltage at 15 kV, and the bacteria (6.0 × 10(8) cells/mL) were injected into the capillary by gravity with injection height of 17.5 cm for 180 s (E. coli), 300 s (P. aeruginosa), and 300 s (S. aureus), respectively. E. coli and P. aeruginosa had better chiral selectivity for OFLX than S. aureus, which was in good agreement with OFLX having better antimicrobial activity on Gram-negative rather than Gram-positive bacteria. A novel method was developed for the enantioselective separation of enantiomers using bacteria as chiral selectors, which provides a new approach for antimicrobials enantioselective analysis, chiral pharmacodynamics, and chiral pharmacokinetics studies.


Selection of genetically encoded fluorescent single domain antibodies engineered for efficient expression in Escherichia coli.
Genetically encoded fluorescent antibodies are desirable for many applications in biotechnology and proteomics. However, the efficient production of single chain antibodies fused to fluorescent proteins like green fluorescent protein is still a major challenge. This is due to the opposite redox requirements of recombinant antibodies and fluorescent proteins for proper folding. To overcome this obstacle, we designed a novel strategy to directly select functional fluorescent antibodies (fluobodies) engineered for efficient cytosolic expression in Escherichia coli, starting from a llama heavy chain antibody (VHH) library. We used this strategy to produce several VHH fluobodies directed against microtubules. After biochemical characterization in vitro, we used a selected fluobody as a convenient biomarker of the microtubule cytoskeleton in eukaryotic cells and engineered its properties. This work provides a reliable approach for the production of fluobodies in wild-type E. coli and furthermore suggests that fusions of recombinant VHH with other cytosolic proteins are now possible, creating new opportunities for biotechnology and biomedical research.


The Drosophila maternal-effect mutation grapes causes a metaphase arrest at nuclear cycle 13.
grapes (grp) is a second chromosome (36A-B) maternal-effect lethal mutation in Drosophila melanogaster. We demonstrate that the syncytial nuclear divisions of grp-derived embryos are normal through metaphase of nuclear cycle 12. However, as the embryos progress into telophase of cycle 12, the microtubule structures rapidly deteriorate and midbodies never form. Immediately following the failure of midbody formation, sister telophase products collide and form large tetraploid nuclei. These observations suggest that the function of the midbody in the syncytial embryo is to maintain separation of sister nuclei during telophase of the cortical divisions. After an abbreviated nuclear cycle 13 interphase, these polyploid nuclei progress through prophase and arrest in metaphase. The spindles associated with the arrested nuclei are stable for hours even though the microtubules are rapidly turning over. The nuclear cycle 13 anaphase separation of sister chromatids never occurs and the chromosomes, still encompassed by spindles, assume a telophase conformation. Eventually neighboring arrested spindles begin to associate and form large clusters of spindles and nuclei. To determine whether this arrest was the result of a disruption in normal developmental events that occur at this time, both grp-derived and wild-type embryos were exposed to X-irradiation. Syncytial wild-type embryos exhibit a high division error rate, but not a nuclear-cycle arrest after exposure to low doses of X-irradiation. In contrast, grp-derived embryos exhibit a metaphase arrest in response to equivalent doses of X-irradiation. This arrest can be induced even in the early syncytial divisions prior to nuclear migration. These results suggest that the nuclear cycle 13 metaphase arrest of unexposed grp-derived embryos is independent of the division-cycle transitions that also occur at this stage. Instead, it may be the result of a previously unidentified feedback mechanism.


Current and future issues in assisted reproduction.
The last quarter of the twentieth century has given rise to reproductive technologies and arrangements that in the earlier part of the century could only be dreamed of by the authors of science fiction. We stand in the middle of this reproductive revolution, trying to cope with the developments that have already occurred but with an uneasy sense that the future may be even more complicated ethically than the past and the present. In this brief essay, I will survey recent ethical and public-policy discussions of two reproductive techniques (assisted insemination and in vitro fertilization) and one reproductive arrangement (surrogate motherhood). After distinguishing three phases in the normative debate, I will briefly comment on some of the characteristics of, and continuing ambiguities in, the ethical debate of the past 25 years. At the conclusion of the essay, I will attempt to anticipate three future issues in ethics and reproduction.


Perceived Teacher Autonomy Support and Students' Deep Learning: The Mediating Role of Self-Efficacy and the Moderating Role of Perceived Peer Support.
The purpose of this research is to test the mediation effect of self-efficacy on college student's perception of teacher autonomy support and students' deep learning, and whether the peer support perceived by students can moderate the relationship between perceived teacher autonomy support and deep learning. A survey of 1,800 college students from a provincial undergraduate normal university in Guizhou Province in China was conducted through the revised Perceived Teacher Autonomy Support Scale, Deep Learning Scale, Self-Efficacy Scale, and Perceived Peer Support Scale (Mean age = 21 years old, SD = 1.34). Data use SPSS23.0, AMOS22.0 for descriptive analysis and correlation analysis, exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), moderation effect, and mediation effect analysis. The research results show that after controlling for gender, major, and grade, self-efficacy partially moderates the connection between perceived teacher autonomy support and deep learning of college students. Moreover, perceived peer support mediates the relationship between perceived teacher autonomy support and students' self-efficacy.


The impact of informative tutoring feedback and self-efficacy on motivation and achievement in concept learning.
Informative tutoring feedback (ITF) provides assisted multiple response tries by offering strategically useful information for task completion as opposed to simply offering the solution. Previous studies on ITF focused on its effects on achievement. The present studies examine the assumption that ITF affects not only achievement, but also motivational variables such as task engagement, effort, persistence, and satisfaction with performance. In two experiments, students differing in self efficacy (SE) for identifying concepts worked on concept identification tasks. In cases of incorrect hypothesis about the concept, they received either outcome feedback or ITF. Results reveal that motivation and achievement depend on both SE and type of feedback. Future research should examine in more detail how ITF affects the self-enhancing processes between on-task motivation, achievement, and self-evaluation.


Role of adiponectin and its receptor in prediction of reproductive outcome of metformin treatment in patients with polycystic ovarian syndrome.
The aim of this study was to examine the effect of metformin on serum adiponectin and adiponectin receptor-1 (AdipoR1) and evaluate their role in prediction of ovulation in patients with polycystic ovarian syndrome (PCOS). The study cohort included 68 PCOS patients with clomiphene citrate resistance (group 1) and 28 healthy women as controls (group 2). Baseline serum adiponectin, AdipoR1, total testosterone (T), and homeostasis model of insulin resistance (HOMA-IR) were measured in all participants. Group 1 received metformin (1500 mg/day) for 6 months followed by second blood sampling. Group 1 had significantly lower baseline adiponectin and AdipoR1 (P = 0.001) compared to group 2. During treatment, metformin resulted in conception in 5/68 (7%), ovulation in 33/68 (48%) and regular cycles in 41/68 (60%) patients. Group 1 showed post-metformin higher adiponectin and AdipoR1 (P = 0.01) and lower HOMA-IR (P = 0.006) and T (P = 0.001) compared to pre-treatment levels. Post-metformin ovulatory patients had higher adiponectin and AdipoR1 and lower HOMA-IR and T compared to anovulatory patients. Multivariate regression analysis in group 1 showed that only T and HOMA-IR were significant independent factors for predicting ovulatory cycles during metformin treatment (P = 0.04 and P = 0.05, respectively). Metformin treatment enhances both adiponectin activity and insulin sensitivity, resulting in a less hyperandrogenic state in patients with PCOS. Serum adiponectin and AdipoR1 are poor predictors of ovulatory outcome during treatment.


