Superior accuracy of mid-regional proadrenomedullin for mortality prediction in sepsis with varying levels of illness severity.
The use of novel sepsis biomarkers has increased in recent years. However, their prognostic value with respect to illness severity has not been explored. In this work, we examined the ability of mid-regional proadrenomedullin (MR-proADM) in predicting mortality in sepsis patients with different degrees of organ failure, compared to that of procalcitonin, C-reactive protein and lactate. This was a two-centre prospective observational cohort, enrolling severe sepsis or septic shock patients admitted to the ICU. Plasma biomarkers were measured during the first 12 h of admission. The association between biomarkers and 28-day mortality was assessed by Cox regression analysis and Kaplan-Meier curves. Patients were divided into three groups as evaluated by the Sequential Organ Failure Assessment (SOFA) score. The accuracy of the biomarkers for mortality was determined by area under the receiver operating characteristic curve (AUROC) analysis. A total of 326 patients with severe sepsis (21.7%) or septic shock (79.3%) were enrolled with a 28-day mortality rate of 31.0%. Only MR-proADM and lactate were associated with mortality in the multivariate analysis: hazard ratio 8.5 versus 3.4 (p < 0.001). MR-proADM showed the best AUROC for mortality prediction at 28 days in the analysis over the entire cohort (AUROC [95% CI] 0.79 [0.74-0.84]) (p < 0.001). When patients were stratified by the degree of organ failure, MR-proADM was the only biomarker to predict mortality in all severity groups (SOFA ≤ 6, SOFA = 7-12, and SOFA ≥ 13), AUROC [95% CI] of 0.75 [0.61-0.88], 0.74 [0.66-0.83] and 0.73 [0.59-0.86], respectively (p < 0.05). All patients with MR-proADM concentrations ≤0.88 nmol/L survived up to 28 days. In patients with SOFA ≤ 6, the addition of MR-proADM to the SOFA score increased the ability of SOFA to identify non-survivors, AUROC [95% CI] 0.70 [0.58-0.82] and 0.77 [0.66-0.88], respectively (p < 0.05 for both). The performance of prognostic biomarkers in sepsis is highly influenced by disease severity. MR-proADM accuracy to predict mortality is not affected by the degree of organ failure. Thus, it is a good candidate in the early identification of sepsis patients with moderate disease severity but at risk of mortality.


How we developed, at the Centre/Institute for Neuromuscular Diseases, differential diagnostics of Spinal Muscle Atrophies / Amyotrophic Lateral Sclerosis (SMA/ALS) and tried to influence the development of the disease.
In our research, we placed the emphasis on delimiting fatal diseases against those that have some similar symptoms, but can be improved, even completely cured. More often we succeeded in differentiating the local compressive factor. In our search for early symptoms, we also found physiological, although quite unusual EMG phenomena. High amplitude neural potentials confirmed the malignant disease diagnosis. The spinal angiography discovered arterial pathology, while CT demonstrated localised hydromyelia. Amyotrophic syndromes caused by chronic led intoxications represented a separate group. Patients would recover significantly on d-penicillamine. We applied it successfully in amyotrophic syndromes with laboratory confirmed copper metabolism disorders. A very significant therapeutic effect was obtained in a patient with SMA without similar laboratory, even in recidivism. Exceptionally, we were able to achieve significant remission with corticosteroids, too. The remaining patients, differentiated as certainly fatal, represented a separate group. We tried to elaborate the special psychosocial and ethical problems connected with its outcome in "round table discussions". The first one was in 1989, at the workshop with King Engel, and the second in 1990, on the Fourth Yugoslav Symposium on Neuromuscular Diseases. In 1990, I visited Cicely Saunders and the St. Christopher's hospice in London, and in 1994 I started to organised hospice movement in Croatia.


Pain on injection: a double-blind comparison of propofol with lidocaine pretreatment versus propofol formulated with long- and medium-chain triglycerides.
The incidence of pain on injection of propofol has been reported to be 70%. A new propofol formulation with a 10% emulsion of long- and medium-chain triglycerides (LCT/MCT) is associated with less pain on injection. Our goal was to compare the effect of propofol-LCT/MCT on the incidence of pain versus propofol with lidocaine 40 mg IV pretreatment injected as a Bier's block. Two hundred healthy women scheduled for ambulatory gynecological procedures were allocated to 1 of 2 groups in a randomized double-blind fashion. Group LIDO received lidocaine 2% 2 mL injected with a tourniquet 1 min before propofol 1% 2 mg/kg IV; group LCT/MCT received NaCl 0.9% 2 mL with tourniquet 1 min before propofol-LCT/MCT 1% 2 mg/kg IV. Spontaneous verbal expressions of pain, movement of hand, frowning, and moaning during the injection were recorded. The incidence and severity of pain were assessed 30 min and 6 h after surgery. Recall of pain was considered with a visual analog scale (VAS) score >1, and pain was graded as VAS 0-10. More women reported spontaneous verbal expression of pain with propofol-LCT/MCT (47% versus 24%; P = 0.0014; relative risk 1.61 [95% confidence interval, 1.22-2.13]). Among women with a painful injection, there was no difference after surgery regarding the intensity of pain or recall of pain. In contrast to previous reports, we found that propofol-LCT/MCT resulted in a more frequent incidence of pain than propofol 1% with IV lidocaine pretreatment. This may be due to the diversity of pain definitions used in studies or to the lack of premedication in our study.


Positive inotropic and electrophysiological effects of APP 201-533 can be explained by an increase of cardiac cyclic AMP.
The possible mechanism of action of the positive inotropic agent APP 201-533 [3-amino-6-methyl-5-phenyl-2(1H)-pyridinone] was investigated. In guinea pig papillary muscles, APP 201-533 increased force of contraction concentration dependently at 10(-4)-10(-3) M. The effect was associated with an abbreviation of contraction and relaxation time. In guinea pig papillary muscles partially depolarized with 22 mM K+, APP 201-533 in concentrations of 10(-4) and 10(-5) M restored slow action potentials, which were not influenced by cimetidine, propranolol, and prazosin but were blocked by the Ca2+ antagonist PY 108-068 and by carbachol in an atropine-sensitive manner. The concentration-effect curve of histamine was shifted to the left in the presence of APP 201-533. These actions can be explained by the increase in cardiac cyclic AMP level that was found in rabbit papillary muscles and guinea pig left atria treated with APP 201-533 due to the known phosphodiesterase inhibitory effect of pyridinones. APP 201-533 increased the inotropic potency of dihydroouabain in guinea pig papillary muscles. It seems possible that this effect is based on an increased Ca2+ sensitivity of myocardial contractile structures as described previously for APP 201-533.


