Production of aberrant promoter transcripts contributes to methylation and silencing of unlinked homologous promoters in trans.
Previous work has suggested that de novo methylation of plant nuclear genes can be triggered by an RNA-DNA interaction. To test whether transcription of a promoter would induce de novo methylation and silencing of unlinked genes driven by the same promoter, a chimeric 'gene' consisting of a nopaline synthase promoter (NOSpro) positioned downstream of the cauliflower mosaic virus 35S promoter (35Spro) and flanked at the 3' end by a NOS terminator (NOSter) was constructed and introduced into the genome of a plant that normally expresses an unmethylated NOSpro-neomycinphosphotransferase (nptII) gene. Transformants were tested for kanamycin resistance and NOSpro RNA synthesis. Most produced a full-length polyadenylated NOSpro RNA, which did not induce silencing or methylation at the NOSpro-nptII target gene. One, however, contained truncated non-polyadenylated NOSpro RNA; in this plant, the NOSpro-nptII gene became silenced and methylated in the NOSpro region. Molecular analysis of the NOSpro silencing locus revealed two incomplete copies of the 35Spro-NOSpro gene arranged as an inverted repeat with NOSpro sequences at the center. Reducing NOSpro transcription by crossing a 35Spro-silencing locus partially reactivated nptII gene expression and decreased NOSpro methylation at the target locus, thus implicating aberrant NOSpro RNA in this trans-silencing phenomenon.


Optical manipulation of Rashba-split 2-dimensional electron gas.
In spintronics, the two main approaches to actively control the electrons' spin involve static magnetic or electric fields. An alternative avenue relies on the use of optical fields to generate spin currents, which can bolster spin-device performance, allowing for faster and more efficient logic. To date, research has mainly focused on the optical injection of spin currents through the photogalvanic effect, and little is known about the direct optical control of the intrinsic spin-splitting. To explore the optical manipulation of a material's spin properties, we consider the Rashba effect. Using time- and angle-resolved photoemission spectroscopy (TR-ARPES), we demonstrate that an optical excitation can tune the Rashba-induced spin splitting of a two-dimensional electron gas at the surface of Bi2Se3. We establish that light-induced photovoltage and charge carrier redistribution - which in concert modulate the Rashba spin-orbit coupling strength on a sub-picosecond timescale - can offer an unprecedented platform for achieving optically-driven spin logic devices.


Comments on the big-bang.
Is the big-bang hot, warm or cold? And are galactic masses determined by the interplay of gravitational and strong interactions in the very early universe?


In vitro assessment of the postantibiotic effect of lomefloxacin against gram-positive and gram-negative pathogens.
We evaluated the postantibiotic effect (PAE) of lomefloxacin, a new difluorinated quinolone, on multiply drug-resistant gram-positive and gram-negative clinical pathogens. Lomefloxacin induced a PAE of about 2 hours in gram-negative and gram-positive bacteria exposed for 1 hour to concentrations corresponding to four times their minimum inhibitory concentrations (MIC). PAE values (hours) ranged from 1.8 with Serratia marcescens to 2.5 with Staphylococcus aureus. No significant differences in PAE values were found for ciprofloxacin or ofloxacin against the same pathogens. The PAE was increased when the time of drug exposure was increased to 2 hours. These results indicate that lomefloxacin has a PAE equivalent to that of other fluoroquinolones.


Validity of MENARI plus (self-pulse assessment and clinical scoring) mobile apps for detecting atrial fibrillation in high-risk population.
Even before it is clinically diagnosed, atrial fibrillation (AF) can cause a stroke. This study validates self-pulse assessment and clinical scoring (MENARI Plus) based on android apps. The aim of this study was to examine the validity of AF screening using MENARI Plus compared with an ECG recording. We collected a total of 1385 subjects from high-risk population according to CHA2DS2-VASc score ≥2, attending 8 primary care centers (PCCs) in Malang between July 2021 and December 2021. Every participant underwent self-pulse assessment, and then was evaluated for MENARI Plus Score on android Apps. These cases had been classified as low or high probability for AF (cut-off score 7). After that, electrocardiography examinations were performed and classified with AF and Sinus Rhythm group. In this study, the mean age of these patients was 61.5 ± 6.9 years old. We found that 156/1385 (11%) patients had AF. There were 68/156 (43.5%) new cases of AF. The sensitivity for self-pulse palpation was 73.1% (95% CI: 68%-76%) and specificity was 68.3% (95% CI: 65%-72%). MENARI Plus had an area under the receiver operating curve (AUC) of 0.86 (95% CI: 0.82-0.89) with sensitivity per measurement occasion was (84%, 95% CI: 82%-88%) and specificity was (87.9%, 95% CI: 82%-90%). In this study, we found that MENARI Plus has high sensitivity and specificity for AF. It is therefore useful for ruling out AF. It may also be a useful screen that can be applied opportunistically for previously undetected AFs.


Pharmacokinetics of chromium-enriched yeast in rats following oral administration.
Chromium (Cr) is required for carbohydrate, lipid, and protein metabolisms in humans and animals. Cr insufficiency is associated with diabetes and cardiovascular disease. Chromium-enriched yeast (CrY) is a widely used Cr dietary supplement, but its pharmacokinetics remains unavailable. CrY was orally administered to rats at a single dose of 1 mg Cr/kg, and plasma Cr concentration at different time points was measured by inductively coupled plasma mass spectrometry. Pharmacokinetics of CrY in rats was well fitted to a non-compartmental model. Plasma Cr concentration reached the maximum of 8.68 ± 2.87 ng/mL at 0.25 h, and gradually decreased to 4.05 ± 0.47 ng/mL at 24 h. CrY was rapidly absorbed into the blood and was slowly eliminated after the oral administration, which could lead to the accumulation of Cr in vivo.


Development of an ICR mouse bioassay for toxicity evaluation in neurotoxic poisoning toxins-contaminated shellfish.
To develop an ICR (female) mouse bioassay (MBA) for toxicity confirmation and evaluation of neurotoxins (brevetoxins)-contaminated shellfish. Brevetoxins (BTX-B) as a causative agent of neurotoxic shellfish poisoning (NSP) under different shellfish matrices were intraperitoneally injected at different doses into mice to study their toxic effects and to differentiate the range of lethal and sublethal dosages. Their sensitivity and specificity were analyzed with 2 competitive ELISA kits for quantitative determination of standard BTX-B and dihydroBTX-B under different shellfish matrix-diluent combinations. Detection rates of MBA and two antibody-based assays for BTX-B from field NSP-positive shellfish samples were compared. BTX-B could be detected in shellfish tissues at concentration of 50-400 μg/100 g under shellfish matrix-Tween-saline media, which were appropriate to identify toxic shellfish at or above the regulatory limit (80 μg/100 g shellfish tissues). The LD50 identified was 455 mg/kg for BTX-B under general shellfish matrices (excluding oyster matrices) dissolved in Tween-saline. The presence of shellfish matrices, of oyster matrices in particular, retarded the occurrence of death and toxicity presentation in mice. Two antibody-based assays, even in the presence of different shellfish matrix-diluent combinations, showed acceptable results in quantifying BTX-B and dihydroBTX-B well below the regulatory limit. The two ELISA analyses agree favorably (correlation coefficient, r³⋝0.96; Student's t-tests, P>0.05) with the developed bioassay.


A solid-state NMR study of the interaction of fish antifreeze proteins with phospholipid membranes.
Fish antifreeze proteins and glycoproteins (AF(G)Ps) prevent ice crystal growth and are able to protect mammalian cells and tissues from hypothermic damage in the sub-zero Polar oceans. This protective mechanism is not fully understood, and further data is required to explain how AF(G)Ps are able to stabilize lipid membranes as they pass through their phase transition temperatures. Solid-state NMR spectroscopy was used as a direct method to study the interaction of the 37-residue alpha-helical type I AFP, TTTT, and the low molecular weight fraction glycoprotein, AFGP8, with dimyristoylphosphatidylcholine membranes above and below the gel-fluid phase transition temperature. In contrast to previous studies in fluid phase bilayers these experiments have provided direct information regarding both the mobility of the phosphate headgroups and perturbation of the acyl chains at a range of temperatures under identical conditions on the same sample. At 5 degrees C changes in the 2H and 31P spectra and a dramatic increase in the 31P T1 relaxation times were consistent with a significant disruption of the membrane by TTTT. Heating to 30 degrees C appeared to expel the peptide from the lipid and re-cooling showed that the interaction of TTTT was not reversible. By contrast, 31P spectra of the membranes with AFGP8 were consistent with interaction with the phosphate headgroups at both 5 and 30 degrees C. Although both peptides interact with the phospholipid bilayer surface, which may stabilize the membrane at lower temperatures, the longer 31P T1 values and the 2H NMR data obtained for TTTT compared with AFGP8 suggest that TTTT causes a greater reduction of phosphate headgroup mobility and has a greater effect on the lipid acyl chains at 5 degrees C.


Construction of block copolymers for the coordinated delivery of doxorubicin and magnetite nanocubes.
Multifunctional nanoparticles combine drug and imaging agent together to assign both therapeutic and diagnostic functions. However, particle aggregation/dissociation and/or major differences in the bio-distribution and targeting capability of drugs and imaging probes are main obstacles for the efficient, coordinated delivery of multiple agents, unless the different agents can be tightly bound and well-protected during their circulation in vivo. In this paper, we report the coordinated in vivo delivery of anti-cancer drugs and imaging agents by chemically loading doxorubicin and magnetite nanocubes (MNs) in the core of polymeric nanoparticles. Living polymerization, nitroxide-mediated radical polymerization (NMP), was applied to construct the optimal polymers to co-deliver doxorubicin and MNs. The resulting diblock polymers consisted of one block with triethylene glycol brushes and another block with carboxylic acid groups to bind doxorubicin and Fe3O4 MNs. The optimal polymer has narrow polydispersity (PDI=1.2) and high doxorubicin/MN loading (30wt.%/28wt.%). Core-shell particles were obtained with good stability and a suitable particle size of ~100nm. The doxorubicin and MNs loaded in this polymeric system showed highly coordinated bio-distribution in the balb/C mice model. This system may have important impact on the design of effective and stable dual-agent co-delivery systems.