Markers of Oxidative Stress, Inflammation, and Endothelial Dysfunction in Diabetic and Nondiabetic Patients with Chronic Kidney Disease on Peritoneal Dialysis.
Chronic kidney disease (CKD) is a low-grade inflammatory state which is accom-panied by elevated markers of oxidative stress, inflammatory, and endothelial dysfunction in patients on peritoneal dialysis (PD). These represent a key triad for the development and progression of atherosclerosis. The present study assessed the markers of oxidative stress, inflammatory and endothelial dysfunction in diabetic and non-diabetic CKD patients on PD. A cross-sectional study was undertaken on 100 CKD patients on PD, of whom 52 patients were nondiabetic and 48 were diabetic patients. Blood samples were estimated for malondialdehyde (MDA) and ferric reducing ability of plasma (FRAP) as markers of oxidative stress; interleukin (IL)-6, high-sensitivity C-reactive protein (hs-CRP), and fibrinogen as inflammatory markers; and markers of endothelial dysfunction such as nitric oxide (NO), carotid wall intimal medial thickness (CIMT), and number of plaques, among others. The MDA levels increased and FRAP levels decreased in both diabetic and nondiabetic CKD patients on PD. The levels of IL-6, hs-CRP, fibrinogen, NO, CIMT, and the number of plaques were significantly higher in diabetic patients than in nondiabetic CKD patients on PD. The lipid profile was significantly atherogenic in diabetic patients compared with nondiabetics CKD patients. The results showed increased oxidative stress, inflammation, and endothelial dysfunction in diabetic patients compared with nondiabetics CKD patients on PD.


[Force-dependent effects of interleukin-8 production in endothelial cells exposed to fluid shear stress].
Fluid shear stress plays a key role in many physiological activities and pathological processes of the cardiovascular diseases. In vivo, endothelial cells (ECs) are constantly exposed to hemodynamic force which can modulate structure and function of ECs. Previous studies have demonstrated that IL-8 protein production in endothelial cells was modulated by fluid shear stress, and IL-8 protein production induced by fluid shear stress was time-dependent. In order to identify the role of intensity of fluid shear stress on IL-8 protein production of human umbilical vein endothelial cells (HUVECs), we had HUVECs exposed to shear stress 2.09, 4.61, 6.19, 8.51, 10.50, 12.59, 14.41, 17.22, 18.32 dyne/cm2 respectively and employed quantitative sandwich enzyme-linked immunosorbent assay (ELISA) to measure the IL-8 protein. Here we show that HUVECs untreated with fluid shear stress secreted very little IL-8 in culture media. The IL-8 protein production induced by shear stress was force intensity-dependent. After HUVECs being subjected to low fluid shear stress (2.09 dyne/cm2) for 5 h or 6 h, IL-8 protein production increased and was nearly 6 times or 7 times over that of HUVECs subjected to high fluid shear stress (18.32 dyne/cm2). The linear regression equations between IL-8 protein production (y) and shear stress (dyne/cm2, x) are y=760.12-36.06x, gamma=-0.978 (for 5 h); y=781.87-36.66x, gamma=-0.980 (for 6 h). This in vitro study demonstrates that the production of IL-8 can be regulated by fluid shear stress, and the production of IL-8 induced by shear stress is not only time-dependent but also force intensity-dependent. These observations suggest that the low fluid shear stress induces much more IL-8 secretion, which may play an important role in the pathogenesis and development of both inflammation and atherosclerosis.


Determination of microbial genome sizes by two-dimensional denaturing gradient gel electrophoresis.
In two-dimensional denaturing gradient gel electrophoresis, DNA is digested with a restriction endonuclease and the resulting DNA fragments are separated as a function of size by conventional agarose gel electrophoresis. Following this first dimension electrophoresis, the fragment distribution is placed at the top of a denaturing gradient slab gel and electrophoresis is carried out parallel to the gradient direction. This second dimension separation is a complex function of the base sequence of each fragment. Analysis of the DNA fragment distribution as a function of fragment size allows the DNA size to be calculated. This method has been applied to calculate three microbial genome sizes: Mycoplasma capricolum, 724 kb; Acholeplasma laidlawii, 1646 kb; and Hemophilus influenzae, 1833 kb.


Filamin A is a novel caveolin-1-dependent target in IGF-I-stimulated cancer cell migration.
Caveolin-1 is an essential structural constituent of caveolae which is involved in regulation of mitogenic signaling and oncogenesis. Caveolin-1 has been implicated in cell migration but its exact role and mechanism of action in this process remained obscure. We have previously reported that expression of caveolin-1 in stably transfected MCF-7 human breast cancer (MCF-7/Cav1) cells up-regulates phosphorylation of a putative Akt substrate protein, designated pp340 [D. Ravid, S. Maor, H. Werner, M. Liscovitch, Caveolin-1 inhibits cell detachment-induced p53 activation and anoikis by upregulation of insulin-like growth factor-I receptors and signaling, Oncogene 24 (2005) 1338-1347.]. We now show, using differential detergent extraction, SDS-PAGE and mass spectrometry, that the major protein in the pp340 band is the actin filament cross-linking protein filamin A. The identity of pp340 as filamin A was confirmed by immunoprecipitation of pp340 with specific filamin A antibodies. RT-PCR, flow cytometry and Western blot analyses show that filamin A mRNA and protein levels are respectively 3.5- and 2.5-fold higher in MCF-7/Cav1 cells than in MCF-7 cells. Basal filamin A phosphorylation on Ser-2152, normalized to total filamin A levels, is 7.8-fold higher in MCF-7/Cav1 than in MCF-7 cells. Insulin-like growth factor-I (IGF-I) stimulates phosphorylation of filamin A on Ser-2152 in MCF-7 cells and further enhances Ser-2152 phosphorylation over its already high basal level in MCF-7/Cav1 cells. The effect of IGF-I is inhibited by the PI3K inhibitor wortmannin, indicating that IGF-I-stimulated phosphorylation of filamin A occurs via the PI3K/Akt pathway. Co-immunoprecipitation experiments have confirmed a previous report showing that filamin A and caveolin-1 co-exist in a complex and have revealed the presence of active phospho-Akt in this complex. Ser-2152 phosphorylation of filamin A has been implicated in cancer cell migration. Accordingly, caveolin-1 expression dramatically enhances IGF-I-dependent MCF-7 cell migration. These data indicate that caveolin-1 specifies filamin A as a novel target for Akt-mediated filamin A Ser-2152 phosphorylation thus mediating the effects of caveolin-1 on IGF-I-induced cancer cell migration.