Should routine screening by mammography be replaced by a more selective service of risk assessment/risk management?
The NHS screening program was launched 20 years ago and, until recently, has been accepted in an uncritical way. However, emerging data have suggested that the reduction in breast cancer mortality owing to screening is much less than it has been credited for. Furthermore, the harms from false-positive results and the overdiagnosis of indolent disease, which includes the detection of a cancer that is not destined to present clinically in that patient's lifetime, are now perceived as much greater than ever anticipated. This article suggests that it is complacent to continue with the program unchecked, a program that has so far denied women an informed choice. It is also suggested that a more efficient use of scarce resources that may reduce all-cause mortality might be to shift from a 'one size fits all' approach, to a risk assessment/risk management scheme.


The Hegemonic Politics of 'Strategic Autonomy' and 'Resilience': COVID-19 and the Dislocation of EU Trade Policy.
The outbreak of COVID-19 in March 2020 led to substantial upheaval in the EU's trade policy. Over the course of a year, EU Trade Policy as a field witnessed the launch of hitherto unthinkable ideas; the proliferation of a range of new buzzwords such as resilience, autonomy, and reshoring; and ultimately the arrival of a new consensus in the Trade Policy Review of February 2021. This article uses a discourse-theoretical approach (PDT) to retrace the political process that unfolded throughout this year, from the start of the COVID-19 crisis, to a fundamental dislocation of EU trade politics, and ultimately to the consolidation of a partial, temporary, and frail new hegemony within the policy field. Our goal is to explain the trajectory and the dynamics of this process by studying the discourses, the framings, and the political strategies that comprised the hegemonic struggle underlying it.


Donor-state-enabling Er-related luminescence in silicon: direct identification and resonant excitation.
We conclusively establish a direct link between formation of an Er-related donor gap state and the 1.5 microm emission of Er in Si. The experiment is performed on Si/Si:Er nanolayers where a single type of Er optical center dominates. We show that the Er emission can be resonantly induced by direct pumping into the bound exciton state of the identified donor. Using two-color spectroscopy with a free-electron laser we determine the ionization energy of the donor-state-enabling Er excitation as E(D) approximately 218 meV. We demonstrate quenching of the Er-related emission upon ionization of the donor.


[Anhedonia in mood disorders and somatic diseases: results of exploratory Mendelian randomization analysis].
To conduct an exploratory Mendelian randomization analysis of the causal relationships of anhedonia with a wide range of psychiatric and somatic phenotypes based on the genetic data of participants in a population study. This cross-sectional study included 4520 participants, of which 50.4% (n=2280) were female. The mean age was 36.8 (S.D.=9.8) years. Participants were pheno-nailed based on the DSM-5 criteria for anhedonia in the framework of depression. An episode of anhedonia exceeding 2 weeks during life was reported by 57.6% (n=2604) of participants. A genome-wide association study (GWAS) of the anhedonia phenotype was performed, as well as a Mendelian randomization analysis using summary statistics of large-scale GWASs on psychiatric and somatic phenotypes. The GWAS on anhedonia did not reveal the variants with genome-wide significant association (p<10-8). The most significant (p=9.71×10-7) was the variant rs296009 (chr5:168513184) in an intron of the slit guidance ligand 3 (SLIT3) gene. Using Mendelian randomization, nominally significant (p<0.05) causal associations of anhedonia with 24 phenotypes were identified, which can be divided into 5 main groups: psychiatric/neurological diseases, inflammatory diseases of the digestive system, respiratory diseases, oncological diseases and metabolic disorders. The most significant causal effects of anhedonia were found for breast cancer (p=0.0004, OR=0.9986, 95% confidence interval (CI) (0.9978-0.999)), minimal depression phenotype (p=0.009, OR=1.004, 95% CI (1.001-1.007)), as well as for apolipoprotein A (p=0.01, OR=0.973, 95% CI (0.952-0.993)) and respiratory diseases (p=0.01, OR=0.9988, 95% CI (0.9980-0.9997)). The polygenic nature of anhedonia may cause the risks of comorbidity of this phenotype with a wide range of somatic diseases, as well as may be associated with mood disorders.


Acute vision loss after general anesthesia in a cat.
A 6-year-old, male castrated, domestic shorthair cat presented with a 2-week history of blindness following general anesthesia. Behavioral changes, lethargy, inappetence and neurological deficits were also noted. Ophthalmic evaluation revealed blindness, normal pupillary light response and dazzle response, but no other abnormalities. Serodiagnostic testing for common infectious agents was negative and a cerebrospinal fluid analysis was normal. History and postmortem examination following euthanasia revealed cerebrocortical necrosis most consistent with anesthesia related hypoxia.


Serum glycated albumin, but not glycated haemoglobin, is low in relation to glycemia in hyperuricemic men.
Measurements of glycated albumin (GA) as well as glycated haemoglobin (HbA(1C)) have been applied in order to monitor chronic glycemic control in diabetic patients. Since the levels of both glycated proteins are influenced by various factors other than glycemia, cautions are necessary to evaluate such measures in some specific conditions. In this study, we examined the effects of serum uric acid (UA) levels on these glycemic markers. One hundred and ninety-three men with normal glucose tolerance were enrolled in this study. Association of serum UA with BMI, plasma glucose (PG), high sensitivity CRP (hs-CRP), serum GA and HbA(1C) was analysed. Serum UA showed a significant positive correlation with BMI (R = 0.329, P < 0.0001) and hs-CRP (R = 0.306, P < 0.0001). Multivariate analysis revealed serum UA to be a significant positive explanatory variable for hs-CRP. There was a significant positive correlation of serum UA with the 2-h PG after 75 g OGTT but not fasting PG. Although there was no correlation of serum UA with HbA(1C), serum UA showed a significant inverse correlation with both serum GA (R = -0.402, P < 0.0001) as well as BMI-adjusted serum GA (R = -0.327, P < 0.0001). By multivariate analysis, serum UA was an explanatory variable for serum GA. Serum GA, but not HbA(1C), is set lower in relation to plasma glucose levels in hyperglycemic men. This may be caused by microinflammation associated with hyperuricemic state.