Participants' Perceptions of Essential Coaching for Every Mother-a Canadian Text Message-Based Postpartum Program: Process Evaluation of a Randomized Controlled Trial.
"Essential Coaching for Every Mother" is a Canadian text message-based program that sends daily messages to mothers for 6 weeks after they give birth. There is a need to explore the program's effectiveness in terms of the participants' experience to guide refinement and modification. This study aimed to describe the process evaluation of the Essential Coaching for Every Mother randomized controlled trial through an evaluation of the research implementation extent and quality. Participants were recruited from Nova Scotia, Canada, between January 5 and August 1, 2021. Enrolled participants were randomized into the intervention or control group. Participants randomized to the intervention group received standard care along with the Essential Coaching for Every Mother program's text messages related to newborn and maternal care for the first 6 weeks after giving birth, while the control group received standard care. Usage data were collected from the SMS text message program used, and participants completed web-based questionnaires at 6 weeks after birth. Quantitative data and qualitative responses to open-ended questions were used to triangulate findings. Quantitative data were summarized using means, SDs, and percentages, as appropriate, while qualitative data were analyzed using thematic analysis. Of the 295 unique initial contacts, 150 mothers were eligible and completed the baseline survey to be enrolled in the study (intervention, n=78; control, n=72). Of those randomized into the intervention group, 75 (96%) completed the 6-week follow-up survey to provide feedback on the program. In total, 48 (62%) intervention participants received all messages as designed in the Essential Coaching for Every Mother program, with participants who enrolled late missing on average 4.7 (range 1-12) messages. Intervention participants reported an 89% satisfaction rate with the program, and 100% of participants would recommend the program to other new mothers. Participants liked how the program made them feel, the format, appropriate timing of messages, and content while disliking the frequency of messages and gaps in content. Participants also provided suggestions for future improvement. Our process evaluation has provided a comprehensive understanding of interest in the program as well as identified preference for program components. The findings of this study will be used to update future iterations of the Essential Coaching for Every Mother program. ClincalTrials.gov NCT04730570; https://clinicaltrials.gov/ct2/show/NCT04730570.


Self-association of disulfonated deuteroporphyrin and its esters in aqueous solution and photosensitized production of singlet oxygen by the dimers.
Dimerization of free acid and ester forms of disulfonated deuteroporphyrin is investigated in aqueous solution by absorbance and fluorescence spectroscopies. The dimerization equilibrium constant increases with the extent of esterification. In phosphate buffer saline (pH 7.4, 20 degrees C), it ranges from 1.4 x 10(6) M(-1) to 7.8 x 10(7) M(-1) for the free acid and the diethyl ester forms, respectively. The dimer formation is favored by an increase of ionic strength, as predicted by the Debye-Hückel law. The dimers display a marked shift to the blue of their Soret band. In agreement with the exciton model, a cofacial stacking of the molecules with some offset is postulated. The sulfonate groups on each molecule are likely to stand on opposite directions to reduce repulsion. Both the analysis of porphyrin self-association and careful examination of the fluorescence excitation spectra show that the dimers of disulfonated deuteroporphyrins do not fluoresce at all. The quantum yield of formation of singlet oxygen by the disulfonated deuteroporphyrins in deuterated methanol is 0.71, a value typical of monomers. In deuterated water, the yield is 0.44 for all the compounds studied though they are dimerized. The fact that nonfluorescent dimers of porphyrins can be efficient photosensitizers is emphasized.


Effect of soil amendments on trace element-mediated oxidative stress in plants: Meta-analysis and mechanistic interpretations.
During the last two decades, the use of soil amendments has gained high attention due to their role in governing trace element biogeochemistry in the soil. Majority of the studies dealing with soil amendments focused on the soil-plant transfer of trace elements, their compartmentation inside the plants and associated toxic effects. However, there is comparatively limited data regarding the effects of soil amendments on trace-element-induced oxidative stress (variations in stress and tolerance parameters) in plants. Therefore, this review, for the first time, critically elucidates the broad and specific trends in literature data of stress, tolerance and growth parameters under co-application of trace elements and soil amendments. For this purpose, a total of 3120 plant response items from literature data were collected/analyzed. The meta-analysis revealed an overall decrease in stress parameters (reactive oxygen species, membrane damage and lipid peroxidation), while an increase in tolerance parameters (antioxidants) and growth parameters (pigment contents). However, these general trends vary greatly with respect to different types of amendments, trace elements, plant species, plant organs and exposure cultures. In addition, the trends also varied for different types of response items of stress, tolerance and growth parameters (e.g., POD vs CAT, H2O2 vs O2). Manuscript critically discusses some mechanistic explanations for these general and specific trends in literature data. Finally, this review proposed key research gaps and important future perspectives. All the aspects discussed in this review have been strengthened with 23 Tables and 7 Figures. The research gaps and scientific queries established in this review based on meta-analysis of literature data will open new aspects of future research and discussion in the fields of ecotoxicology, stress physiology and remediation.


Quantitative thin-film x-ray microanalysis by STEM/HAADF: statistical analysis for precision and accuracy determination.
Silicon-germanium thin films have been analyzed by EDS microanalysis in a field emission gun scanning transmission electron microscope (FEG-STEM) equipped with a high angular dark-field detector (STEM/HAADF). Several spectra have been acquired in the same homogeneous area of the cross-sectioned sample by drift-corrected linescan acquisitions. The Ge concentrations and the local film thickness have been obtained by using a previously described Monte Carlo based "two tilt angles" method. Although the concentrations are in excellent agreement with the known values, the resulting confidence intervals are not as good as expected from the precision in beam positioning and tilt angle position and readout offered by our state-of-the-art microscope. The Gaussian shape of the SiKalpha and GeKalpha X-ray intensities allows one to use the parametric bootstrap method of statistics, whereby it becomes possible to perform the same quantitative analysis in sample regions of different compositions and thicknesses, but by doing only one measurement at the two angles.


Coil embolization for post-bypass aneurysm of middle meningeal artery for moyamoya disease - preservation of transdural anastomosis.
Middle meningeal artery (MMA) pseudoaneurysm following revascularization surgery for moyamoya disease (MMD) is rare. Here, a 29-year-old man presented with an MMA pseudoaneurysm after he underwent revascularization surgery (superficial temporal artery-to-middle cerebral artery bypass and encephalo-duro-myoarterio-pericranial synangiosis) for hemorrhagic MMD. At 3 months post-surgery, digital subtraction angiography showed a pseudoaneurysm in the right MMA. Transdural anastomosis to the parietal and occipital lobes was opacified at the distal MMA of the pseudoaneurysm. Intra-aneurysmal coil embolization was performed for preservation of transdural anastomosis. The postoperative course was uneventful. At 1 month post-embolization, angiography revealed an entirely occluded pseudoaneurysm. An increase in blood flow in the MMA due to bypass surgery may accelerate aneurysm development by increasing the hemodynamic stress. This case suggested that intra-aneurysmal embolization may be a potential treatment.


Privatising, liberalising and dividing a welfare state without affecting universality? Debunking the myths surrounding the rapid rise of private health insurance in Sweden.
The privatisation of provision and the emerging privatisation of funding, manifested in the rapid rise of private health insurance, are the most obvious signs that the universal, Swedish health system is gradually weakened. Meanwhile, the private welfare industry creates a neoliberal Newspeak where the burdening effects of the private insurance system on public healthcare are said to be unburdening, and where every step away from the principles of a universal welfare model is said to be in line with the principles of a universal welfare model. The language spoken by the private welfare industry spills over into authorities, journalists and scholars. In this article, I discuss, problematise and partially reject two research questions - Does VHI unburden the public health care system? and Are VHI holders less supportive of funding public health care? - where the authors fail to place development in the context of increased inequality and declining tax ratio, and where they use the welfare industry's definitions invented to blur the consequences of a parallel health system.


Physiologic effects of stress dose corticosteroids in in-hospital cardiac arrest (CORTICA): A randomized clinical trial.
Postresuscitation hemodynamics are associated with hospital mortality/functional outcome. We sought to determine whether low-dose steroids started during and continued after cardiopulmonary resuscitation (CPR) affect postresuscitation hemodynamics and other physiological variables in vasopressor-requiring, in-hospital cardiac arrest. We conducted a two-center, randomized, double-blind trial of patients with adrenaline (epinephrine)-requiring cardiac arrest. Patients were randomized to receive either methylprednisolone 40 mg (steroids group) or normal saline-placebo (control group) during the first CPR cycle post-enrollment. Postresuscitation shock was treated with hydrocortisone 240 mg daily for 7 days maximum and gradual taper (steroids group), or saline-placebo (control group). Primary outcomes were arterial pressure and central-venous oxygen saturation (ScvO2) within 72 hours post-ROSC. Eighty nine of 98 controls and 80 of 86 steroids group patients with ROSC were treated as randomized. Primary outcome data were collected from 100 patients with ROSC (control, n = 54; steroids, n = 46). In intention-to-treat mixed-model analyses, there was no significant effect of group on arterial pressure, marginal mean (95% confidence interval) for mean arterial pressure, steroids vs. control: 74 (68-80) vs. 72 (66-79) mmHg] and ScvO2 [71 (68-75)% vs. 69 (65-73)%], cardiac index [2.8 (2.5-3.1) vs. 2.9 (2.5-3.2) L/min/m2], and serum cytokine concentrations [e.g. interleukin-6, 89.1 (42.8-133.9) vs. 75.7 (52.1-152.3) pg/mL] determined within 72 hours post-ROSC (P = 0.12-0.86). There was no between-group difference in body temperature, echocardiographic variables, prefrontal blood flow index/cerebral autoregulation, organ failure-free days, and hazard for poor in-hospital/functional outcome, and adverse events (P = 0.08->0.99). Our results do not support the use of low-dose corticosteroids in in-hospital cardiac arrest.Trial Registration:ClinicalTrials.gov number: NCT02790788 ( https://www.clinicaltrials.gov ).


[Cancer prevention of the skin].
Skin cancer is the most common human carcinoma. There has been a dramatic increase of the incidence over the last decades. This trend is very likely caused by the increased UV-light exposition of the population. Whereas basalioma and spinalioma as the most frequent types of skin cancer have a low mortality, the bad prognosis of malignant melanoma is the reason for the 100% increase of the mortality rate over the last ten years. Cancer prophylaxis means the early detection of precancerous or suspect lesions. Popular information on the risk and a more generous indication for excision are the best instruments to lower the mortality of skin cancer.