Heat shock locus 93D of Drosophila melanogaster: a spliced RNA most strongly conserved in the intron sequence.
The Drosophila melanogaster heat shock locus at 93D encodes at least three overlapping transcripts, 10-12 kilobases (kb), 1.9 kb, and 1.2 kb. The abundance of the three transcripts is significantly increased during heat shock; however, all are also found in non-heat-shocked cells. The 1.2-kb transcript is found in the cytoplasm. Sequence analysis of a 1.1-kb cDNA clone representing sequences within the 1.2-kb transcript and comparison to genomic sequences indicate that it is spliced; 700 base pairs of sequence found in genomic DNA are removed from the middle of the transcript. Sequence analysis further suggests that this RNA does not encode a heat shock protein. The largest open reading frame beginning with a methionine codon would encode a polypeptide of 34 amino acids. We have not been able to detect a heat shock-induced polypeptide of this size. A DNA clone from the analogous heat shock puff of Drosophila hydei has been analyzed by hybridization with the small subclones used to sequence the D. melanogaster cDNA plus a genomic fragment containing the 700-base-pair intron. Results of this hybridization indicated strong homology of the intron fragment. Weaker homology was detected with the two small fragments flanking the intron. Other fragments of the D. melanogaster cDNA showed no hybridization to the cloned D. hydei puff DNA.


Short-term results under three different immunosuppressive regimens at one center.
We examined short-term outcomes and posttransplant medical complications under three different immunosuppressive regimens at a single center. The study design was a randomized, prospective, open-label trial comparing a calcineurin inhibitor-free (CNI) protocol to standard triple therapy with tacrolimus, prednisone, and mycophenolate mofetil. They were also compared to a concurrent but nonrandomized third cohort treated with a prednisone-free protocol. All three groups had excellent early outcomes with no significant difference in patient or graft survival or biopsy-proven acute rejection. Serum creatinine was significantly lower in the CNI-free recipients. Lipid panels and posttransplant diabetes mellitus were significantly lower in the prednisone-free patients. Prednisone-free kidney transplant recipients have improved early glucose metabolism and hyperlipidemia compared to CNI-free or standard triple therapy recipients with comparable rejection and graft survival rates.


The effect of lead-contaminated soil from Canadian prairie skeet ranges on the neutral red retention assay and fecundity in the earthworm Eisenia fetida.
The sublethal effects of lead (Pb) on the earthworm Eisenia fetida were evaluated in the laboratory using freshly spiked soil and soil collected from Canadian prairie skeet ranges. After a four-week exposure to soil spiked with lead acetate, earthworm neutral red retention time (NRRT). soil Pb concentrations, and earthworm Pb body burdens were measured. Lysosomal NRRT was reduced in a concentration-dependent manner (p < 0.0001), and NRRT was negatively correlated with earthworm Pb body burdens (r = -0.80, p < 0.0001). To evaluate the effects of aged Pb, earthworms were exposed to soil from three skeet ranges, and responses were compared with three matched reference sites. After a four-week exposure, NRRT, growth, fecundity, soil total Pb levels, and earthworm Pb body burdens were measured. The potentially bioavailable fraction of Pb in these sites was measured using a Ca(NO3)2 extraction. Growth and fecundity did not differ significantly between any of the skeet ranges and their reference sites. However, NRRT was significantly reduced in all three ranges compared with their respective reference sites (p < 0.05), indicating that the neutral red retention assay (NRRA) may be useful for detecting toxicity and potential hazards at Pb-contaminated sites. Lysosomal NRRT was negatively correlated with soil Ca(NO3)2-extractable Pb (r = -0.80, p < 0.0001) and soil total Pb (r = -0.73, p = 0.001). Lysosomal NRRT was negatively correlated (r = -0.67, p < 0.002) with earthworm Pb tissue levels.


Photoluminescence of gamma-irradiated Beryllium oxide.
This study analyses the emission and excitation spectra of Beryllium Oxide (BeO) unirradiated and irradiated with 60Co gamma radiation because of its potential use in radiation dosimetry. Deconvolution of the spectra showed that using an excitation wavelength λexc = 330 nm, four emission bands centered at 404, 430, 468 and 545 nm are obtained; These emission bands appear in both irradiated and non-irradiated BeO; however, the irradiated samples exhibited an extra emission band centered at 416 nm. The excitation spectrum was obtained by setting the emission monochromator at a wavelength λ0 = 400 nm. By means of deconvolution, it was obtained that the emission spectrum of the non-irradiated samples is constituted by two bands centered at 307 and 331 nm, while for the irradiated samples the spectrum has three components centered at 297, 334 and 317 nm. In addition, it was found that the area under the curve of all emission bands decreases after irradiation, this may be due to the formation of electron-hole pairs after irradiation, which have the effect of reducing radiative phenomena, which it could be favorable for the applications of BeO in ionizing radiation dosimetry.


Pueraria lobata Targeted Preparation Improves the Clinical Symptoms of Cervical Spondylosis by Regulating the Balance of Gut Microbiota.
Nanotargeted preparations can enhance the safety and effectiveness of medication by altering the pharmacokinetic behavior of drugs in the human body, and Pueraria lobata is shown to be effective in the treatment of neck and back pain. This study prepared a nano-Pueraria targeted preparation, in order to analyze its effect on improving the clinical symptoms of cervical spondylosis by adjusting the balance of intestinal flora. A total of 200 patients with cervical spondylosis admitted to the Affiliated Hospital of Nanjing University of Chinese Medicine were enrolled and divided into an observation group and a control group. The control group was given Tuina therapy, and the observation group was given nano-Pueraria targeted preparation + Tuina therapy. The clinical symptoms and intestinal microflora of the two groups were examined before intervention. It was found that the markedly effective of treatment efficacy of the observation group (98%) was higher than that of the control group (78%) after 15 days of intervention, and the clinical symptoms were obviously fewer than those of the control group. The distribution of gut microbiota showed that there were significant differences in the composition of gut microbiota between the two groups. Compared with the control group, the abundance of Firmicutes in the observation group was significantly higher, while the abundance of Bacteroidetes and Proteobacteria was significantly lower. The targeted preparation of nano-Pueraria can improve the clinical symptoms of patients with cervical spondylosis by adjusting the balance of gut microbiota.


Endometriosis, Oocyte, and Embryo Quality.
Endometriosis is a common finding among women with infertility, and women who are diagnosed with endometriosis are almost twice as likely to experience infertility. Mechanisms by which endometriosis causes infertility remain poorly understood. In this review, we evaluate the current literature on the impact of endometriosis on oocyte and embryo quality. The presence of endometriosis evidently reduces ovarian reserve, oocyte quality, and embryo quality; however, this does not appear to translate to a clear clinical impact. Analysis of data from large assisted reproduction technology registries has shown that women with endometriosis have a lower oocyte yield but no reduction in reproductive outcomes. There is a need for future studies in the form of well-designed randomized controlled trials to further evaluate the role of surgical and medical treatment options in women with endometriosis undergoing assisted conception.


The Pharmaceutical Industry in 2016. An Analysis of FDA Drug Approvals from a Perspective of the Molecule Type.
This is an analysis from a chemical point of view of the 22 drugs accepted by the FDA during 2016. The different drugs from the 2016 "harvest" have been classified according to their chemical structure: antibodies; TIDES (oligonucleotides and peptides); amino acids and natural products; drug combination; and small molecules.