Body shape as a visual feature: Evidence from spatially-global attentional modulation in human visual cortex.
Feature-based attention modulates visual processing beyond the focus of spatial attention. Previous work has reported such spatially-global effects for low-level features such as color and orientation, as well as for faces. Here, using fMRI, we provide evidence for spatially-global attentional modulation for human bodies. Participants were cued to search for one of six object categories in two vertically-aligned images. Two additional, horizontally-aligned, images were simultaneously presented but were never task-relevant across three experimental sessions. Analyses time-locked to the objects presented in these task-irrelevant images revealed that responses evoked by body silhouettes were modulated by the participants' top-down attentional set, becoming more body-selective when participants searched for bodies in the task-relevant images. These effects were observed both in univariate analyses of the body-selective cortex and in multivariate analyses of the object-selective visual cortex. Additional analyses showed that this modulation reflected response gain rather than a bias induced by the cues, and that it reflected enhancement of body responses rather than suppression of non-body responses. These findings provide evidence for a spatially-global attention mechanism for body shapes, supporting the rapid and parallel detection of conspecifics in our environment.


Hematoxylin and eosin staining for detecting biofilms: practical and cost-effective methods for predicting worse outcomes after endoscopic sinus surgery.
Although biofilms have been implicated in poor prognosis after endoscopic sinus surgery (ESS), traditional methods detecting biofilm such as scanning electron microscope and confocal scanning laser microscope were rarely used in the practice. The aims of this study was to determine whether the presence or absence of a biofilm detected by hematoxylin and eosin (H&E) staining followed by light microscopy (LM) that is widely used in daily practice, predicts surgical outcomes after ESS. Retrospective analysis of prospectively collected data. Fifty-five consecutive adult patients (>18 years) who underwent ESS for chronic rhinosinusitis with a minimum of 12-months of follow-up were enrolled in this study. Random sinonasal mucosal samples were assessed for biofilm presence using H&E staining with LM. Three independent observers scored whether a biofilm was present or absent based on H&E staining/LM, and the interrater variability was calculated. Pre- and postoperative sinus symptoms and sinonasal mucosal grading were assessed. Biofilms were present in 28 patients (51%), and the intraclass correlation coefficient according to H&E staining/LM was 0.731. The presence of a biofilm was associated with a higher preoperative Lund-MacKay computed tomography score (22.3 for biofilm-positive patients vs. 18.6 for biofilm-negative patients; P=0.021) and persistent inflammation (mucosal edema and discharge) after ESS (P<0.05). The presence or absence of a biofilm based on H&E staining/LM is correlated with disease severity and surgical outcomes after ESS. H&E staining/LM for detecting biofilm could be practical and cost-effective methods for predicting prognosis of ESS.


Calculating slow-motional electron paramagnetic resonance spectra from molecular dynamics using a diffusion operator approach.
A number of groups have utilized molecular dynamics (MD) to calculate slow-motional electron paramagnetic resonance (EPR) spectra of spin labels attached to biomolecules. Nearly all such calculations have been based on some variant of the trajectory method introduced by Robinson, Slutsky and Auteri (J. Chem. Phys. 1992,96, 2609-2616). Here we present an alternative approach that is specifically adapted to the diffusion operator-based stochastic Liouville equation (SLE) formalism that is also widely used to calculate slow-motional EPR line shapes. Specifically, the method utilizes MD trajectories to derive diffusion parameters such as the rotational diffusion tensor, diffusion tilt angles, and expansion coefficients of the orienting potential, which are then used as direct inputs to the SLE line shape program. This approach leads to a considerable improvement in computational efficiency over trajectory-based methods, particularly for high frequency, high field EPR. It also provides a basis for deconvoluting the effects of local spin label motion and overall motion of the labeled molecule or domain: once the local motion has been characterized by this approach, the label diffusion parameters may be used in conjunction with line shape analysis at lower EPR frequencies to characterize global motions. The method is validated by comparison of the MD predicted line shapes to experimental high frequency (250 GHz) EPR spectra.


Hb E/Hb LeporeHollandia in a family from Bangladesh.
We describe a family from Bangladesh in which three children are compound heterozygotes for Hb E (alpha 2 beta 2, beta 26Glu Lys) and Hb Lepore (delta-beta fusion gene). PCR amplification and direct nucleotide sequencing established that the fusion gene is Hb LeporeHollandia, with the cross-over localized to a 40 bp window between codon 22 and IVS-1 nt 16 of the delta- and beta-globin genes. This unusual combination of mutations is associated with a relatively mild clinical phenotype, with all three affected siblings having microcytic anemia of moderate severity without the need for transfusions.


Effectively Predicting the Presence of Coronary Heart Disease Using Machine Learning Classifiers.
Coronary heart disease is one of the major causes of deaths around the globe. Predicating a heart disease is one of the most challenging tasks in the field of clinical data analysis. Machine learning (ML) is useful in diagnostic assistance in terms of decision making and prediction on the basis of the data produced by healthcare sector globally. We have also perceived ML techniques employed in the medical field of disease prediction. In this regard, numerous research studies have been shown on heart disease prediction using an ML classifier. In this paper, we used eleven ML classifiers to identify key features, which improved the predictability of heart disease. To introduce the prediction model, various feature combinations and well-known classification algorithms were used. We achieved 95% accuracy with gradient boosted trees and multilayer perceptron in the heart disease prediction model. The Random Forest gives a better performance level in heart disease prediction, with an accuracy level of 96%.