Reduced content of α-synuclein in peripheral blood leukocytes of patients with LRRK2-associated Parkinson's disease.
Measurement of α-synuclein level in the peripheral blood was proposed as a diagnostic test for Parkinson's disease. However, the results of these studies remain contradictory, probably because the examined samples included patients with different etiology of Parkinson's disease. To verify this assumption we studied the levels of α-synuclein in peripheral blood leukocytes of patients with Parkinson's disease associated with mutations in the gene of leucine-rich kinase 2 (LRRK2). The mean α-synuclein level was significantly lower in patients with LRRK2-associated Parkinson's disease (N=8) than in patients with sporadic form of the disease (N=33; p<0.02) and in controls (N=18; p<0.05). On the other hand, we found no differences in the level of α-synuclein level between patients with sporadic form of the disease and controls. We hypothesize that the level of α-synuclein in the peripheral blood largely depends on the etiology of the disease and cannot be used as a universal diagnostic test for Parkinson's disease.


New catalytic ultrasound method for derivatization of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid in urine, with analysis by GC-MS/MS.
A new procedure is described for the derivatization by silylation of 11-nor-Δ(9)-tetrahydrocannabinol-9-carboxylic acid (THCCOOH) present in urine, followed by analysis using gas chromatography-tandem mass spectrometry. A conventional procedure for derivatization of the analyte was evaluated using two types of experimental design. A 2(3) factorial design considered the parameters temperature, reaction time, and the solvent/derivatization agent ratio. A central composite design (CCD) was applied to optimize the values of the significant variables. The optimum conditions were a reaction temperature of 50 °C, a reaction time of 30 min, and a BSTFA/acetone ratio of 40:20. The use of imidazole as a catalyst, together with ultrasonication, reduced the reaction time to 5 min and increased the efficiency of derivatization of THCCOOH, compared with the conventional method. The operating conditions of the tandem mass spectrometer were also optimized. The method was linear in the concentration range 1-50 ng mL(-1) (R(2) = 0.9951). Intra- and inter-day precisions were 7.7-12.3% and 11.1-13.9%, respectively, recoveries ranged between 91 ± 8% and 101 ± 12%, accuracy (as % bias) was between -11.7% and +0.7%, and limits of detection and quantification were 0.5 and 1.0 ng mL(-1), respectively.


Acute pesticide poisoning and pesticide registration in Central America.
The International Code of Conduct on the Distribution and Use of Pesticides of the Food and Agriculture Organization (FAO) of the United Nations has been for 20 years the most acknowledged international initiative for reducing negative impact from pesticide use in developing countries. We analyzed pesticide use and poisoning in Central America, particularly in Costa Rica and Nicaragua, and evaluated whether registration decisions are based on such data, in accordance with the FAO Code. Extensive use of very hazardous pesticides continues in Central America and so do poisonings with organophosphates, carbamates, endosulfan and paraquat as the main causative agents. Central American governments do not carry out or commission scientific risk assessments. Instead, guidelines from international agencies are followed for risk management through the registration process. Documentation of pesticide poisonings during several decades never induced any decision to ban or restrict a pesticide. However, based on the official surveillance systems, in 2000, the ministers of health of the seven Central American countries agreed to ban or restrict twelve of these pesticides. Now, almost 4 years later, restrictions have been implemented in El Salvador and in Nicaragua public debate is ongoing. Chemical and agricultural industries do not withdraw problematic pesticides voluntarily. In conclusion, the registration processes in Central America do not comply satisfactorily with the FAO Code. However, international regulatory guidelines are important in developing countries, and international agencies should strongly extend its scope and influence, limiting industry involvement. Profound changes in international and national agricultural policies, steering towards sustainable agriculture based on non-chemical pest management, are the only way to reduce poisonings.


Construction of artificial promoters sensitively responsive to sonication in vitro.
To develop artificial promoters that are activated in response to sonication and to determine these properties in vitro. The binding sites of four transcription factors (nuclear factor-kappa B, activating protein-1, nuclear factor-Y, and CArG element binding factor A) that are activated by oxidative stress were randomly ligated and linked to a TATA-box sequence to control the luciferase gene located downstream. Transiently transfected HeLa cells from human cervical cancer with a plasmid vector containing such a gene cassette were exposed to sonication, and enhancement of luciferase expression was assessed by dual luciferase assay. Of 62 promoters constructed, two promoters, designated clone 31 and clone 62 promoters, showed a more than tenfold enhancement 6 h after sonication with 1-MHz ultrasound at 1.0 W/cm(2) for 60 s. These promoters were activated in a dose-dependent manner with the intensity and duration of sonication. The activation was attenuated by addition of dimethyl sulfoxide, an antioxidant, suggesting that oxidative stress was involved. The clone 31 promoter responded to each of two serial sonications. When sonicated 24 h after the first sonication, the peak of promoter enhancement was higher than that after the first sonication. A promoter sensitively responsive to sonication was constructed using the above method, possibly leading to the construction of a promoter of interest that could be applied for clinical use.


Comparison of intravenous anisoylated plasminogen streptokinase activator complex and intracoronary streptokinase in acute myocardial infarction.
Coronary angiography was used to compare the efficacy of anisoylated plasminogen streptokinase activator complex (APSAC) administered intravenously and streptokinase given by intracoronary infusion in inducing reperfusion in patients with a proven acute myocardial infarction. Forty-two patients received 30 U of APSAC intravenously over 5 minutes and 43 patients received 250,000 IU of streptokinase given via intracoronary infusion over 90 minutes, after occlusion of the infarct-related vessel was demonstrated by angiography. Reperfusion was achieved in 23 (64%) of 36 patients (mean time to reperfusion 46 minutes) treated with APSAC and 25 (67%) of 37 patients (mean time to reperfusion 45 minutes) treated with intracoronary streptokinase, who were angiographically evaluated 90 minutes after the start of treatment. Twenty-four hours after treatment, reocclusion had occurred in 1 (5%) of 22 patients in the APSAC group and in 3 (13%) of 23 patients in the streptokinase group. No major bleeding was observed in either treatment group despite a similar systemic lytic state that lasted for up to 48 hours. Two patients treated with APSAC died after severe left ventricular failure unrelated to therapy. The results indicate that APSAC given intravenously is as effective as streptokinase given intracoronary in producing thrombolysis in acute myocardial infarction. The major advantages of APSAC are its rapid and convenient administration by a single intravenous injection, the low rate of arterial reocclusion and good patient tolerance.


Near-field interference for the unidirectional excitation of electromagnetic guided modes.
Wave interference is a fundamental manifestation of the superposition principle with numerous applications. Although in conventional optics, interference occurs between waves undergoing different phase advances during propagation, we show that the vectorial structure of the near field of an emitter is essential for controlling its radiation as it interferes with itself on interaction with a mediating object. We demonstrate that the near-field interference of a circularly polarized dipole results in the unidirectional excitation of guided electromagnetic modes in the near field, with no preferred far-field radiation direction. By mimicking the dipole with a single illuminated slit in a gold film, we measured unidirectional surface-plasmon excitation in a spatially symmetric structure. The surface wave direction is switchable with the polarization.


Design, synthesis and biological evaluation of mannosyl triazoles as FimH antagonists.
Urinary tract infection (UTI) caused by uropathogenic Escherichia coli (UPEC) is one of the most prevalent infectious diseases. Particularly affected are women, who have a 40-50% risk to experience at least one symptomatic UTI episode at some time during their life. In the initial step of the infection, the lectin FimH, located at the tip of bacterial pili, interacts with the high-mannosylated uroplakin Ia glycoprotein on the urinary bladder mucosa. This interaction is critical for the ability of UPEC to colonize and invade the bladder epithelium. X-ray structures of FimH co-crystallized with two different ligands, the physiological binding epitope oligomannose-3 and the antagonist biphenyl α-D-mannoside 4a revealed different binding modes, an in-docking-mode and an out-docking-mode, respectively. To accomplish the in-docking-mode, that is the docking mode where the ligand is hosted by the so-called tyrosine gate, FimH antagonists with increased flexibility were designed and synthesized. All derivatives 5-8 showed nanomolar affinities, but only one representative, the 4-pyridiyl derivative 5j, was as potent as the reference compound n-heptyl α-D-mannoside (1b). Furthermore, a loss of affinity was observed for C-glycosides and derivatives where the triazole aglycone is directly N-linked to the anomeric center. A conformational analysis by NMR revealed that the triazolyl-methyl-C-mannosides 8 adopt an unusual (1)C(4) chair conformation, explaining the comparably lower affinity of these compounds. Furthermore, to address the druglikeness of this new class of FimH antagonists, selected pharmacokinetic parameters, which are critical for oral bioavailability (lipophilicity, solubility, and membrane permeation), were determined.


The trithorax group gene osa encodes an ARID-domain protein that genetically interacts with the brahma chromatin-remodeling factor to regulate transcription.
The trithorax group gene brahma (brm) encodes the ATPase subunit of a chromatin-remodeling complex involved in homeotic gene regulation. We report here that brm interacts with another trithorax group gene, osa, to regulate the expression of the Antennapedia P2 promoter. Regulation of Antennapedia by BRM and OSA proteins requires sequences 5' to the P2 promoter. Loss of maternal osa function causes severe segmentation defects, indicating that the function of osa is not limited to homeotic gene regulation. The OSA protein contains an ARID domain, a DNA-binding domain also present in the yeast SWI1 and Drosophila DRI proteins. We propose that the OSA protein may target the BRM complex to Antennapedia and other regulated genes.


Sebaceous lymphadenocarcinoma of salivary glands.
Primary sebaceous neoplasms of the salivary glands are extremely rare occurrences; furthermore, sebaceous lymphadenocarcinoma has only been reported in three patients. We report a case of sebaceous lymphadenocarcinoma arising in a lymphadenoma of the parotid gland. The patient was a 55-year-old man who presented with a parotid mass of 3 years' duration. Histologically, the lesion consisted of a sebaceous lymphadenoma with transition to a sebaceous carcinoma. The cytologic touch-preparation at the time of frozen section showed clusters of benign sebaceous cells in a rich lymphocytic background together with tridimensional clusters of malignant epithelial cells, strongly raising the suspicion of a malignant neoplasm arising in a benign sebaceous lesion. Malignant transformation of the sebaceous lymphadenoma, although rare, should be considered in enlarging, locally invasive parotid lesions, considering that clinical behavior and prognosis will be determined by the nature of the malignant component.