Endoscopic Coregistered Ultrasound Imaging and Precision Histotripsy: Initial In Vivo Evaluation.
Objective. Initial performance evaluation of a system for simultaneous high-resolution ultrasound imaging and focused mechanical submillimeter histotripsy ablation in rat brains. Impact Statement. This study used a novel combination of high-resolution imaging and histotripsy in an endoscopic form. This would provide neurosurgeons with unprecedented accuracy in targeting and executing nonthermal ablations in minimally invasive surgeries. Introduction. Histotripsy is a safe and effective nonthermal focused ablation technique. However, neurosurgical applications, such as brain tumor ablation, are difficult due to the presence of the skull. Current devices are too large to use in the minimally invasive approaches surgeons prefer. We have developed a combined imaging and histotripsy endoscope to provide neurosurgeons with a new tool for this application. Methods. The histotripsy component had a 10 mm diameter, operating at 6.3 MHz. Affixed within a cutout hole in its center was a 30 MHz ultrasound imaging array. This coregistered pair was used to ablate brain tissue of anesthetized rats while imaging. Histological sections were examined, and qualitative descriptions of ablations and basic shape descriptive statistics were generated. Results. Complete ablations with submillimeter area were produced in seconds, including with a moving device. Ablation progress could be monitored in real time using power Doppler imaging, and B-mode was effective for monitoring post-ablation bleeding. Collateral damage was minimal, with a 100 μm maximum distance of cellular damage from the ablation margin. Conclusion. The results demonstrate a promising hardware suite to enable precision ablations in endoscopic procedures or fundamental preclinical research in histotripsy, neuroscience, and cancer.


Immunoassay by particle counting for coagulation testing: application to the determination of antithrombin III, von Willebrand factor antigen (vWF:Ag) and plasminogen.
Based on immunoassay by particle counting, three methods for antithrombin III, von Willebrand factor and plasminogen were developed on an automated IMPACT machine and on a semi-automated MULTIPACT system. Precision of the techniques, measured at low, medium and high level of the calibration curve showed coefficients of variation varying from 4.3 to 13.8%. Accuracy was evaluated by dilution recovery test and by correlation with rocket immunoelectrophoresis and chromogenic substrate techniques. The results show that the proposed methods correlate well with existing techniques and that immunoassay by particle counting is applicable to several coagulation tests.


Effect of baicalin on oxygen-glucose deprivation-induced endothelial cell damage.
Baicalin, a plant-derived flavonoid, has been reported to exert neuroprotective effects on ischemia-like or excitotoxic injury. To confirm this function and explore the possible mechanism, we investigated the protective effect of baicalin on an in-vitro model of ischemia (oxygen-glucose deprivation-treated endothelial cell). In the present study, we found that baicalin (100 μM) inhibited cell death, reduced cell membrane damage, and maintained the integrity of the nucleus. Flow cytometric analysis and Hoechst 33258/propidium iodide double staining results showed that the necroptosis ratio decreased with baicalin treatment. Western blot analysis showed that baicalin regulated the expression of RIP-1 and RIP-3 in bEnd.3 cells and the use of detection kits showed that baicalin inhibited the production of reactive oxygen species and malondialdehyde, and increased the activity of superoxide dismutase in oxygen-glucose deprivation-treated bEnd.3 cells. These results indicated that baicalin effectively alleviated the oxidative stress, decreased the proportion of cells undergoing necrosis, and reduced cell damage.


The effect of an acute fast on human head and neck carcinoma xenograft. Growth effects on an 'isolated tumor vascular pedicle' in the nude rat.
The effects of nutritional state on tumor growth are poorly understood. Most animal studies to date suggest an inhibitory effect of nutritional depletion on tumor growth and a stimulatory effect of nutritional repletion or overfeeding. We have modified an "isolated tumor vascular pedicle" model in the nude rat to study the growth and tumor-specific nutrient utilization of the FaDu cell line of human hypopharyngeal squamous carcinoma. Two weeks after tumor implantation, rats were randomized to either a fed or fasted study group for an additional 7 days. Tumors were significantly larger in the fasted group (0.602 +/- 0.215 g vs 0.362 +/- 0.104 g; P < .02). Whole blood nutrient gradients were determined across the tumor and systemic tissues in both groups. The nutrient gradients across these tissues were significantly different in the fed animals and approached statistical significance in the fasted animals. In addition, there appeared to be a greater utilization of glucose in the fed group (-0.401 +/- 0.904 mmol/L vs -0.298 +/- 0.589 mmol/L), while there was a greater production of lactate in the fasted group (0.798 +/- 0.518 mmol/L vs 0.046 +/- 0.639 mmol/L; P < .1). Flow cytometric analysis revealed no difference in the percentage of cells in any particular stage of the cell cycle between the two groups. These results suggest that the maintenance of adequate body weight may be beneficial not only to the nutrition of the cachectic tumor-bearing host but may also prevent a ketotic state or state of lipolysis that may be preferential to the tumor.


Dynamic contrast change produces rapid gain control in visual cortex.
During normal vision, objects moving in the environment, our own body movements and our eye movements ensure that the receptive fields of visual neurons are being presented with continually changing contrasts. Thus, the visual input during normal behaviour differs from the type of stimuli traditionally used to study contrast coding, which are presented in a step-like manner with abrupt changes in contrast followed by prolonged exposure to a constant stimulus. The abrupt changes in contrast typically elicit brief periods of intense firing with low variability called onset transients. Onset transients provide the visual system with a powerful and reliable cue that the visual input has changed. In this paper we investigate visual processing in the primary visual cortex of cats in response to stimuli that change contrast dynamically. We show that 1-4 s presentations of dynamic increases and decreases in contrast can generate stronger contrast gain control than several minutes exposure to a stimulus of constant contrast. Thus, transient mechanisms of contrast coding are not only less variable than sustained responses but are also more rapid and flexible. Finally, we propose a quantitative model of contrast coding which accounts for changes in spike rate over time in response to dynamically changing image contrast.


A novel transdermal delivery system for the anti-inflammatory lumiracoxib: influence of oleic acid on in vitro percutaneous absorption and in vivo potential cutaneous irritation.
Transdermal delivery of non-steroidal anti-inflammatory drugs may be an interesting strategy for delivering these drugs to the diseased site, but it would be ineffective due to low skin permeability. We investigated whether oleic acid (OA), a lipid penetration enhancer in poloxamer gels named poloxamer-based delivery systems (PBDS), can improve lumiracoxib (LM) delivery to/through the skin. The LM partition coefficient (K) studies were carried out in order to evaluate the drug lipophilicity grade (K(octanol/buffer)), showing values >1 which demonstrated its high lipophilicity. Both in vitro percutaneous absorption and skin retention studies of LM were measured in the presence or absence of OA (in different concentrations) in PBDS using porcine ear skin. The flux of in vitro percutaneous absorption and in vitro retention of LM in viable epidermis increased in the presence of 10.0% (w/w) OA in 25.0% (w/w) poloxamer gel. In vivo cutaneous irritation potential was carried out in rabbits showing that this formulation did not provide primary or cumulative cutaneous irritability in animal model. The results showed that 25.0% poloxamer gel containing 10.0% OA is potential transdermal delivery system for LM.