Proenkephalin gene expression in the primate uterus: regulation by estradiol in the endometrium.
Proenkephalin mRNA has previously been shown to be expressed in the rodent uterus with varying levels during the estrous cycle. To examine for the potential regulation of proenkephalin gene expression by steroid hormones in a primate displaying a menstrual cycle and to define the functional tissue within the uterus expressing this transcript, we have used Northern blot analysis of extracted RNA from isolated uterine tissue subtypes from normal adult rhesus macaques obtained during the menstrual cycle and from ovariectomized females under different physiological steroid hormone treatments. A strong band of proenkephalin mRNA of 1.3 kilobases was detected almost exclusively in the proliferative endometrium from monkeys in the follicular phase of the cycle. No proenkephalin mRNA was detected in secretory endometrium obtained from monkeys in the luteal phase. When ovariectomized macaques were implanted with silastic capsules of 17 beta-estradiol, proenkephalin mRNA was detected in the endometrium but not the myometrium of the estradiol-treated animals. No proenkephalin mRNA was detected in ovariectomized control animals. Under these conditions, we were unable to detect proenkephalin mRNA in ovariectomized macaques implanted with separate silastic capsules of 17 beta-estradiol and progesterone or in decidual tissue from early or late pregnancy. These results suggest that in the primate uterus 1) proenkephalin mRNA is expressed primarily in the endometrium of the uterus, 2) expression of the proenkephalin gene is regulated by 17 beta-estradiol in the endometrium, and 3) this effect of estradiol is antagonized by progesterone.


Therapeutic use of cannabis: Prevalence and characteristics among adults in Ontario, Canada.
To investigate the prevalence of therapeutic cannabis use within a general population sample of adults and to describe various characteristics associated with use. Data were derived from the 2013 and 2014 CAMH Monitor Survey of adults in Ontario, Canada. This repeated cross-sectional survey employed a regionally stratified design and utilized computer-assisted telephone interviewing. Analyses were based on 401 respondents who reported using cannabis. The data indicated that 28.8% of those who used cannabis in the past year self-reported using cannabis for therapeutic purposes. Of therapeutic users, 15.2% reported having medical approval to use cannabis for therapeutic purposes. Cannabis use for therapeutic purposes was associated with more frequent use of cannabis, a moderate to high risk of problematic cannabis use, and a greater likelihood of using prescription opioids for medical purposes. There was little difference in cannabis use for therapeutic purposes according to sex, age, and marital status after adjusting for opioid use and problematic cannabis use. Findings suggest some potential negative consequences of cannabis use for therapeutic purposes; however, further research is needed to better understand the range and patterns of use and their corresponding vulnerabilities.


EPR emergency dosimetry with plastic components of personal goods.
Radiation-induced electron paramagnetic resonance (EPR) signals were studied in samples of plastic materials of various origin: buttons, details of underwear, elements of mobile phones, etc. The following parameters were investigated: dose response curve in the range 0-25 Gy; stability of potential dosimetric signals at different temperatures of storage after exposure; and influence of solar radiation on the dosimetric properties of materials. Plastics from personal goods were found to be a potentially acceptable material for use as individual EPR dosimeters with sensitivity threshold below 5 Gy. Radiation-induced EPR signals in plastic demonstrated clear saturation for doses above 10 Gy. Fading of dosimetric signals was best described by the two-exponential decay function with fast and slow decay components. Values of slow decay constant were approximately 2 and 15 d, while the corresponding values for the fast decay component were approximately 2 and 15 h for temperatures of +25 degrees C and -18 degrees C, respectively. Strong influence of solar light radiation on EPR spectra was observed for unexposed and gamma-irradiated plastic samples, which may affect drastically the results of dose reconstruction.


First results of the application of isozyme analysis to study of Culicoides (Diptera: Ceratopogonidae).
Results of a biochemical study on the genus Culicoides are reported. A method of analysis using six discriminant enzymatic systems was used and the results obtained on zymograms are detailed. A genetic study of C. nubeculosus, based on phosphoglucomutase was carried out. The processing of the data obtained, by means of correspondence analysis, provides an interesting comparative study between morphologically related species.


Infliximab in the treatment of tislelizumab-induced steroid-refractory immune checkpoint inhibitor-related pneumonia: case report and literature review.
Infliximab has been recommended by the American Society of Clinical Oncology (ASCO) guidelines for the treatment of steroid-refractory immune checkpoint inhibitor-related pneumonia (CIP), but clinical evidence remains insufficient. In order to improve the level of diagnosis and treatment and rational use of infliximab in the treatment of CIP, a successful case is reported and the relevant literature is reviewed. We report a 67-year-old male patient with small cell lung cancer (SCLC) who was admitted to hospital with rapidly worsening dyspnea and bilateral interstitial lung following PD-1 inhibitor (tislelizumab) combined with chemotherapy and radiation therapy. According to the comprehensive judgment of the patient's medical history, clinical symptoms, imaging manifestations, laboratory tests, exclusion of infection, heart failure and treatment response, the diagnosis of grade 4 CIP was made. The patient's condition did not improve after high-dose glucocorticoid and immunoglobulin therapy. After infliximab was added, the clinical manifestations and imaging were significantly improved, oxygenation index also gradually return to normal, then the patient was discharged smoothly. This report suggests that infliximab should be considered when high-dose glucocorticoids combined with immunoglobulin are ineffective for severe CIP. At the same time, this case indicates that inflammatory factors, especially tumor necrosis factor (TNF-α), may be prospective in predicting the efficacy of infliximab in the treatment of steroid-refractory CIP.


Risk allele of gene variant rs6584389 is associated with increased intima-media thickness in patients with type 2 diabetes.
Genome-wide association studies identified several gene variants associated with peripheral arterial disease (PAD). Among them, rs6584389 A>C was significantly associated with PAD defined by decreased ankle-brachial index (ABI). The aim of this study was to investigate whether the rs6584389 variant is also associated with the earlier stages of atherosclerosis assessed by intima-media thickness (IMT) or pulse-wave velocity (PWV) in clinically asymptomatic subjects with type 2 diabetes (T2DM), a group of patients with a high cardiovascular risk. In total, 111 patients with T2DM (56 females, 55 males) with a mean age 63.0 ± 9.1 years were consecutively included in the study. IMT was measured by ultrasound using 7 MHz linear transducer. PWV was measured using a piezoelectric method. Genotyping for rs6584389 was performed by PCR-HRMA method. The carriers of the risk C-allele of rs6584389 variant had significantly higher mean left-side IMT (AA: 0.67 ± 0.12, AC 0.77 ± 0.21, CC 0.78 ± 0.22 mm; p = 0.04). In multiple linear regression analysis, rs6586389 genotype was significantly associated with all measured IMT parameters. The presence of each risk C-allele predicted an increase in left-side IMT by 0.056 mm (p = 0.017), right-side IMT by 0.053 mm (p = 0.039), average IMT by 0.054 mm (p = 0.023), and maximal IMT by 0.058 mm (p = 0.021). Age and HbA1c levels were also significantly associated with increased IMT in all multivariate models. Gene variant rs6584389 A>C near to PAX2 gene was associated with increased carotid IMT in patients with type 2 diabetes independently of the other main risk factors for atherosclerosis.