Minimally invasive surgery of mitral valve (MIS-MV).
Following the revision of the therapeutic guideline of ACC/AHA in (Circulation 114:450-527, 2006), the incidence of mitral valve repair in asymptomatic patients with moderate or severe mitral valve regurgitation has increased. For mitral valve repair, the quality and outcomes as well as lower invasive procedure are important to obtain the confidence of cardiologists and ensure request of early phase operation from cardiologists. With recent innovations of technologies and the development of revolutionary techniques, minimally invasive surgery of the mitral valve (MIS-MV) has become a widespread surgical option of mitral valve repair. It is vital, however, that careful preoperative assessment, and planning of the approach and perfusion strategy are put in place to perform MIS-MV safely.


Cerebral White Matter Hypoperfusion Increases with Small-Vessel Disease Burden. Data From the Third International Stroke Trial.
Leukoaraiosis is associated with impaired cerebral perfusion, but the effect of individual and combined small-vessel disease (SVD) features on white matter perfusion is unclear. We studied patients recruited with perfusion imaging in the Third International Stroke Trial. We rated individual SVD features (leukoaraiosis, lacunes) and brain atrophy on baseline plain computed tomography or magnetic resonance imaging. Separately, we assessed white matter at the level of the lateral ventricles in the cerebral hemisphere contralateral to the stroke for visible areas of hypoperfusion (present or absent) on 4 time-based perfusion imaging parameters. We examined associations between SVD features (individually and summed) and presence of hypoperfusion using logistic regression adjusted for age, sex, baseline National Institutes of Health Stroke Scale, hypertension, and diabetes. A total of 115 patients with median (interquartile range) age of 81 (72-86) years, 78 (52%) of which were male, had complete perfusion data. Hypoperfusion was most frequent on mean transit time (MTT; 63 patients, 55%) and least frequent on time to maximum flow (19 patients, 17%). The SVD score showed stronger independent associations with hypoperfusion (e.g., MTT, odds ratio [OR] = 2.80; 95% confidence interval [CI] = 1.56-5.03) than individual SVD markers (e.g., white matter hypoattenuation score, MTT, OR = 1.49, 95% CI = 1.09-2.04). Baseline blood pressure did not differ by presence or absence of hypoperfusion or across strata of SVD score. Presence of white matter hypoperfusion increased with SVD summed score. The SVD summed score was associated with hypoperfusion more consistently than individual SVD features, providing validity to the SVD score concept. Increasing SVD burden indicates worse perfusion in the white matter.


Discovery of 5-substituent-N-arylbenzamide derivatives as potent, selective and orally bioavailable LRRK2 inhibitors.
Leucine-rich repeat kinase 2 (LRRK2) has been suggested as a potential therapeutic target for Parkinson's disease. Herein we report the discovery of 5-substituent-N-arylbenzamide derivatives as novel LRRK2 inhibitors. Extensive SAR study led to the discovery of compounds 8e, which demonstrated potent LRRK2 inhibition activity, high selectivity across the kinome, good brain exposure, and high oral bioavailability.


Venous thromboembolism after thoracic/thoracolumbar spinal fusion.
Venous thromboembolism (VTE), which includes deep venous thrombosis and pulmonary embolism, is a serious and potentially fatal surgical complication. The goal of our study was to examine preoperative characteristics, incidence, and outcomes of patients with VTE after elective thoracic/thoracolumbar level spine fusion. We identified 430,081 patients from the Nationwide Inpatient Sample database who underwent spinal fusion between 2002 and 2008. Patients undergoing thoracic/thoracolumbar level fusion (n = 8617) were found to have the greatest concurrent rate of VTE. We then performed multivariate analyses on this cohort to identify predictors of and outcomes after VTE in patients undergoing thoracic/thoracolumbar level fusion. The overall VTE rate in spinal fusion surgery was 0.40% (cervical = 0.22%, thoracic/thoracolumbar = 1.90%, lumbar/lumbosacral = 0.49%, re-fusions = 0.64%, and fusions not otherwise specified = 0.84%). On multivariate logistic regression analysis of patients undergoing spinal fusion at the thoracic/thoracolumbar level, increasing age, Medicare insurance coverage (vs. private insurance), urban teaching hospital (vs. urban nonteaching hospital), combined anterior/posterior surgical approach (vs. posterior-only approach), and the presence of congestive heart failure or weight loss (Elixhauser comorbidity groups) were each independently associated with an increased odds ratio of VTE complication. VTE after thoracic/thoracolumbar surgery was significantly associated with longer hospital stays (16.6 vs. 6.74 days), increased total hospital costs ($260,208 vs. $115,474), and increased mortality (4.33% vs. 0.33%). Multivariate logistic regression analysis reveals age, insurance status, hospital type, combined anterior/posterior surgical approach, and the presence of congestive heart failure or weight loss to be independently associated with an increased odds ratio of VTE complication. This complication is associated with increased hospital costs, length of stay, and overall mortality.


Effect of topical anesthetic agents and ethanol on corneoepithelial wound healing in an ex vivo whole-globe porcine model.
To assess the impact of topical anesthetic agents and ethanol on ocular surface wound healing using an ex vivo whole-globe porcine model. Department of Ophthalmology, Inselspital, University of Bern, Bern, Switzerland. Experimental study. Standardized corneoepithelial lesions (5.0 mm diameter, 40 μm depth) were created with excimer laser light in freshly enucleated porcine eyes. The globes (6 per group) were exposed to different concentrations of ethanol (2.0% to 99.0%), cocaine (2.0% to 10.0%), procaine hydrochloride (0.4%), tetracaine (0.5% to 1.0%), or lidocaine (2.0%), 3 drops/hour for 3 hours. Control solutions were physiologic saline, balanced salt solution, and tissue-culture medium. After 20 to 26 hours, wound-healing response was compared by measuring the diameter of each corneoepithelial lesion. The mean diameter of corneoepithelial lesions exposed to physiologic saline decreased from 4.78 mm ± 0.19 (SD) to 4.44 ± 0.17 mm between 20 and 26 hours. After 24 hours, the mean lesion size, compared with physiological saline, was larger after cocaine 5.0% (5.20 ± 0.26 mm) and 10.0% (5.39 ± 0.12 mm), tetracaine 0.5% (5.59 ± 0.35 mm) and 1.0% (5.55 ± 0.27 mm), and procaine hydrochloride 0.4% (5.76 ± 0.12 mm), but not after lidocaine 2.0% (5.01 ± 0.17 mm). Balanced salt solution, tissue-culture medium, ethanol 2.0% to 99.0%, and cocaine 2.0% did not inhibit the wound-healing response. In an ex vivo whole-globe porcine model, lidocaine 2.0% and cocaine 2.0% were the least toxic anesthetic agents. At all concentrations, ethanol had no impact on wound healing. No author has a financial or proprietary interest in any material or method mentioned.


Identification, purification, and characterization of a stilbenedisulfonate binding glycoprotein from canine kidney brush border membranes. A candidate for a renal anion exchanger.
Canine renal brush border membrane proteins that bind stilbenedisulfonate inhibitors of anion exchange were identified by affinity chromatography. A 130-kDa integral membrane glycoprotein from brush border membrane was shown to bind specifically to 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonate immobilized on Affi-Gel 102 resin. The bound protein could be eluted effectively with 1 mM 4-benzamido-4'-aminostilbene-2,2'-disulfonate (BADS). The 130-kDa protein did not bind to the affinity resin in the presence of 1 mM BADS or when the solubilized extract was covalently labeled with 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS). This protein was labeled with [3H]H2DIDS, and the labeling was prevented by BADS. The 130-kDa protein did not cross-react with antibody raised against human or dog erythrocyte Band 3 protein. The 130-kDa protein was accessible to proteinase K and chymotrypsin digestion in vesicles but not to trypsin. The 130-kDa protein was sensitive to endo-beta-N-acetylglucosaminidase F treatment both in the solubilized state and in brush border membrane vesicles showing that it was a glycoprotein and that the carbohydrate was on the exterior of the vesicles. This glycoprotein was resistant to endo-beta-N-acetylglucosaminidase H treatment suggesting a complex-type carbohydrate structure. The protein bound concanavalin A, wheat germ agglutinin, and Ricinus communis lectins, and it could be purified using wheat germ agglutinin-agarose.


Methods of Analysis: Functional MRI for Presurgical Planning.
There are many technical and nontechnical steps involved in a successful clinical functional MRI (fMRI) scan. The output from scanning and analysis can only be as good as the input, so task instruction and rehearsal are the most important steps during an clinical fMRI procedure. Properly pre-processed data significantly affects statistical analysis, which has a great impact on image interpretation. Even though there is general agreement on how to process clinical fMRI data, such as algorithms for head motion detection and correction, the theory and practicalities associated with data processing remain complex and constantly evolving.


Psoriasis and psychiatry: an update.
Psychosocial factors are important in the onset and/or exacerbation of psoriasis in 40%-80% of cases. Yet psoriasis has received little attention in the recent psychiatric literature. A subgroup of psoriatics appear to be "stress reactors" and these patients may have a better long-term prognosis. Identification of such patients early in the course of treatment and incorporation of specific psychosocial interventions in their overall treatment regimen may improve the course of illness. Psoriasis has also been associated with suicide and an increased prevalence of alcoholism. The disturbances in body image perception and the effect of psoriasis on interpersonal, social, and occupational functioning can further contribute to the overall morbidity, especially if psoriasis first occurs during a developmentally critical period like adolescence. Certain biochemical and physiologic correlates of psoriasis of interest to the psychiatrist such as exacerbation of psoriasis with lithium therapy and increased cutaneous blood flow are discussed. Finally, some practical guidelines are provided for psychosocial interventions in psoriasis.


Surgeon volume and outcomes in benign hysterectomy.
Annual surgeon case volume has been linked to patient outcome in a variety of surgical fields, although limited data focus on gynecologic surgery performed by general gynecologists. Herein we review the literature addressing the associations between intraoperative injury, postoperative morbidity, and resource use among surgeons performing a low vs high volume of hysterectomies. Although study design and populations differ, individual and composite morbidity outcomes consistently favored high-volume surgeons. Given the growing emphasis on competency-based evaluation in surgery, gynecology departments may soon consider volume requirements a component of privileging.


MPI-CDG from a hepatic perspective: Report of two Egyptian cases and review of literature.
MPI-CDG is a rare congenital disorder of glycosylation (CDG) which presents with hepato-gastrointestinal symptoms and hypoglycemia. We report on hepatic evaluation of two pediatric patients who presented to us with gastrointestinal symptoms. Analysis of carbohydrate deficient transferrin (CDT) showed a Type 1 pattern and molecular analysis confirmed the diagnosis of MPI-CDG. Oral mannose therapy was markedly effective in one patient but was only partially effective in the other who showed progressive portal hypertension.