The role of rare innate immune cells in Type 2 immune activation against parasitic helminths.
The complexity of helminth macroparasites is reflected in the intricate network of host cell types that participate in the Type 2 immune response needed to battle these organisms. In this context, adaptive T helper 2 cells and the Type 2 cytokines interleukin (IL)-4, IL-5, IL-9 and IL-13 have been the focus of research for years, but recent work has demonstrated that the innate immune system plays an essential role. Some innate immune cells that promote Type 2 immunity are relatively abundant, such as macrophages and eosinophils. However, we now appreciate that more rare cell types including group 2 innate lymphoid cells, basophils, mast cells and dendritic cells make significant contributions to these responses. These cells are found at low frequency but they are specialized to their roles - located at sites such as the skin, lung and gut, where the host combats helminth parasites. These cells respond rapidly and robustly to worm antigens and worm-induced damage to produce essential cytokines, chemokines, eicosanoids and histamine to activate damaged epithelium and to recruit other effectors. Thus, a greater understanding of how these cells operate is essential to understand how the host protects itself during helminth infection.


[PCDH19 gene mutations lead to epilepsy with mental retardation limited to females in 2 cases and literature review].
Epilepsy with mental retardation limited to females (EFMR) is a syndrome characterized by early onset heat-sensitive epilepsy of infancy or early childhood and generally limited to females, which previously reported that the cadherin gene superfamily subtype protocadherin 19 (PCDH19) gene is its pathogenic gene. We retrospectively analyzed the clinical data for 2 cases of EFMR patients with PCDH19 mutation diagnosed by Department of Pediatric Neurology of Xiangya Hospital, Central South University in 2015. Literature on PubMed, OMIM and HGMD relevant to this syndrome was reviewed, and the clinical characteristics were summarized accordingly. The 2 cases are consistent with the typical clinical manifestations of EFMR caused by PCDH19 mutations. Their seizures are heat sensitive, with or without screaming, and expressed in various forms. Cognitive impairment or autism-like performance were often identified in these patients, hematuria metabolic diseases screening was normal, no abnormal MRI imaging of the head, and de novo PCDH19 gene mutations were found in their epilepsy gene chip sequencing. It is noteworthy that this disease is very similar to the clinical manifestations of the Dravet syndrome due to the mutations of the neurotype sodium channel α1 subunit SCN1A. Therefore, in female patients whose clinical manifestations resemble to Dravet syndrome but SCN1A gene test were negative, EFMR with PCDH19 mutation should be taken into consideration. Early PCDH19 gene testingis of great significance because it not only helps clinicians to understand and analyze the prognosis of this disease, but also offers genetic counseling to the parents.


Metastable state en route to traveling-wave synchronization state.
The Kuramoto model with mixed signs of couplings is known to produce a traveling-wave synchronized state. Here, we consider an abrupt synchronization transition from the incoherent state to the traveling-wave state through a long-lasting metastable state with large fluctuations. Our explanation of the metastability is that the dynamic flow remains within a limited region of phase space and circulates through a few active states bounded by saddle and stable fixed points. This complex flow generates a long-lasting critical behavior, a signature of a hybrid phase transition. We show that the long-lasting period can be controlled by varying the density of inhibitory/excitatory interactions. We discuss a potential application of this transition behavior to the recovery process of human consciousness.


Interlamellar refractive keratoplasty in rabbits.
The suitability and effectiveness of hydrophilic soft contact lenses and donor corneal buttons for interlamellar refractive keratoplasty were evaluated in a study with rabbits. In each experimental eye a trephined button of Bausch & Lomb Soflens (polymacon), Cooper Permalens (perfilcon A) or rabbit cornea 6.5 mm in diameter was inserted in a corneal pocket created with a lamellar dissector. Among the inserts available for long-term follow-up all five of the Soflens inserts showed "melting" (perforation and sloughing) by 3 weeks, whereas six of the seven Permalens inserts and all four of the donor corneal inserts were clear at 3 to 6 months. Myopia was induced and the corneal curvature steepened with all but the high-minus Soflens inserts. Thus, interlamellar refractive keratoplasty with soft contact lenses of high water content or lathe-cut donor corneal buttons has potential for the correction of aphakia in rabbits and may well have similar potential in humans.


Penicillin-binding proteins as resistance determinants in clinical isolates of Streptococcus pneumoniae.
Altered penicillin-binding proteins (PBPs) with reduced affinity for penicillin are encoded by mosaic genes in penicillin-resistant clinical isolates of Streptococcus pneumoniae. Generally, members of one bacterial clone contain the same mosaic gene. We report here on a serotype 19A clone of penicillin- and multiple-resistant S. pneumoniae prevalent in Hungary, members of which are exceptionally diverse in terms of PBP properties. The pbp2x gene of four 19A isolates was sequenced, and a distinct mosaic structure detected in each case. The pbp2x genes also differed from a homologous gene of a high-level penicillin-resistant S. mitis from Hungary. The contribution of PBPs to resistance development was studied on transformation experiments using the laboratory strain R6 as recipient, and PBP genes from the type 19A isolate Hu11. pbp2x and pbp2b function as primary resistance determinants for different beta-lactams. Secondary transformation with pbp1a increased the resistance level considerably for penicillins and cefotaxime. Chromosomal DNA of a high-level penicillin- and cefotaxime-resistant S. mitis from Hungary also transformed the R6 strain to increased resistance levels, and PBP2x and PBP2b functioned as primary resistance determinants as above. In contrast, high-level cefotaxime resistance appeared to be due to a low affinity PBP2a, indicating that this PBP can also function as a resistance determinant.


A Rasch analysis of the pain catastrophizing scale supports its use as an interval-level measure.
To evaluate the properties of the Pain Catastrophizing Scale (PCS) from a Rasch paradigm. A secondary analysis of 235 patients with work-related pain conditions was performed using the Rasch methodology. Unidimensionality, item fit, location independence, differential item functioning, response option structure, and linearity were evaluated for the 13-item PCS score. Two items (8 and 12) required rescoring to address disordered response thresholds. Significant misfit to the Rasch model was corrected through the use of testlets based on the original 3 factors of the PCS (rumination, magnification, and helplessness). After rescoring and creation of testlets, the scale showed good fit to the Rasch model (χ(2)=6.93, P=0.91) and could be logically considered an interval-level scale. No evidence of differential item functioning was found for sex or location of pain. The items in the scale covered the spectrum of catastrophizing levels reported by the sample. A transformation matrix is presented that allows simple conversion of ordinal to interval-level scores. The results of this secondary analysis suggest that the PCS can be appropriately evaluated as an interval-level scale when the composite 13-item score is considered, as has been standard practice to date. Implications for clinical and research use are discussed.


Investigating the Health and Health-Related Quality of Life Impacts of the Criminal Legal System on Families: A Scoping Review.
A scoping review was conducted to present the state of the science regarding the health and health-related quality of life (HRQOL) effects of having a family member in contact with the criminal legal system (CLS). The review examined how the following have been studied: 1) types of family relationships, 2) the point of CLS contact, 3) mental health outcomes, 4) physical health outcomes, and 5) HRQOL outcomes. The final sample of 40 studies was largely secondary analyses of datasets (93%; n=37) that investigated a parent-child relationship (78%; n=31). Incarceration was the most frequently measured point of CLS contact (85%; n=34). Mental health outcomes were measured in 68% of the studies (n=27). Physical health outcomes were measured in 28% of the studies (n=11). Health-related quality of life outcomes were included in half of the studies (50%; n=20). Study findings indicate exposure to the CLS through a family member is associated with poorer health and HRQOL outcomes.