Molecular structures of a series of substituted bis(η5-cyclopentadienyl)titanium dihalides CpR2TiX2 [X = F, Cl, Br and I; R = CHPh2, CH(p-Tol)2 and adamantyl].
Metallocene dihalides and derivatives thereof are of great interest as precursors for catalysts in polymerization reactions, as antitumor agents and, due to their increased stability, as suitable starting materials in salt metathesis reactions and the generation of metallocene fragments. We report the synthesis and structural characterization of a series of eleven substituted bis(η5-cyclopentadienyl)titanium dihalides, namely bis[η5-1-(diphenylmethyl)cyclopentadienyl]difluoridotitanium(IV), [Ti(C18H15)2F2], bis{η5-1-[bis(4-methylphenyl)methyl]cyclopentadienyl}difluoridotitanium(IV), [Ti(C20H19)2F2], and bis{η5-1-[bis(adamantan-2-yl)methyl]cyclopentadienyl}difluoridotitanium(IV), [Ti(C15H19)2F2], together with the bromide and iodide analogues, and the chloride analogues of the diphenylmethyl and adamantyl complexes. These eleven complexes were prepared by the reaction of the corresponding bis(η5:η1-pentafulvene)titanium complexes with different hydrogen halides (Cl, Br and I). The titanocene fluorides become available via chloride-fluoride exchange reactions.


Percutaneous nephrolithotomy: one stage or two?
Two hundred and fifty cases of percutaneous nephrolithotomy (PNL) are described. One hundred and fifty cases were treated in two stages, 100 in a single stage. The one-stage method has been shown to be as safe as the two-stage method but should be reserved for those with experience of the technique and who possess adequate instrumentation. PNL has proved to be a preferable option to open stone surgery and a useful alternative to extracorporeal shock wave lithotripsy (ESWL).


Deassociate the initial temporal phase deviation provided by photoelastic modulator for stroboscopic illumination polarization modulated ellipsometry.
In addition to operating the imaging ellipsometric measurements by four-specific temporal phases in the photoelastic modulated ellipsometry, we added the fifth one to solve the initial phase of the photoelastic modulator. This methodology has been developed to conquer the slow imaging processing of charge-coupled device camera for the stroboscopic illumination in the polarization modulated imaging ellipsometry. Without any calibration in its initial phase, we can perform the ellipsometric measurement by the measurements of intensity at five-specific temporal phases. The intensities of a full cycle for a point on SiO(2)∕Si thin film were measured and analyzed for verifying this algorithm. The five stroboscopic illuminations were performed to measure the two-dimensional distribution of the same SiO(2)∕Si thin film.


Natural Compound 3β,7β,25-trihydroxycucurbita-5,23(E)-dien-19-al from Momordica charantia Acts as PPARγ Ligand.
Momordica charantia is a popular vegetable associated with effective complementary and alternative diabetes management in some parts of the world. However, the molecular mechanism is less commonly investigated. In this study, we investigated the association between a major cucurbitane triterpenoid isolated from M. charantia, 3β,7β,25-trihydroxycucurbita-5,23(E)-dien-19-al (THCB) and peroxisome proliferator activated receptor gamma (PPARγ) activation and its related activities using cell culture and molecular biology techniques. In this study, we report on both M. charantia fruit crude extract and THCB in driving the luciferase activity of Peroxisome Proliferator Response Element, associated with PPARγ activation. Other than that, THCB also induced adipocyte differentiation at far less intensity as compared to the full agonist rosiglitazone. In conjunction, THCB treatment on adipocytes also resulted in upregulation of PPAR gamma target genes expression; AP2, adiponectin, LPL and CD34 at a lower magnitude compared to rosiglitazone's induction. THCB also induced glucose uptake into muscle cells and the mechanism is via Glut4 translocation to the cell membrane. In conclusion, THCB acts as one of the many components in M. charantia to induce hypoglycaemic effect by acting as PPARγ ligand and inducing glucose uptake activity in the muscles by means of Glut4 translocation.


Formation and stability of a nitric oxide donor: S-nitroso-N-acetylpenicillamine.
The formation, reaction dynamics, and detailed kinetics and mechanism of the reaction between nitrous acid and N-acetylpenicillamine (NAP) to produce S-nitroso-N-acetylpenicillamine (SNAP) was studied in acidic medium. The nitrous acid was prepared in situ by the rapid reaction between sodium nitrite and hydrochloric acid. The reaction is first order in nitrite and NAP. It is also first order in acid in pH conditions at or slightly higher than the pK(a) of nitrous acid. In lower pH conditions, the catalytic effect of acid quickly saturates. Higher acid concentrations also induce a faster decomposition rate of the SNAP, thus precluding the quantitative formation of SNAP from HNO2 and NAP. Both HPLC and quadrupole time-of-flight mass spectrometry techniques proved that SNAP was the sole product produced. No nitrosation occurred on the secondary amine center in NAP, and only the thiol group reacted to form the nitrosothiol. Cu(I) ions were found to be effective SNAP-decomposition catalysts. Cu(II) ions had no effect on the stability of SNAP. Ambient oxygen in reaction solutions was found to have no effect on initial rates of formation of SNAP, products obtained, and stability of SNAP. The formation of SNAP occurs through two distinct pathways. One involves the direct reaction of NAP and HNO2 to form SNAP and eliminate water, and the second pathway involved the initial formation of the nitrosyl cation, NO+, which then nitrosates the thiol. The bimolecular rate constant for the reaction of NAP and HNO2 was derived as 2.69 M(-1) s(-1), while that of direct nitrosation by the nitrosyl cation was 3.00 x 10(4) M(-1) s(-1). A simple reaction network made up of four reactions was found to be sufficient in simulating the formation kinetics and acid-induced decomposition of SNAP.