Normal growth of the fetal biparietal diameter and the abdominal diameter in a longitudinal study. An evaluation of the two parameters in predicting fetal weight.
Normal growth curves of the fetal biparietal diameter (BPD) and abdominal diameter (AD) were measured by ultrasound in 41 normal pregnant women who had had regular menstruation with a known last menstrual period. The women were studied longitudinally from the 13th - 14th week of gestation and thereafter every 2-4 weeks until spontaneous onset of labor. The BPD curve proved to be uniform, with a deviation of 4.7 days (1 SD) before the 21st week. A 3rd-degree polynomial was found to be adequate to describe the results for BPD and AD. The value of longitudinal studies is emphasized by the fact that by using the same curve with individual plateaus rather than a common curve, as most often reported in the literature, it is possible to reduce the variance for BPD and AD by 54% and 40% respectively. There was a difference of up to 7 days for the mean BPD value prior to the 24th week of gestation between the present results and previously published normal curves collected in cross-sectional investigations. When calculating the mean fetal weight on the basis of measuring the BPD and AD, we found a linear correlation between the estimated fetal weight in the 3rd trimester and the duration of pregnancy (r = 0.99, p less than 0.001). The mean percentual difference in weight between the estimated and the actual weight was 1.2% +/- 10.5% (1 SD), which is acceptable for routine clinical use.


Metaphyseal bone loss in revision knee arthroplasty.
The etiology of bone loss encountered during revision total knee arthroplasty (TKA) is often multifactorial and can include stress shielding, osteolysis, osteonecrosis, infection, mechanical loss due to a grossly loose implant, and iatrogenic loss at the time of implant resection. Selection of the reconstructive technique(s) to manage bone deficiency is determined by the location and magnitude of bone loss, ligament integrity, surgeon experience, and patient factors including the potential for additional revision, functional demand, and comorbidities. Smaller, contained defects are reliably managed with bone graft, cement augmented with screw fixation, or modular augments. Large metaphyseal defects require more extensive reconstruction such as impaction bone grafting with or without mesh augmentation, prosthetic augmentation, use of bulk structural allografts, or use of metaphyseal cones or sleeves. While each technique has advantages and disadvantages, the most optimal method for reconstruction of large metaphyseal bone defects during revision TKA is not clearly established.


Patient-reported outcomes in studies of complementary and alternative medicine: problems, solutions, and future directions.
Patient-reported outcome (PRO) measures are frequently used to assess therapeutic efficacy and effectiveness of complementary and alternative medicine (CAM). Although CAM investigators are increasingly making use of valid, self-report instruments to assess patient-relevant outcomes, the sheer number of available instruments poses challenges. Two of the more pressing issues are discussed: the lack of guidance for selecting measures and the limited attention paid to the clinical meaningfulness of PRO results. Solutions are offered that may support selection and standardization of outcome measures for future CAM studies. This includes testing of tools from the National Institutes of Health's Patient-Reported Outcomes Measurement Information System (PROMIS). Increased standardization of outcome measurement in CAM studies will allow for more cross-study comparisons and facilitate the statistical pooling of results, ultimately leading to a more informative evidence base.


Separate brain potential characteristics in children with reading disability and attention deficit disorder: relevance-independent effects.
The effects of reading disability (RD) and attention deficit disorder (ADD) on event-related potentials (ERPs) were investigated in 52 boys between 8 and 12 years of age. There were four groups: 25 children without RD divided into two groups (17 without ADD and 8 with ADD) and 27 children with RD divided into two groups (11 without ADD and 16 with ADD). The children participated in three tasks ("games") designed to assess selective attention to the color black (vs white), to any of two letters (vs. two patterns), and to any of 12 letters (vs. 12 patterns). ERPs were recorded over the left and right occipital, central, and frontal hemispheres. Children with RD as compared to those without RD were characterized by the following ERPs: (1) a smaller amplitude positive wave at about 240 msec (P240) over the left central hemisphere: (2) a smaller amplitude positive wave at about 500 msec (P500) over the right central hemisphere: (3) a larger P500 over the right central hemisphere: (3) a larger P500 over both left and right occipital hemispheres: and (4) smaller within-subject-and-condition variability of ERP waveform. These effects did not differ significantly for the three games and, therefore, were not specific to letter processing per se. The effects of RD did not interact with the effects of ADD for the most part. The ERPs clearly indicated these two disorders, in part, involve different underlying brain processes.


Intra- and interhemispheric EEG differences quantified by spectral analysis. Comparative study of two groups of schizophrenics and a control group.
In this work we have studied comparatively the relationships between alpha intensity, alpha frequency, root-mean-square amplitude and their standard deviations, versus the location of the four recorded EEG channels: left and right rolando-parietal, left and right parieto-occipital. Twenty-four spectral parameters were computed for each 5-min EEG recording, in the eyes closed situation. The hebephrenic group (36 EEGs from six patients) presented higher values of alpha intensity and RMS amplitudes with low coefficient of variation when compared with the other groups. The left/right rolando-parietal amplitude ratio was 0.73 versus 1.52 for the parieto-occipital ratio. An amplitude hypovariability in the central regions, probably associated with hyperarousal, especially in the left hemisphere, can then be observed in hebephrenics, together with high alpha intensity on the left parieto-occipital area. The two groups of schizophrenics differ from the control group (27 EEGs from 12 subjects) in terms of spectral parameters, the hebephrenic group presenting a possible interhemispheric dysfunction.


Reactive arthritis occurring after COVID-19 infection: a narrative review.
Reactive arthritis is acute aseptic arthritis occurring 1 to 4 weeks after a distant infection in a genetically predisposed individual. It may occur after COVID-19 infection. We summarize, in this article, the current findings of reactive arthritis following COVID-19 infection. A literature search has been performed from December 2019 to December 2021. We included case reports of reactive arthritis occurring after COVID-19 infection. We collected demographic, clinical, and paraclinical data. A total of 22 articles were reviewed. There were 14 men and 11 women with a mean age of 44.96 + 17.47 years. Oligoarticular involvement of the lower limbs was the most frequent clinical presentation. The time between arthritis and COVID infection ranged from 6 to 48 days. The diagnosis was based on clinical and laboratory findings. The pharmacological management was based on non-steroidal anti-inflammatory drugs in 20 cases. Systemic or local steroid therapy was indicated in 13 patients. Sulfasalazine was indicated in two cases. Alleviation of symptoms and recovery were noted in 22 cases. The mean duration of the clinical resolution was 16 + 57 days. The diagnosis of reactive arthritis should be considered in patients with a new onset of arthritis following COVID-19 infection. Its mechanism is still unclear.


Drug delivery's quest for polymers: Where are the frontiers?
Since the legendary 1964 article of Folkman and Long entitled "The use of silicone rubber as a carrier for prolonged drug therapy" the role of polymers in controlled drug delivery has come a long way. Today it is evident that polymers play a crucial if not the prime role in this field. The latest boost owes to the interest in drug delivery for the purpose of tissue engineering in regenerative medicine. The focus of this commentary is on a selection of general and personal observations that are characteristic for the current state of polymer therapeutics and carriers. It briefly highlights selected examples for the long march of synthetic polymer-drug conjugates from bench to bedside, comments on the ambivalence of selected polymers as inert excipients versus biological response modifiers, and on the yet unsolved dilemma of cationic polymers for the delivery of nucleic acid therapeutics. Further subjects are the complex design of multifunctional polymeric carriers including recent concepts towards functional supramolecular polymers, as well as observations on stimuli-sensitive polymers and the currently ongoing trend towards natural and naturally-derived biopolymers. The final topic is the discovery and early development of a novel type of biodegradable polyesters for parenteral use. Altogether, it is not the basic and applied research in polymer therapeutics and carriers, but the translational process that is the key hurdle to proceed towards an authoritative approval of new polymer therapeutics and carriers.


Persistent reversed end-diastolic flow of the middle cerebral artery: A rare and concerning finding.
Fetal reversed end-diastolic flow of the middle cerebral artery is a rare ultrasound finding associated with pathological fetal conditions. Herein, we report the case of a fetus presenting with reversed end-diastolic flow of the middle cerebral artery caused by extensive intracranial hemorrhage from maternal warfarin therapy. From a literature review, we present the clinical findings, etiologies, and outcomes of cases with fetal reversed end-diastolic flow of the middle cerebral artery.


The covalent differences between bovine alpha- and beta-thrombin. A structural explanation for the changes in catalytic activity.
The partial covalent structure of bovine beta-thrombin has been determined by the use of automated Edman degradation and carboxypeptidase digestion of the component polypeptide chains separated by gel filtration following either reduction and carboxymethylation or performic acid oxidation. beta-Thrombin has been found to contain three peptide chains derived by proteolysis of the parent alpha-thrombin molecule. The A chain of alpha-thrombin has been cleaved at two points yielding a peptide (A1 chain) which contains 17 amino acids, beginning with threonine 14 and ending with lysine 30. The B chain of alpha-thrombin has been cleaved at two positions to yield a B1 chain which begins with the NH2-terminal isoleucine and terminates with lysine 65 and a B2 chain which begins with lysine 74 and continues through COOH-terminal serine 259. The A1 chain and B2 chain are linked by a disulfide bridge. Although there is no evidence for a covalent bond between the B1 chain and the B2-A1 chains, the B1 chain is tightly bound to the remainder of the molecule, for separation is achieved only under denaturing conditions.


Molecular size and molecular structure: Discriminating their changes upon chemical reactions in terms of information entropy.
Structural descriptors take the central place in the digitalization of chemical reactions. Information entropy is one of such descriptors that has been a seminal for numerous derivative indices. Previously, we have studied the rules of calculating information entropies of molecular ensembles based on the corresponding values of constituting molecules and found that the complexity of the ensemble has the contributions from the molecular structure and the size of the molecules. Considering chemical reaction as the conversion of one molecular ensemble to another allows calculating the change in information entropy as well as its components associated with molecular-structure and molecular-size changes. We demonstrate that both total information entropy change and its contributions are characteristic for the selected classes of chemical reactions and exemplify this approach with the cycloaddition and exchange reactions widespread in organic chemistry.