9-Lipoxygenase-Derived Oxylipins Activate Brassinosteroid Signaling to Promote Cell Wall-Based Defense and Limit Pathogen Infection.
The oxylipins, a large family of oxygenated lipid derivatives, regulate plant development and immunity. Two members of the 9-lipoxygenase (9-LOX) oxylipin pathway, 9-hydroxyoctadecatrienoic acid and 9-ketooctadecatrienoic acid, control root development and plant defense. Studies in Arabidopsis (Arabidopsis thaliana) using a series of 9-hydroxyoctadecatrienoic acid- and 9-ketooctadecatrienoic acid-insensitive nonresponding to oxylipins (noxy) mutants showed the importance of the cell wall as a 9-LOX-induced defense component and the participation of NOXY proteins in signaling cell wall damage. Here, we examined 9-LOX signaling using the mutants lox1lox5, which lacks 9-LOX activity, and noxy2-2, which shows oxylipin insensitivity and mitochondrial dysfunction. Mutants in brassinosteroids (BRs), a class of plant hormones necessary for normal plant growth and the control of cell wall integrity, were also analyzed. Several lines of evidence indicated that 9-LOX-derived oxylipins induce BR synthesis and signaling to activate cell wall-based responses such as callose deposition and that constitutive activation of BR signaling in bri1-EMS-suppressor 1-D (bes1-D) plants enhances this response. We found that constitutive BR signaling in bes1-D and brassinolide-resistant 1-1D (bzr1-1D) mutants conferred resistance to Pseudomonas syringae. bes1-D and bzr1-1D showed increased resistance to Golovinomyces cichoracearum, an obligate biotrophic fungus that penetrates the cell wall for successful infection, whereas susceptibility was enhanced in lox1lox5 and noxy2-2. Our results indicate a sequential action of 9-LOX and BR signaling in activating cell wall-based defense, and this response prevents pathogen infection. These results show interaction between the 9-LOX and BR pathways and help to clarify their role in modulating plant defense.


Expression of multiple species of basic fibroblast growth factor mRNA and protein in normal and tumor-derived mammary epithelial cells in culture.
We examined the expression of the basic fibroblast growth factor (bFGF) gene in cultured normal and tumor-derived human mammary epithelial cells at both the transcriptional and translational level. Northern blot analysis revealed three bFGF mRNA transcripts of 7.5, 4.4, and 2.2 kilobases in all four strains (donors) of normal cells (HMECs) we examined and in the immortal mammary cell line HBL-100. Of the four mammary tumor-derived cell lines we examined (MCF-7, BT-474, T-47D, and Hs578T), only the Hs578T cells produced detectable levels of bFGF mRNA. Western blot analysis of cell lysates using an anti-bFGF monoclonal antibody revealed corresponding results. bFGF protein was detected in normal HMEC strains 161 and 48 (other normal strains not tested), in HBL-100 cells, and in Hs578T cells, but not in the other tumor cell lines. In each case, three distinct molecular weight species of bFGF protein were detected which migrated in sodium dodecyl sulfate-polyacrylamide gel at 18, 24, and 27 kDa. We also investigated the ability of bFGF to stimulate the proliferation of normal and tumor-derived mammary epithelial cells. Addition of bFGF to serum-free cultures of these cells had no effect on the proliferation of HMECs under a variety of conditions and was weakly mitogenic for Hs578T cells. Our results indicate that normal HMECs produce bFGF mRNA and protein(s), whereas only some mammary tumor-derived cells express this gene. Thus, our results do not support a general role for expression/overexpression of bFGF in the development of mammary tumors. However, bFGF could play a role in the normal development and homeostasis of the mammary gland.


Validation of rapid 4-component body composition assessment with the use of dual-energy X-ray absorptiometry and bioelectrical impedance analysis.
The 4-component (4C) model is a criterion method for human body composition that separates the body into fat, water, mineral, and protein, but requires 4 measurements with significant cost and time requirements that preclude wide clinical use. A simplified model integrating only 2 measurements-dual-energy X-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA)-and 10 min of patient time has been proposed. We aimed to validate a rapid, simplified 4C DXA + BIA body composition model in a clinical population. This was a cross-sectional observational study of 31 healthy adults. Participants underwent whole-body DXA, segmental BIA, air displacement plethysmography (ADP), and total body water (TBW) measurement by deuterium (D2O) dilution. 4C composition was calculated through the use of the Lohman model [DXA mineral mass, D2O TBW, ADP body volume (BV), scale weight] and the simplified model (DXA mineral mass and BV, BIA TBW, scale weight). Accuracy of percentage of fat (%Fat) and protein measurements was assessed via linear regression. Test-retest precision was calculated with the use of duplicate DXA and BIA measurements. Of 31 participants, 23 were included in the analysis. TBWBIA showed good test-retest precision (%CV = 5.2 raw; 1.1 after outlier removal) and high accuracy to TBWD2O [TBWD2O = 0.956*TBWBIA, R2= 0.92, root mean squared error (RMSE) = 2.2 kg]. %Fat estimates from DXA, ADP, D2O, and BIA all showed high correlation with the Lohman model. However, only the 4C simplified model provides high accuracy for both %Fat (R2 = 0.96, RMSE = 2.33) and protein mass (R2= 0.76, RMSE = 1.8 kg). %Fat precision from 4C DXA + BIA was comparable with DXA (root mean square-SD = 0.8 and 0.6 percentage units, respectively). This work validates a simplified 4C method that measures fat, water, mineral, and protein in a 10-min clinic visit. This model has broad clinical application to monitor many conditions including over/dehydration, malnutrition, obesity, sarcopenia, and cachexia.


Unexpected Hydrated Electron Source for Preparative Visible-Light Driven Photoredox Catalysis.
The hydrated electron is experiencing a renaissance as a superreductant in lab-scale reductions driven by light, both for the degradation of recalcitrant pollutants and for challenging chemical reactions. However, examples for its sustainable generation under mild conditions are scarce. By combining a water-soluble Ir catalyst with unique photochemical properties and an inexpensive diode laser as light source, we produce hydrated electrons through a two-photon mechanism previously thought to be unimportant for laboratory applications. Adding cheap sacrificial donors turns our new hydrated electron source into a catalytic cycle operating in pure water over a wide pH range. Not only is that catalytic system capable of detoxifying a chlorinated model compound with turnover numbers of up to 200, but it can also be employed for two novel hydrated electron reactions, namely, the decomposition of quaternary ammonium compounds and the conversion of trifluoromethyl to difluoromethyl groups.