A Genetically Engineered Biofilm Material for SARS-CoV-2 Capturing and Isolation.
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously infecting people all around the world since its outbreak in 2019. Studies for numerous infection detection strategies are continuing. The sensitivity of detection methods is crucial to separate people with mild infections from people who are asymptomatic. In this sense, a strategy that would help to capture and isolate the SARS-CoV-2 virus prior to tests can be effective and beneficial. To this extent, genetically engineered biomaterials grounding from the biofilm protein of Escherichia coli are beneficial due to their robustness and adaptability to various application areas. Through functionalizing the E. coli biofilm protein, diverse properties can be attained such as enzyme display, nanoparticle production, and medical implant structures. Here, E. coli species are employed to express major curli protein CsgA and Griffithsin (GRFT) as fusion proteins, through a complex formation using SpyTag and SpyCatcher domains. In this study, a complex system with a CsgA scaffold harboring the affinity of GRFT against Spike protein to capture and isolate SARS-CoV-2 virus is successfully developed. It is shown that the hybrid recombinant protein can dramatically increase the sensitivity of currently available lateral flow assays for Sars-CoV-2 diagnostics.


Phylogenetic analysis of previously nontypeable hepatitis C virus isolates from Argentina.
Phylogenetic analysis of hepatitis C virus isolates from Argentina that were previously nontypeable by restriction fragment length polymorphism (RFLP) analysis revealed that they belong to genotype 1a. A substitution at position 107 (G-->A), which is the landmark of these strains, was shown to be distributed among isolates worldwide. The RFLP patterns obtained for these isolates should be added to the ones reported for genotype 1 isolates.


Autism spectrum disorder and mercury toxicity: use of genomic and epigenetic methods to solve the etiologic puzzle.
Autism spectrum disorder (ASD) is an increasingly prevalent neurodevelopmental condition of unknown etiology. Mercury is a common, highly neurotoxic heavy metal. The similarities of neurologic manifestations of mercury exposure and ASD raise an intriguing hypothetical question: Is ASD, at least partially, a manifestation of mercury toxicity? The fetus is particularly vulnerable to mercury exposure from the "double jeopardy" combination of the genetics of his mother and his own genetics, as relates to mercury toxicity. In this paper, I review the evidence suggesting relationships between ASD and mercury toxicity. I suggest ways to confirm these relationships with genetic and epigenetic research. I propose a hypothesis associating mercury toxicity with ASD. This may present opportunities for further research in prevention and treatment of ASD.


Combinations of genetic mutations in the adult neural stem cell compartment determine brain tumour phenotypes.
It has been suggested that intrinsic brain tumours originate from a neural stem/progenitor cell population in the subventricular zone of the post-natal brain. However, the influence of the initial genetic mutation on the phenotype as well as the contribution of mature astrocytes to the formation of brain tumours is still not understood. We deleted Rb/p53, Rb/p53/PTEN or PTEN/p53 in adult subventricular stem cells; in ectopically neurografted stem cells; in mature parenchymal astrocytes and in transplanted astrocytes. We found that only stem cells, but not astrocytes, gave rise to brain tumours, independent of their location. This suggests a cell autonomous mechanism that enables stem cells to generate brain tumours, whereas mature astrocytes do not form brain tumours in adults. Recombination of PTEN/p53 gave rise to gliomas whereas deletion of Rb/p53 or Rb/p53/PTEN generated primitive neuroectodermal tumours (PNET), indicating an important role of an initial Rb loss in driving the PNET phenotype. Our study underlines an important role of stem cells and the relevance of initial genetic mutations in the pathogenesis and phenotype of brain tumours.


Glomerular transplant rejection: a distinctive pattern of early graft damage.
Five hundred seventy-six consecutive biopsy or nephrectomy specimens obtained during the first 6 months of transplantation from 300 grafts in 431 recipients were examined by light microscopy for focal or diffuse endocapillary hypercellularity. Forty-seven (8.2%) of the 576 specimens obtained from 37 (12.3%) of the 300 grafts exhibited segmental or global occlusion of capillaries by swollen cells in 40-100% of glomeruli per biopsy. The lesions occurred at any time after transplantation, but 34 (72.3%) were present by day 60 and 7 (14.9%) before day 10. Immunofluorescence in 39 affected biopsies revealed focal or segmental glomerular staining in 18 (46.2%), among which IgM was found most frequently, and was considered to be non-specific. Electron micrographs of 17 biopsies from 14 grafts revealed that glomerular capillaries were narrowed or occluded by mononuclear cells of uncertain type, possibly monocytes, as well as lymphocytes and a few neutrophils. Complement-fixing antibody titers to cytomegalovirus rose at least fourfold in 10 (45.5%) of the 22 patients studied, but glomerular lesions were no more severe in the seroconverters than in the non-converters, and there was no consistent temporal relationship between the occurrence of glomerular changes and seroconversion. Cellular or vascular rejection was present in most biopsies. One year graft survival was 34% among 35 accessed grafts with glomerular lesions, compared to 55% among 243 biopsied grafts with no glomerular changes. We consider that these lesions do not have a consistent association with cytomegalovirus infection and that they represent a distinctive form of glomerular rejection. Whether they indicate a poor graft survival, as the present results suggest but do not prove, requires further studies of other series of cases.


Essential Role of NLRP3 Inflammasome in Mediating IL-1β Production and the Pathobiology of Staphylococcus aureus Endophthalmitis.
Staphylococcal endophthalmitis is one of the leading causes of blindness following ocular surgery and trauma. Dysregulated inflammation during bacterial endophthalmitis causes host-induced inflammatory damage and vision loss if it remains unchecked. Emerging evidence indicates that inflammasome plays a critical role in regulating innate immunity in various infectious and inflammatory diseases. However, the role of the inflammasome in endophthalmitis remains elusive. Here, using a mouse model of Staphylococcus (S) aureus endophthalmitis, we show that NLRP3/ASC/Caspase-1 signaling regulates IL-1β production in endophthalmitis. We also show that S. aureus and its cell wall components and toxins induce the activation of the NLRP3 inflammasome complex in mouse eyes. Moreover, we found that both infiltrating neutrophils and retinal microglia contribute toward NLRP3 activation and IL-1β production in S. aureus-infected eyes. Furthermore, our data using NLRP3-/- and IL-1β-/- mice revealed that NLRP3 and IL-1β deficiency leads to increased intraocular bacterial burden and retinal tissue damage. Altogether, our study demonstrated an essential role of NLRP3 inflammasome activation in regulating innate immune responses in bacterial endophthalmitis.