Ecological Diversity of Bacterial Rhizomicrobiome Core during the Growth of Selected Wheat Cultivars.
One of the latest ecological concepts is the occurrence of a biased rhizosphere of microorganisms recruited mostly through interactions among various components of the rhizosphere, including plant roots and the bulk soil microbiome. We compared the diverse attributes of the core microbiome of wheat rhizosphere communities with wheat (W) and legume (L) forecrops determined by three different methods in this study (membership, composition, and functionality). The conclusions of the three methods of microbiome core definition suggest the presence of generalists, i.e., some representative microorganisms from Proteobacteria, Actinobacteria, Hypomicrobiaceae, Bradyrhizobiaceae, Sphingomonas sp., in the wheat rhizomicrobiome. The relative abundance of the core microbiome accounted for 0.1976% (W) and 0.334% (L)-membership method and 6.425% (W) and 4.253% (L)-composition method. Additionally, bacteria of the specialist group, such as Rhodoplanes sp., are functionally important in the rhizomicrobiome core. This small community is strongly connected with other microbes and is essential for maintenance of the sustainability of certain metabolic pathways.


Population expansion and gene flow in Giardia duodenalis as revealed by triosephosphate isomerase gene.
Giardia duodenalis is a protozoan parasite that can cause significant diarrhoeal diseases. Knowledge of population genetics is a prerequisite for ascertaining the invasion patterns of this parasite. In order to infer evolutionary patterns that could not be uncovered based on the morphological features, a population genetic study with the incorporation of molecular marker was carried out to access the genetic structure of G. duodenalis isolated from the Malaysian population and the global populations. A total of 154 samples positive for Giardia, collected from different Malaysian communities, were subjected to DNA amplification and sequencing targeting three genetic loci (tpi, gdh, and bg). The tpi sequences together with sequences from the global data obtained from the NCBI GenBank were used for genetic diversity analyses including identification of haplotypes, haplotype diversity, nucleotide diversity, Tajima's D and Fu and Li's D, gene flow and genetic differentiation tests. Analysis of the Malaysian and global data showed that assemblages A, B, and E (the most prevalent assemblages in humans and animals), have different levels of genetic diversity. Assemblage B had the highest level of both haplotype diversity and nucleotide diversity, followed by assemblage E. The analysis also revealed population expansion and high gene flow in all assemblages. No clear genetic structure was observed across five continents (i.e., the Americas, Europe, Asia, Australia and Africa). However, median joining network of assemblage B formed a cluster that was exclusively isolated from Asia while other haplotypes were well dispersed across the continents. This study provides new insight into the genetic diversity of Giardia assemblages in different geographical regions. The significant result shown by gene flow and genetic differentiation analyses as well as test of neutrality among the populations should have brought a clearer picture to the dynamics and distribution of Giardia infection.


Outbreak investigation including molecular characterization of community associated methicillin-resistant Staphylococcus aureus in a primary and secondary school in Eastern Switzerland.
At our tertiary children's hospital, infections with newly detected methicillin-resistant Staphylococcus aureus (MRSA) among children attending primary (age 6-12 years) and secondary school (age 13-16 years) nearly doubled in 2018 compared to previous years. This observation initiated an epidemiological outbreak investigation including phenotypic (susceptibility testing) and genotypic (whole genome sequencing) characterization of the isolates. In addition, a cross-sectional study was conducted to determine source of the outbreak, colonization frequency and to identify risk factors for transmission using a questionnaire. As a result, 49 individuals were detected with 57 corresponding isolates. Based on the case definition combined with whole genome sequencing, a core cluster was identified that shared common genetic features and a similar antimicrobial susceptibility pattern (efflux-mediated macrolide resistance, tetracycline susceptibility along with presence of Panton-Valentine leukocidin). Epidemiologic evaluation identified a distinct school as a common risk factor. However, the source of the clustered infections within that school could not be further specified. No further cases could be detected after decolonization of infected and colonized children.


5'-terminal caps of snRNAs are accessible for reaction with 2,2,7-trimethylguanosine-specific antibody in intact snRNPs.
Immune precipitation assays with antibodies specific for 2,2,7-trimethylguanosine (m2,2,7(3)G) have been used to study the accessibility of the 5'-terminal m2,2,7(3)G-containing caps of eucaryotic small nuclear RNAs (snRNAs) either as naked RNAs or in intact small nuclear ribonucleoprotein (snRNPs). The antibody selectively precipitates snRNA species U1a, U1b, U2, U4, and U5 from total deproteinized RNA isolated from Ehrlich ascites cells. Binding by the antibody occurs via the m2,2,7(3)G moiety of the snRNAs' caps, since complex formation with the antibody can be completely abolished by excess nucleoside m2,2,7(3)G. The specificity of the antibody is further demonstrated by the complete absence of reaction with deproteinized snRNA species U6, the 5' terminus of which does not contain m2,2,7(3)G. Most importantly, the cap structures of the snRNAs U1a, U1b, U2, U4, and U5 are also accessible for anti-m2,2,7(3)G IgGs when intact snRNPs are reacted with the antibody. In this case, snRNP species U6 is coprecipitated, suggesting that there are intermolecular interactions between this and other snRNPs. Our data demonstrate that the 5'-terminal regions of the above snRNAs are not protected by the snRNP proteins. This finding is of special interest for snRNP species U1, and is discussed in terms of a model which proposes that the 5'-terminal region of U1 participates in the proper alignment of splice junctions in eucaryotic pre-mRNAs (Lerner, M. R., Boyle, J.A., Mount, S.M., Wolin, S.L., and Steitz, J. A. (1980) Nature (Lond.) 283, 220-224).


Buying Time: Medicine's Warnings Prompt CMS to Delay Dramatic Coding and Payment Changes.
Medicine's warnings prompt CMS to delay dramatic coding and payment changes.


Pharmacogenetic profile and major depressive and/or bipolar disorder treatment: a retrospective, cross-sectional study.
To compare pharmacogenetic test predictions with self-reported treatment experience and side effect tolerability among patients with depression taking psychotherapeutic medications. Subjects completed a survey recalling medication effectiveness and side effects and then underwent pharmacogenetic testing. Our 15 gene pharmacogenetic panel predicted efficacy (p < 0.001) but did not predict side effect tolerability (p = 0.70) in a group of 352 patients. The pharmacogenetic panel and reported efficacy corresponded 60% of the time and medication tolerability agreed 71% of the time. Pharmacogenetic testing may be a useful adjunct to predict efficacy of medications used to treat depression.


Author Correction: PTENα and PTENβ promote carcinogenesis through WDR5 and H3K4 trimethylation.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Coexistence and interference in two submersed freshwater perennial plants.
Interactions between two codominant submersed freshwater perennial plants, Eleocharis acicularis (L.) R. and S. and Juncus pelocarpus forma submersus Fassett, were studied in a softwater lake. Analysis of segregation indicated a nonrandon arrangement of individual rosettes of each species with respect to rosettes of the other species. Factors influencing growth of the species were examined using de Wit replacement series replicated four times at five ratios, under three environmental treatments: Sphagnum peat, double field density, and shading, and a control.Plants grown in pure culture showed no significant different in yield between the two species. When plants were grown in mixture, there were significant differences between species. Yields of both species were significantly different among environmental treatments. A significant effect of Eleocharis: Juncus ratio in the double density treatment resulted from interference among conspecific neighbors. Relative Yield Totals ranged from 0.84 to 1.0 for all four treatments, and ratio diagrams indicate stable coexistence through the growing season under all four environmental regimes. Interspecific interference was less important than environmental factors and intraspecific interference in determining growth in these experiments. Eleocharis and Juncus are nonrandomly intermingled, and can coexist under a variety of environmental manipulations. This outcome is consistent with their reported distributions in nature. The mechanism that permits this stable coexistence awaits explanation.


Cyclophosphamide potentiates the antitumor activity of v-p97NY.
Previous work has demonstrated that a recombinant live vaccinia virus-based tumor vaccine, v-p97NY, induces an immune response in mice which can lead to the rejection of transfected lines of mouse melanoma cells expressing the human melanoma antigen p97 (S.-L. Hu et al., J. Virol. 62, 176, 1988; C. D. Estin et al., Proc. Natl. Acad. Sci. USA 85, 1052, 1988). We now show that the ability of v-p97NY to induce delayed-type hypersensitivity to p97 improved if the vaccinated mice were given cyclophosphamide (Cy) on the day of vaccination. Likewise, treatment of vaccinated mice with Cy increased the antitumor activity of vaccination so that tumor colony formation in the lungs was inhibited even when v-p9NY plus Cy was not given until 7 days after intravenous injection of tumor cells.


Isolation of cardiac cells from E8.5 yolk sac by ALCAM (CD166) expression.
It is known that the adhesion molecule ALCAM (CD166) mediates metastasis of malignant cells and organogenesis in embryos. We show here that embryonic day 8.5 (E8.5) murine yolk sac cells express ALCAM protein and that ALCAM expression can be used to define endothelial and cardiac precursors from hematopoietic precursors in E8.5 yolk sacs. ALCAM high+ cells exclusively give rise to endothelial and cardiac cells in matrigel assays but generate no hematopoietic colonies in methylcellulose assays. ALCAM low+ and ALCAM- populations predominantly give rise to hematopoietic cells in methylcellulose, but do not generate any cell clusters in matrigel. The ALCAM high+ population contains both Flk-1+ and Flk-1- cells. The former population exclusively contains endothelial cells whereas the latter give rise to cardiac cells when cultured on OP9 stromal cells. We also show that cardiac lineage marker genes such as Nkx-2.5, and the endothelial marker VE-cadherin are expressed in the ALCAM high+ fraction, whereas the hematopoietic marker GATA1 and Runx1 are expressed in the ALCAM low+/- fraction. However, we did not detect expression of the cardiac structural protein cTn-T in cells from yolk sac cells until these had had been differentiated on OP9 for 5 days. Altogether, these results indicate that cells retaining a potential to differentiate to the cardiac lineage are present in E8.5 yolk sacs and can be isolated as ALCAM high+, Flk-1- cells. Our report provides novel insights into the origin and differentiation process of cardiac cells in the formation of the circulatory system.