Isolated microvessels: the blood-brain barrier in vitro.
Isolated bovine retinal and brain microvessels, exhibiting a patent lumen, were used to study the contribution of the microvasculature to the blood-brain and blood-retina barriers. The diffusion marker, sucrose, was taken up slowly by the isolated microvessels in contrast to leucine, tyrosine, and valine which were taken up at a considerably faster rate. Uptake of leucine was temperature dependent but resistant to inhibition by ouabain and sodium azide. The large neutral amino acids exhibited stereospecificity and cross-competition for uptake by the isolated microvessels. The apparent Kms for uptake for tyrosine, leucine, and valine were III micron,133 micron, and 500 micron, respectively.


The footprint of genome architecture in the largest genome expansion in RNA viruses.
The small size of RNA virus genomes (2-to-32 kb) has been attributed to high mutation rates during replication, which is thought to lack proof-reading. This paradigm is being revisited owing to the discovery of a 3'-to-5' exoribonuclease (ExoN) in nidoviruses, a monophyletic group of positive-stranded RNA viruses with a conserved genome architecture. ExoN, a homolog of canonical DNA proof-reading enzymes, is exclusively encoded by nidoviruses with genomes larger than 20 kb. All other known non-segmented RNA viruses have smaller genomes. Here we use evolutionary analyses to show that the two- to three-fold expansion of the nidovirus genome was accompanied by a large number of replacements in conserved proteins at a scale comparable to that in the Tree of Life. To unravel common evolutionary patterns in such genetically diverse viruses, we established the relation between genomic regions in nidoviruses in a sequence alignment-free manner. We exploited the conservation of the genome architecture to partition each genome into five non-overlapping regions: 5' untranslated region (UTR), open reading frame (ORF) 1a, ORF1b, 3'ORFs (encompassing the 3'-proximal ORFs), and 3' UTR. Each region was analyzed for its contribution to genome size change under different models. The non-linear model statistically outperformed the linear one and captured >92% of data variation. Accordingly, nidovirus genomes were concluded to have reached different points on an expansion trajectory dominated by consecutive increases of ORF1b, ORF1a, and 3'ORFs. Our findings indicate a unidirectional hierarchical relation between these genome regions, which are distinguished by their expression mechanism. In contrast, these regions cooperate bi-directionally on a functional level in the virus life cycle, in which they predominantly control genome replication, genome expression, and virus dissemination, respectively. Collectively, our findings suggest that genome architecture and the associated region-specific division of labor leave a footprint on genome expansion and may limit RNA genome size.


Pretreatment of bamboo residues with Coriolus versicolor for enzymatic hydrolysis.
Pretreatment by a white-rot fungus Coriolus versicolor B1 under different conditions and saccharification of bamboo were investigated. The saccharification rate was significantly enhanced and a maximum saccharification rate of 37.0% was achieved after pretreatment. Reducing sugars yield was 223.2 mg/g of bamboo residues, which was 2.34 times that of the raw material. It was feasible to treat bamboo residues with B1 for the saccharification of bamboo.


Time-delay concealment and complexity enhancement of an external-cavity laser through optical injection.
The concealment of the time-delay signature (TDS) of chaotic external-cavity lasers is necessary to ensure the security of optical chaos-based cryptosystems. We show that this signature can be removed simply by optically injecting an external-cavity laser with a large linewidth-enhancement factor into a second, noninjection-locked, semiconductor laser. Concealment is ensured both in the amplitude and in the phase of the optical field, satisfying a sought-after property of optical chaos-based communications. Meanwhile, enhancement of the dynamical complexity, characterized by permutation entropy, coincides with strong TDS suppression over a wide range of parameters, the area for which depends sensitively on the linewidth-enhancement factor.


On the binding of tRNA to Escherichia coli RNA polymerase. Interactions between the core enzyme, DNA and tRNA.
We have investigated the interplay between the binding of tRNA and DNA to core RNA polymerase. We show that the monomer core enzyme can bind stably to either DNA or tRNA, whereas the dimer core can fix both DNA and tRNA in a stable ternary complex. We have examined the kinetics of the exchange between DNA and tRNA bound to the core enzyme. DNA bound to monomer core can be rapidly displaced by tRNA without prior dissociation of the core from the DNA. Similarly tRNA bound to the core can be displaced by DNA without prior dissociation of the tRNA. We confirm the result of Hinkle and Chamberlin [J. Mol. Biol. 70, 157-185 (1972)] that, in contrast, the core enzyme must first dissociate from one DNA molecule before it can transfer to another DNA. As this dissociation is very slow we suggest that, in vivo, the tRNA can act as a 'porter' providing the core enzyme with a more kinetically favourable path to transfer from one DNA site to another.


QUEST+: A general multidimensional Bayesian adaptive psychometric method.
QUEST+ is a Bayesian adaptive psychometric testing method that allows an arbitrary number of stimulus dimensions, psychometric function parameters, and trial outcomes. It is a generalization and extension of the original QUEST procedure and incorporates many subsequent developments in the area of parametric adaptive testing. With a single procedure, it is possible to implement a wide variety of experimental designs, including conventional threshold measurement; measurement of psychometric function parameters, such as slope and lapse; estimation of the contrast sensitivity function; measurement of increment threshold functions; measurement of noise-masking functions; Thurstone scale estimation using pair comparisons; and categorical ratings on linear and circular stimulus dimensions. QUEST+ provides a general method to accelerate data collection in many areas of cognitive and perceptual science.


Homocysteine and Digestive Tract Cancer Risk: A Dose-Response Meta-Analysis.
Homocysteine, a key component in one-carbon metabolism, is of great importance in remethylation. Many epidemiologic studies have assessed the association between homocysteine and risk of digestive tract cancer, but the results are inconsistent. The objective of our meta-analysis is to assess the association between homocysteine and digestive tract cancer risk. Comprehensive searches were performed on the PubMed, Embase, Cochrane, and Web of Science databases up to September 25, 2018, to identify relevant studies. Thirteen studies were included in the meta-analysis. Odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were used to estimate the strength of the relationship between homocysteine and the risk of digestive tract cancer. The pooled OR of digestive tract cancer risk for patients with the highest categories of blood homocysteine levels versus the lowest categories was 1.27 (95% CI, 1.15, 1.39) with no significant heterogeneity observed (P = 0.798, I 2 = 0.0%). Moreover, the dose-response analysis revealed that each 5μmol/L increase in homocysteine increased the incidence of digestive tract cancer by 7%. Generally, our results indicated that elevated homocysteine was associated with higher risk of digestive tract cancer. That is, homocysteine concentration may be a potential biomarker for occurrence of digestive tract cancer.


[Tuberculosis control in the Central Health Region of Catalonia during the period 1986-2000].
To assess tuberculosis control in the Central Health Region, Catalonia, Spain, from the implementation of the area's Tuberculosis Control Program in 1986 until the year 2000. To study the epidemiological profile of tuberculosis and the outcome of the following control measures in sputum smear-positive patients: final outcome of treatment and monitoring, and the percentage of patients for whom a contact investigation (CI) was carried out. Tuberculosis control is considered effective if the sum of noncompliant patients, plus the cases in which treatment failed, plus the patients transferred out remains below 10% of the cohort of patients studied, and if a CI has been conducted in at least 80% of this cohort. The number of cases reported was 6326, of which 7% were retreatments. A total of 5865 new cases was detected. Of these, 5652 (96%) were patients born in Spain. The number of cases reported annually peaked in 1990 (474) and then declined continuously until 2000, when it was 54% lower (220). Foreign-born patients numbered 213 (4%), and 95% of them came from countries with a high prevalence of tuberculosis. In the cohort of patients studied between 1997 and 2000, the sum of noncompliant patients, plus cases in which treatment failed, plus the patients transferred out came to 11%. Since 1994, a CI has been carried out for over 80% of patients, and this figure reached 92% in 2000. We consider that a substantial degree of tuberculosis control has been achieved given the decline in tuberculosis morbidity among people born in Spain, the fact that the percentage of noncompliant patients, treatment failures and transfers was only slightly over 10%, and that a CI has been conducted for over 80% of patients since 1994 (92% in 2000).