Splenic microabscesses in the immune-compromised patient.
Four immune-compromised children who were receiving antineoplastic chemotherapy (three for leukemia), presented with recurrent episodes of fever and left upper abdominal pain. Blood cultures grew enteric gram-negative organisms in three children. Multiple blood cultures were negative for fungus although three patients had mucocutaneous and urinary candidiasis. All remained febrile and symptomatic despite treatment with broad spectrum antibiotics and antifungal chemotherapy. Computed tomography (CT) scans in all patients showed 2- to 10-mm focal defects in the spleen. The larger defects could be seen by ultrasonography but not on the live-spleen nuclear scan. A splenectomy was performed 2 to 4 weeks after the onset of symptoms in each child, and the cut surface of the spleens showed multiple small abscesses. All operative cultures were negative. A histological examination confirmed Candida infection in two patients and Aspergillus in one. Necrotizing granulomas strongly suggestive of fungus were seen in the fourth child. The patients defervesced and appeared well within three days. Antifungal therapy was continued. One child remains in remission from acute lymphocytic leukemia; one continues on chemotherapy; and one has recurrent widespread tumor. The patient with Aspergillus died following a bone marrow transplantation 6 months after the splenectomy. He had disseminated aspergillosis. An immune-compromised patient with persistent unexplained fever should have a CT scan of the abdomen. The presence of multiple splenic lesions strongly suggests fungal disease. If antifungal therapy does not result in complete resolution of fever and the splenic lesions, a splenectomy is indicated.


Synthesis and antioxidant activities of some new triheterocyclic compounds containing benzimidazole, thiophene, and 1,2,4-triazole rings.
Various triheterocyclic compounds containing benzimidazole, thiophene, and 1,2,4-triazole rings (3-6) were synthesized and screened for their antioxidant activities. The structures of the synthesized compounds (2-6) were judged by (1)H NMR, (13)C NMR, elemental analysis, and LC-MS spectral data. Antioxidant activities of the synthesized compounds (2-6) were determined with CUPric Reducing Antioxidant Capacity (CUPRAC), ABTS (2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)/persulfate, and DPPH (1,1-diphenyl-2-picrylhydrazyl) assays. Most of the compounds showed a significant antioxidant activity and especially, compound 5c showed very good SC50 value for DPPH method and compound 5h exhibited very high scavenging activity to ABTS method.


Non-infantile intussusception.
In Europe and North America, most cases of non-infantile intussusception are associated with intestinal neoplasm. At the University College Hospital, Ibadan, Nigeria, the majority of cases of intussusception seen are ileocecocolic and cecocolic types. These are usually not associated with intestinal neoplasm and simple reduction is all that is required.Intussusception occurring in other segments of the intestinal tract is found to be associated with intestinal neoplasm, mesenteric lymphadenopathy, and ascaris worms. The very mobile cecum and ascending colon found in this population may be related to the high incidence of ileocecocolic and cecocolic intussusception.Indications for resection of intussusception include presence of intestinal neoplasm, irreducibility, gangrenous bowel, and chronicity.


Results of aortic valve-sparing operations.
To review the late results of valve-sparing operations in patients with aortic root aneurysm and in those with ascending aortic aneurysm and aortic insufficiency. From May 1988 to June 2000, 120 patients with aortic root aneurysm and 68 with ascending aortic aneurysm and aortic insufficiency underwent aortic valve-sparing operations. Patients with aortic root aneurysm were younger, were predominantly male, and had less severe aortic insufficiency than patients with ascending aortic aneurysm, who were older and often had aneurysm of the transverse arch. Forty-eight patients with aortic root aneurysm had the Marfan syndrome. The prevalence of aortic dissection was similar in both groups. Reconstruction of the aortic root was performed by reimplanation of the aortic valve in 64 patients and by remodeling of the aortic root in 56. Patients with ascending aortic aneurysm and aortic insufficiency were treated by replacement of the ascending aorta with reduction in the diameter of the sinotubular junction. Approximately two thirds of the latter patients also required replacement of the transverse aortic arch. The mean follow-up was 35 +/- 31 months for patients with aortic root aneurysm and 26 +/- 23 months for those with ascending aortic aneurysm. There were 2 operative and 5 late deaths in patients with aortic root aneurysm and 1 operative and 9 late deaths in patients with ascending aortic aneurysm. The 5-year survival for patients with aortic root aneurysm was 88% +/- 4% and for patients with ascending aortic aneurysm, 68% +/- 12% (P =.01). Severe aortic insufficiency developed in 2 patients, and they required aortic valve reoperation. The 5-year freedom from aortic valve reoperation was 99% +/- 1% for patients with aortic root aneurysm and 97% +/- 4% for those with ascending aortic aneurysm. Seven patients had moderate aortic insufficiency at the latest echocardiographic study. The 5-year freedom from severe or moderate aortic insufficiency was 90% +/- 4% in patients who had aortic root aneurysm and 98% +/- 2% in those who had ascending aortic aneurysm. Aortic valve-sparing operations have provided excellent clinical outcomes and few valve-related complications. The function of the reconstructed aortic root remains unchanged in most patients during the first 5 years of follow-up.


Rosuvastatin-Induced Dizziness and Pruritus: A Case Report and Summary of Statin-Associated Dizziness and Pruritus.
Drug-associated adverse events can present with varying symptoms, such as dizziness and pruritus. A 48-year-old woman initiated rosuvastatin to treat her elevated triglycerides. She developed rosuvastatin-associated adverse events, which included dizziness and pruritus within two weeks after starting treatment. After stopping the medication, the dizziness immediately cleared; the pruritus diminished during the next two weeks and eventually resolved completely. Side effects associated with rosuvastatin are discussed. The possibility of a medication-related etiology should be entertained when an individual suddenly develops either dizziness or pruritus or both.