Insulin and placenta: degradation and stabilization, binding to microvillous membrane receptors, and amino acid uptake.
Human placenta possesses insulin receptors, yet whether insulin affects uptake of substrate or other placental functions is still controversial. A potential problem in the study of this issue is degradation of insulin by placental tissue. We found insulin degradation to be rapid and temperature dependent. At 10 mU/ml and 37 degrees C, 40% became trichloroacetic acid soluble within 15 minutes. Degradation was decreased by preincubation of tissue, followed by change of medium and by addition of 0.5% to 2.0% bovine albumin. Receptor assay with isolated microvillous membrane, which bound insulin with the characteristics of known target tissues, demonstrated biologically active insulin (5 to 6 mU/ml) to persist under incubation conditions. The presence of insulin did not influence the uptake of amino acids by the three neutral amino acid transport systems of the human placenta. Thus the transport of an essential fetal nutrient is is apparently independent of fluctuations in maternal insulin with dietary carbohydrate intake and disease.


Selective alteration of erythrocyte deformabiliby by SH-reagents: evidence for an involvement of spectrin in membrane shear elasticity.
In order to elucidate the molecular basis of membrane shear elasticity, the effect of membrane protein modification by SH-reaents on the deformability of human erythrocytes was studied. Deformability was quuantified by measuring the elongation of erythrocytes subjected to viscometric flow in a transparent cone plate viscometer. Impermeable SH-reagents proved to have no mechanical effect. Many, but not all, permeable SH-reagents markedly decreased the elongation. Among these, bifunctional SH-reagents (e.g. diamide, tetrathionate and N, N' -p-phenylenedimaleimide) able to cross-link membrane SH-groups were more effective than monofunctional SH-reagents (e.g. N-ethylmaleimide and ethacrynic acid). The bifunctional SH-reagents produced a 50% decrease of elongation after modification of less than 5% of the membrane SH-groups. In contrast, for a comparable effect, more than 20% of the SH-groups had to be modified by the monofunctional reagents. The effect of SH-oxidizing agents was fully reversible after treatment with disulfide-reducing agents. All bifunctional SH-reagents induced a dimerization of a small fraction of spectrin. Anaalysis of the distribution of the diamide-induced disulfide bonds among the various membrane protein fractions showed that this agent preferentially acts on the spectrin polypeptides. The results provide direct experimental evidence that the native arrangement of spectrin is essential for the shear resistance of the erythrocyte membrane and that introduction of small numbers of intermolecular cross-links as well as modification within the molecule lead to a rapid loss of this function.


Hansen-Street nailing of fractures of the femoral shaft. A study of 70 consecutive cases.
A series is presented of 70 consecutive cases of fractures of the femoral shaft fixed with the solid Hansen-Street nail. They were followed until the nail was removed and the patient fully recovered. There were no deep infections, but one pseudarthrosis. There were four cases of fat embolism. The mean time spent in hospital was 32 days, and the patients began to take full weight at an average of 14 weeks after the injury. It was concluded that Hansen-Street nailing is a safe procedure which does not demand advanced technical skills or equipment.


Influence of light and neural circuitry on tyrosine hydroxylase phosphorylation in the rat retina.
Light has been shown to increase dopamine synthesis and release in vertebrate retinas, but the retinal circuits mediating the light signal are unknown. We utilized three antibodies which recognize phosphorylated forms of tyrosine hydroxylase (TH) at serines 19, 31, and 40 to study the effects of light and neuroactive drugs on TH phosphorylation in the rat retina. Phosphorylated TH and total TH immunoreactivities were co-localized exclusively in retinal neurons whose shape and location are characteristic of dopaminergic interplexiform cells. Phosphorylated TH was weak to absent in darkness, but light strongly stimulated phosphorylation in all the three serine residues. Light-induced phosphorylation of TH induction by light was uniformly blocked by a combination of NMDA and AMPA glutamate receptor antagonists. In darkness, the combination of NMDA+AMPA induced phosphosphorylation of TH at serines 19 and 40 but it was weak at serine 31. A GABA(A) antagonist had the same effect. An agonist of depolarizing (ON) bipolar cells, L-(+)-2-amino-4-phosphonobutyric acid, did not prevent light-induced phosphorylated TH formation. Carbachol, a non-specific cholinergic agonist, selectively induced phosphorylation of TH at serine 31 in darkness, an effect which was blocked by the nicotinic antagonist, d-tubocurarine. These results show that retinal circuits involving glutamatergic, GABAergic and cholinergic synapses influence phospho-TH formation at different serine residues in this enzyme. Gamma amino butyric acid (GABA) and glutamate influence TH phosphorylation at serines 19 and 40, whereas cholinergic inputs affect its phosphorylation at serine 31.


Studies on immunoreactive gastrin with special regard to its molecular form and G cell counts in gastrointestinal mucosa of fetal, neonatal and adult rats.
Changes of distribution of immunoreactive gastrin (IRG) and molecular forms of intra-tissue gastrin in the growth course of rats were examined. The results obtained were as follows; 1) IRG concentrations and G cell counts were extremely low in the fetal antral mucosa. However, a gradual increase of the above was observed during the neonatal suckling period, accompanied by a rapid increase at the commencement of feeding. 2) IRG concentrations in the duodenal mucosa of the fetal and neonatal period were markedly higher than that of adult rat. 3) Jejunal IRG concentration was negligible in the fetal period. The value obtained from the postnatal rats was equal to or higher than that of adult rat. 4) The major form of antral gastrin was G-17 throughout the fetal and adult age. No qualitative change of antral IRG in the growth course of rats was seen. 5) The major form of the duodeno-jejunal mucosa was G-17 in the fetal period and thereafter G-34 increased gradually in the growth course of rats. These results suggested that, (1) suckling and feeding appeared to be a trigger of the production and release of antral gastrin in the growth course of rats. (2) In the initial stage of the growth, G cells distributed in the duodeno-jejunal mucosa as well as in the antral mucosa may participated in the production and release mechanism of gastrin.


Diffuse hepatic uptake of technetium-99m methylene diphosphonate in a patient receiving high dose methotrexate.
A child with diffuse accumulation of [99mTc]MDP in the liver on a bone scan, at the time of study the patient had a severe, but reversible, hepatic dysfunction on the basis of methotrexate toxicity. Visualization of the liver on skeletal scintigrams can be a consequence of high-dose methotrexate therapy, as there was no other explanation for this unusual finding.


The comparative analysis of species occurrence patterns on archipelagos.
We present a technique based on recent developments in contingency table analysis to analyze species occurrence patterns on archipelagos. This technique, through a "logistic" transformation, fits a sigmoidal-shaped surface on the species presence-absence matrix using only three parameters. This technique does not follow from any a priori or theoretical motivation, but is simply a descriptive statistical procedure. It accounts for roughly half the variation of the empirical contingency matrices for 14 different island systems. The taxa studied included plants, birds, herps and mammals. The matrix technique for a set of species in an archipelago provides three biologically relevant summary statistics. The first statistic indicates the overall colonizing success of the species in the archipelago. The second statistic describes the orderedness of the matrix (species occurrences). The third indicates the distribution of colonizing success between species. The technique is useful in computing the range of these statistics across taxa and over archipelagos.


Coexistence of expressed and non-expressed alpha-fetoprotein genes in somatic cell hybrids.
Hybrids have been generated between mouse hepatoma cells, which actively synthesize alpha-fetoprotein (AFP), and adult hepatocytes, where AFP production is shut off. These hybrids maintain an active synthesis of mouse AFP. Using a specific radioimmunoassay, we found that rat AFP production is not activated. Southern blot analysis showed that mouse and rat AFP DNA sequences can be distinguished and that hybrid clones possessing something close to the complete chromosome sets of both parents have retained both parental AFP DNA sequences. Thus expressed and non-expressed AFP genes coexist in these hybrid cells as if their expression were dependent on a cis-acting event.


"Variances" and "in-variances" in hierarchical porosity and composition, across femoral tissues from cow, horse, ostrich, emu, pig, rabbit, and frog.
It is very well known that bone is a hierarchically organized material produced by bone cells residing in the fluid environments filling (larger) vascular pores and (smaller) lacunar pores. The extracellular space consists of hydroxyapatite crystals, collagen type I molecules, and water with non-collageneous organics. It is less known to which extent the associated quantities (mineral, organic, and water concentrations; vascular, lacunar, and extracellular porosities) vary across species, organs, and ages. We here investigate the aforementioned quantities across femoral shaft tissues from cow, horse, emu, frog, ostrich, pig, and rabbit; by means of light microscopy and dehydration-demineralization tests; thereby revealing interesting invariances: The extracellular volume fractions of organic matter turn out to be similar across all tested non-amphibian tissues; as do the extracellular volume fractions of hydroxyapatite across all tested mammals. Hence, the chemical composition of the femoral extracellular bone matrix is remarkably "invariant" across differently aged mammals; while the water content shows significant variations, as does the partitions of water between the different pore spaces. The latter exhibit strikingly varying morphologies as well. This finding adds to the ample "universal patterns" in the sense of evolutionary developmental biology; and it provides interesting design requirements for the development of novel biomimetic tissue engineering solutions.


Illustration of sexual differentiation to undergraduates with a conditional gene expression system.
This work describes the development and evaluation of a two-session laboratory class based on Tet-on technology and sex determination in the fruit fly Drosophila melanogaster. The Tet-on system allows conditional control of gene expression, when doxycycline is applied. A laboratory exercise has been developed to illustrate how the Tet-on technology conditionally over-expresses the key sex determining gene transformer (tra) during development and how to inhibit sex differentiation in males, results in a lack of external genitalia and sex comb size reduction. The laboratory practice is inexpensive and straightforward, while allowing students to understand well how molecular biology technology can change biological processes, including development. © 2018 by International Union of Biochemistry and Molecular Biology, 46(5):523-526, 2018.


Correlations between human salivary levels of lysozyme, lactoferrin, salivary peroxidase and secretory immunoglobulin A with different stimulatory states and over time.
Within-subject correlations for the levels of these salivary proteins were determined in unstimulated and stimulated parotid saliva collected from 8 subjects and for stimulated parotid saliva collected from the same subjects once a week for a 4-week period. Initial correlations between unstimulated and stimulated samples were high and statistically significant (p less than 0.05) for all four proteins. When data were adjusted for variation attributable to flow rate and total protein, some correlations remained the same and those for lysozyme, lactoferrin and salivary peroxidase increased. However, the correlation for secretory immunoglobulin A decreased to a point where it was no longer statistically significant. In the weekly comparison, within-subject correlations across weeks were significant (p less than or equal to 0.05) for lysozyme, lactoferrin and salivary peroxidase, but not for immunoglobulin A. After adjustment for flow rate and total protein, the pattern of correlation was unchanged. Thus the relative rankings of subjects for levels of lysozyme, lactoferrin or salivary peroxidase may be consistent across stimulatory states, even though absolute concentrations may change; levels of these proteins in stimulated parotid saliva may be maintained over time. Secretory immunoglobulin A appears to be more subject to short-term variation.