Epidemiological and Economic Evaluation of Alternative On-Farm Management Scenarios for Ovine Footrot in Switzerland.
Footrot is a multifactorial infectious disease mostly affecting sheep, caused by the bacteria Dichelobacter nodosus. It causes painful feet lesions resulting in animal welfare issues, weight loss, and reduced wool production, which leads to a considerable economic burden in animal production. In Switzerland, the disease is endemic and mandatory coordinated control programs exist only in some parts of the country. This study aimed to compare two nationwide control strategies and a no intervention scenario with the current situation, and to quantify their net economic effect. This was done by sequential application of a maximum entropy model (MEM), epidemiological simulation, and calculation of net economic effect using the net present value method. Building upon data from a questionnaire, the MEM revealed a nationwide footrot prevalence of 40.2%. Regional prevalence values were used as inputs for the epidemiological model. Under the application of the nationwide coordinated control program without (scenario B) and with (scenario C) improved diagnostics [polymerase chain reaction (PCR) test], the Swiss-wide prevalence decreased within 10 years to 14 and 5%, respectively. Contrary, an increase to 48% prevalence was observed when terminating the current control strategies (scenario D). Management costs included labor and material costs. Management benefits included reduction of fattening time and improved animal welfare, which is valued by Swiss consumers and therefore reduces societal costs. The net economic effect of the alternative scenarios B and C was positive, the one of scenario D was negative and over a period of 17 years quantified at CHF 422.3, 538.3, and -172.3 million (1 CHF = 1.040 US$), respectively. This implies that a systematic Swiss-wide management program under the application of the PCR diagnostic test is the most recommendable strategy for a cost-effective control of footrot in Switzerland.


Prostate cancer segmentation from MRI by a multistream fusion encoder.
Targeted prostate biopsy guided by multiparametric magnetic resonance imaging (mpMRI) detects more clinically significant lesions than conventional systemic biopsy. Lesion segmentation is required for planning MRI-targeted biopsies. The requirement for integrating image features available in T2-weighted and diffusion-weighted images poses a challenge in prostate lesion segmentation from mpMRI. A flexible and efficient multistream fusion encoder is proposed in this work to facilitate the multiscale fusion of features from multiple imaging streams. A patch-based loss function is introduced to improve the accuracy in segmenting small lesions. The proposed multistream encoder fuses features extracted in the three imaging streams at each layer of the network, thereby allowing improved feature maps to propagate downstream and benefit segmentation performance. The fusion is achieved through a spatial attention map generated by optimally weighting the contribution of the convolution outputs from each stream. This design provides flexibility for the network to highlight image modalities according to their relative influence on the segmentation performance. The encoder also performs multiscale integration by highlighting the input feature maps (low-level features) with the spatial attention maps generated from convolution outputs (high-level features). The Dice similarity coefficient (DSC), serving as a cost function, is less sensitive to incorrect segmentation for small lesions. We address this issue by introducing a patch-based loss function that provides an average of the DSCs obtained from local image patches. This local average DSC is equally sensitive to large and small lesions, as the patch-based DSCs associated with small and large lesions have equal weights in this average DSC. The framework was evaluated in 931 sets of images acquired in several clinical studies at two centers in Hong Kong and the United Kingdom. In particular, the training, validation, and test sets contain 615, 144, and 172 sets of images, respectively. The proposed framework outperformed single-stream networks and three recently proposed multistream networks, attaining F1 scores of 82.2 and 87.6% in the lesion and patient levels, respectively. The average inference time for an axial image was 11.8 ms. The accuracy and efficiency afforded by the proposed framework would accelerate the MRI interpretation workflow of MRI-targeted biopsy and focal therapies.


In situ production of active vitamin B12 in cereal matrices using Propionibacterium freudenreichii.
The in situ production of active vitamin B12 was investigated in aqueous cereal-based matrices with three strains of food-grade Propionibacterium freudenreichii. Matrices prepared from malted barley flour (33% w/v; BM), barley flour (6%; BF), and wheat aleurone (15%; AM) were fermented. The effect of cobalt and the lower ligand 5,6-dimethylbenzimidazole (DMBI) or its natural precursors (riboflavin and nicotinamide) on active B12 production was evaluated. Active B12 production was confirmed by UHPLC-UV-MS analysis. A B12 content of 12-37 μg·kg-1 was produced in BM; this content increased 10-fold with cobalt and reached 940-1,480 μg·kg-1 with both cobalt and DMBI. With riboflavin and nicotinamide, B12 production in cobalt-supplemented BM increased to 712 μg·kg-1. Approximately, 10 μg·kg-1 was achieved in BF and AM and was increased to 80 μg·kg-1 in BF and 260 μg·kg-1 in AM with cobalt and DMBI. The UHPLC and microbiological assay (MBA) results agreed when both cobalt and DMBI or riboflavin and nicotinamide were supplemented. However, MBA gave ca. 20%-40% higher results in BM and AM supplemented with cobalt, indicating the presence of human inactive analogues, such as pseudovitamin B12. This study demonstrates that cereal products can be naturally fortified with active B12 to a nutritionally relevant level by fermenting with P. freudenreichii.


Preliminary open trial of interpersonal counseling for subsyndromal depression following miscarriage.
Miscarriage occurs in 10-20% of clinically recognized pregnancies and is associated with two- to fourfold increases in depressive symptoms. No counseling programs for depressed miscarrying women have been manualized or evaluated for safety and efficacy. We investigated whether depressive symptoms decline substantially among miscarrying women receiving one to six weekly sessions of manualized, telephone-administered interpersonal counseling (IPC), a variant of interpersonal psychotherapy (IPT) in an open trial. Depressive symptom levels were measured with the Center for Epidemiologic Studies-Depression (CES-D) scale. Of 65 women evaluated, 24 were study eligible; 17 consented to participate. Change in symptom levels was evaluated by comparing baseline to postintervention CES-D scores in an intention to treat (ITT) sample (n=17) and a completer subsample (n=9). The latter sample comprised women reevaluated postintervention. In the ITT sample, the CES-D mean score declined from 25.4 to 18.8 [mean within-subject change=6.6, 95% confidence interval (CI)=1.4-11.6]; in the completer subsample, it declined from 23.6 to 11.2 (mean within-subject change=12.3, 95% CI=4.0-20.7). Findings from this small open trial suggest that IPC decreases depressive symptoms after miscarriage. A randomized, controlled trial of IPC's safety and efficacy with depressed miscarrying women is warranted.