Evidence for constitutively-active adenosine receptors at mammalian motor nerve endings.
A study was made to determine if constitutively active adenosine receptors are present at mouse motor nerve endings. In preparations blocked by low Ca(2+)/high Mg(2+) solution, 8-cyclopentyl-1,3,dipropylxanthine (CPX, 10-100 nM), which has been reported to be both an A(1) adenosine receptor antagonist and inverse agonist, produced a dose-dependent increase in the number of acetylcholine quanta released by a nerve impulse. Adenosine deaminase, which degrades ambient adenosine into its inactive congener, inosine, failed to alter the response to 100 nM CPX. 8-Cyclopentyltheophylline (CPT, 3 μM), a competitive inhibitor at A(1) adenosine receptors, prevented the increase in acetylcholine release produced by CPX. At normal levels of acetylcholine release, neither adenosine deaminase nor CPX affected acetylcholine release at low frequencies of nerve stimulation in (+)-tubocurarine blocked preparations. The results suggest that a proportion of the acetylcholine release process is controlled by constitutively active adenosine receptors at murine motor nerve endings, providing the first evidence for constitutive activity of G-protein-coupled receptors that modulate the function of mammalian nerve endings.


Serum Growth Differentiation Factor 15 Levels Are Associated With Depression After Ischemic Stroke.
Background The effect of serum growth differentiation factor 15 (GDF-15) on poststroke depression (PSD) remains unknown. This study aimed to investigate the association between serum GDF-15 and PSD among patients with ischemic stroke. Methods and Results This study was based on a random sample from CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). A total of 572 patients from 7 participating hospitals with GDF-15 levels were included in this analysis. The study outcome was depression (Hamilton Depression Rating Scale score ≥8) at 3 months after ischemic stroke. A total of 231 (40.4%) patients with stroke experienced PSD within 3 months. The multivariate-adjusted odds ratio of PSD associated with the highest tertile of serum GDF-15 was 2.92 (95% CI, 1.36-6.27) compared with the lowest tertile. Each SD increase in log-transformed GDF-15 was associated with a 42% (95% CI, 2%-97%) increased risk of PSD, and a linear association between serum GDF-15 and the risk of PSD was observed (P for linearity=0.006). Conclusions Elevated serum GDF-15 levels in the acute phase of ischemic stroke were independently associated with PSD, suggesting that GDF-15 may be a valuable prognostic biomarker for PSD.


Comparison of labour and birth outcomes between nulliparous women who used epidural analgesia in labour and those who did not: A prospective cohort study.
To compare labour and birth outcomes between nulliparous women who used versus did not use intrapartum epidural analgesia. Prospective cohort study. Two maternity hospitals in Ireland. A total of 1221 nulliparous women who gave birth vaginally or by emergency caesarean section. Multinomial logistic regression was used to analyse categorical outcomes, with results presented as ratios of relative risks (RRR). For dichotomous outcomes we used logistic regression, with results presented as odds ratios (OR). Mode of birth, IV syntocinon use, pyrexia (≥38°C), antibiotic treatment, first stage labour ≥10h, second stage labour ≥2h, blood loss (≥500mls, ≥1000mls), perineal trauma. Neonatal outcomes included Apgar score ≥7 at 1min and 5min, admission to neonatal intensive care unit, and infant feeding method. Women using EA were more likely to require a vacuum-assisted birth (RRR 3.35, p<0.01) or forceps-assisted birth (RRR 11.69, p<0.01). Exposure to EA was associated with significantly greater risk of ≥10h first (OR 6.72, p=0.01) and ≥2h second (OR 2.25, p<0.01) stage labour, increased likelihood of receiving IV syntocinon (OR 9.38, p<0.01), antibiotics (OR 2.97, p<0.01) and a greater probability of pyrexia (OR 10.26, p<0.01). Women who used EA were half as likely to be breastfeeding at three months postpartum (OR 0.53, p<0.01). No differences were observed between groups in neonatal outcomes. Our data shows significant associations between EA use and several intrapartum outcomes.


Rates of Intimate Partner Violence Perpetration and Victimization Among Adults With ADHD.
Research has demonstrated an association between ADHD and intimate partner violence (IPV). However, it is unclear whether adults with ADHD persisting from childhood are especially at risk, and whether ADHD is a unique risk factor beyond well-established predictors of IPV. Adults with ( n = 95) and without childhood histories of ADHD ( n = 121) who were recruited from Amazon's Mechanical Turk reported their levels of IPV perpetration and victimization, and provided data on additional risk factors of IPV (e.g., childhood maltreatment, alcohol abuse). While controlling for additional risk factors, adults diagnosed with ADHD as children, particularly those with elevated current ADHD symptoms (ADHD-Persist), reported higher rates of IPV perpetration and victimization than adults with ADHD histories but low current symptoms (ADHD-Desist) and adults who were never diagnosed with ADHD (control). Adults with ADHD histories and elevated current symptoms are most likely to report IPV perpetration and victimization.


Does water flow type influence performances of reed based constructed wetland for wastewater treatment?
The application of Phragmites australis based constructed wetlands (CW) have been widely used in various climates and also used for secondary treatment of diverse wastewater and polluted water. This work compares the treatment performance of two Phragmites-based mesocosms: the first with surface horizontal flow (SF), and the other with subsurface horizontal flow (SSF), in the same conditions of feeding and climate. The results showed a significantly high mineral content of the effluent water exiting SSF-CW. The last one was significantly more efficient in terms of removal of Total Suspended Solids (TSS), Chemical Oxygen Demand (COD), Total Nitrogen (TN), ammonium (NH4-N), and Total Phosphorus (TP) compared to SF-CW, i.e. 26.3, 3.12, 1.59, and 0.62 g. m-2. day-1 in the same order. The microbiological load reduction is also significantly higher in SSF-CW. On the contrary, the other parameters of pollution monitored do not allow the identification of a significant difference between SF- and SSF-CW. The atmospheric evapotranspiration value was higher in SSF-CW by 24.8 ± 20 mm. d-1, corresponding also to a higher harvestable biomass of Phragmites of 58.2 t. ha-1. year-1.


Mammographic changes after hormone replacement therapy in patients who have undergone breast irradiation.
We examined three patients who began hormone replacement therapy after lumpectomy and breast irradiation. In these women increased tissue density appeared on mammography only or disproportionately in the nonirradiated breast. To our knowledge, this observation has not been reported. Breast irradiation may induce tissue changes that prevent or diminish the proliferative response that can be induced in breast tissue by postmenopausal hormone replacement therapy. Because this treatment is now recommended for some women after breast conservation therapy, mammographers may recognize this finding with increasing frequency.


Housing conditions alter GABAA receptor of alcohol-preferring and -nonpreferring rats.
The effects of housing conditions on some functional properties of the GABAA benzodiazepine (BZD) receptor in the cerebral cortex were examined in the selectively bred alcohol-preferring (P) and -nonpreferring (NP) lines of rats. Compared to rats housed in pairs (P with P and NP with NP), P and NP rats housed individually had 44% (p < 0.005) and 32% (p < 0.01) lower values, respectively, for GABA-stimulated 36Cl- influx into cortical microsacs. The maximal effect (Vmax) of flunitrazepam (FNZ) to enhance GABA-stimulated 36Cl- uptake was 44% higher in individually housed P rats than pair-housed P rats (p < 0.05) and 51% higher than individually housed NP rats (p < 0.05). There was no difference between single and pair-housed NP rats for Vmax values of FNZ enhancement of GABA-stimulated 36Cl- influx. The results show housing conditions can alter some of the functional properties of the GABAA/BZD receptor in the P and NP lines of rats. The differential effect of housing conditions on FNZ enhancement of 36Cl- influx, observed between the lines, may be a result of higher levels of anxiety being produced by brief isolation in the P rat.


Arthroscopic treatment of lateral epicondylitis: indication, technique and early results.
The purpose of this study is to present the results of the arthroscopic treatment of lateral epicondylitis. Twenty patients with lateral epicondylitis (mean age 42 years) were treated arthroscopically. The average duration of symptoms prior to surgery was 14 months. The arthroscopic joint inspection showed an intact capsule in seven patients (type-I lesion), in eight patients a linear capsule tear (type-II lesion) and in six patients a complete rupture of the capsule (type-III lesion). An associated intraarticular pathology was documented in eight patients. Within an average follow-up period of 1.8 years, local pain and function were documented and analyzed. Subjective pain at rest was reduced from 5.0 to 0.5 points, pain at daily living activities from 6.0 to 1.0 points and pain at athletic activities from 7.3 to 1.2 points in the VAS score. Function increased from 5.2 to an average value of 10.9 (max. 12 points). Patients returned back to work after 3.2 weeks. In conclusion, the arthroscopic release in patients with radial epicondylitis is a reproducible method with a marked postoperative increase in function within a short rehabilitation period.


A comprehensive analysis of trends and determinants of HIV/AIDS knowledge among the Bangladeshi women based on Bangladesh Demographic and Health Surveys, 2007-2014.
South-Asian countries are considered to be a potential breeding ground for HIV epidemic. Although the prevalence of this incurable disease is low in Bangladesh, women still have been identified as more vulnerable group. The aim of this study is to assess the knowledge about HIV/AIDS: its trends and associated factors among the women in Bangladesh. We analysed the nationally representative repeatedly cross-sectional Bangladesh Demographic and Health Surveys (BDHSs) data: 2007, 2011, and 2014. These data were clustered in nature due to the sampling design and the generalized mixed effects model is appropriate to examine the association between the outcome and the explanatory variables by adjusting for the cluster effect. Overall, women's knowledge about HIV/AIDS has been decreasing over the years. Education plays the leading role and secondary-higher educated women are 6.6 times more likely to have HIV/AIDS knowledge. The likelihood of knowledge is higher among the women who had media exposure (OR: 1.6) and knowledge on family planning (OR: 2.3). A rural-urban gap is noticed in women's knowledge about HIV/AIDS and significant improvement has been observed among the rural and media exposed women. Results reveal that age, region, religion, socio-economic status, education, contraceptive use have significant (p<0.01) effects on women's knowledge about HIV/AIDS. This study recommends to emphasis more on women's education, media exposure, and family planning knowledge in strengthening women's knowledge about HIV/AIDS. In addition, residence specific programs regarding HIV/AIDS awareness also need to be prioritized.