[Mechanism of blood-activating and mass-dissipating Chinese patent medicine against hyperplasia of mammary glands and use with other medicine: a review].
Caused by endocrine disorder, hyperplasia of mammary glands(HMG) tends to occur in the young with increasing incidence, putting patients at the risk of cancer and threatening the health of women. Therefore, the prevention and treatment of HMG is attracting more and more attention. Amid the modernization of traditional Chinese medicine(TCM), many scholars have found that Chinese patent medicine has unique advantages and huge potential in treatment of endocrine disorder. Particularly, Chinese patent medicine with the function of blood-activating and mass-dissipating, such as Xiaojin Pills and Xiaozheng Pills, has been commonly used in clinical treatment of HMG, which features multiple targets, obvious efficacy, small side effect, and ease of taking and carrying around. Clinical studies have found that the combination of Chinese patent medicine with other medicine can not only improve the efficacy and relieve symptoms such as hyperplasia and pain but also reduce the toxic and side effects of western medicine. Therefore, based on precious pharmacological research and clinical research, this study reviewed the mechanisms of blood-activating mass-dissipating Chinese patent medicine alone and in combination with other medicine, such as regulating levels of in vivo hormones and receptors, promoting apoptosis, inhibiting angiogenesis, improving hemorheology indexes, enhancing immunity, and boosting antioxidant ability. In addition, limitations and problems were summarized. Thereby, this study is expected to lay a theoretical basis for the further study and clinical application of blood-activating mass-dissipating Chinese patent medicine alone or in combination with other medicine against HMG.


Effectiveness of renal denervation in the treatment of hypertension: a literature review.
Catheter-based renal denervation has been studied as a potential therapeutic option to reduce high blood pressure (BP). Preclinical studies in some experimental models have demonstrated an antihypertensive effect of renal denervation but reports from clinical trials have been mixed METHODS: We performed a literature search using combinations of the key terms 'Cardiovascular diseases, Clinical trial, Pre-clinical trials, Resistant hypertension, Renal denervation, Ablation technique, Radiofrequency ablation, Ultrasound ablation, RADIANCE SOLO, SYMPLICITY HTN, SYPRAL HTN'. The databases searched were PubMed and OVID Medline. The initial SYMPLICITY HTN-1 AND HTN-2 clinical trials reported significant decreases in office BP but results from the more robustly designed SYMPLICITY HTN-3 trial, which included sham controls and ambulatory BP monitoring, showed no significant antihypertensive effect. Interest in the use of renal denervation in hypertension was once again sparked by favourable results from the SPYRAL HTN-OFF Med trial CONCLUSION: We provide a thorough, critical analysis of key preclinical and clinical studies investigating the efficacy of catheter-based renal denervation as a treatment for hypertension and highlight future areas for research to allow better translation into clinical practice.


Mixed X-Site Formate-Hypophosphite Hybrid Perovskites.
Following the recent discovery of a new family of hybrid ABX3 perovskites where X=(H2 POO)- (hypophosphite), this work reports a facile synthesis for mixed X-site formate perovskites of composition [GUA]Mn(HCOO)3-x (H2 POO)x , with two crystallographically distinct, partially ordered intermediate phases with x=0.84 and 1.53, corresponding to ca. 30 and 50 mol % hypophosphite, respectively. These phases are characterised by single-crystal XRD and solid-state NMR spectroscopy, and their magnetic properties are reported.


An abattoir-based study on the prevalence of hydatidosis in livestock in Mashhad, Iran.
A 6-year (2004-2010) retrospective study was carried out to determine the prevalence of hydatidosis in livestock slaughtered in Mashhad abattoir, Mashhad, in north-eastern Iran and the capital of Khorasan province. Between 20 March 2004 and 19 March 2010, 5,131,485 animals (411,163 cattle; 4,547,618 sheep; 172,704 goats) were slaughtered in the study area and 388,399 (7.5%) livers and 1,139,529 (22.2%) lungs were discarded. Hydatidosis was responsible for 4% and 6.5% of total livers and lungs inspected, respectively. Of the cattle livers and lungs inspected over the survey period, 5.5% and 7.9% were condemned, respectively, because they held hydatid cysts. The corresponding values for livers and lungs of sheep (2%, 4%) and of goats (4.5%, 7.8%), respectively, were also condemned due to hydatidosis. Data showed a prominent seasonal pattern for hydatidosis. Liver condemnations due to hydatidosis were higher in winter and autumn for cattle and sheep, respectively, whereas lung condemnations were higher in summer for sheep and cattle. In goats, liver and lung condemnations were higher in winter. This could be attributed to various factors, such as sources of slaughtered animals, changes in management practice and ecological factors. The present survey provides baseline data for the future monitoring of this potentially important parasitic disease in the region.


Effects of ten milligrams of ampicillin per day on urinary tract infections.
A total of 20 patients with symptomatic urinary tract infections (greater than 10(5) colony-forming units of Escherichia coli per ml of urine in addition to pyuria) received 10 mg of ampicillin and 2 liters of fluid daily for 3 days. After 2 days, 16 patients had culture-negative urine without pyuria. A total of 18 similar patients received only 2 liters of fluid for 3 days. On day 4, all had greater than 10(5) colony-forming units of E. coli per ml of urine and greater than 10(4) leukocytes per mm3 of urine.


Quantitative Determination of Contribution by Enhanced Local Electric Field, Antenna-Amplified Light Scattering, and Surface Energy Transfer to the Performance of Plasmonic Organic Solar Cells.
Plasmonic metal nanostructures are widely used as subwavelength light concentrators to enhance light harvesting of organic solar cells through two photophysical effects, including enhanced local electric field (ELEF) and antenna-amplified light scattering (AALS), while their adverse quenching effect from surface energy transfer (SET) should be suppressed. In this work, a comprehensive study to unambiguously distinguish and quantitatively determine the specific influence and contribution of each effect on the overall performance of organic solar cells incorporated with Ag@SiO2 core-shell nanoparticles (NPs) is presented. By investigating the photon conversion efficiency (PCE) as a function of the SiO2 shell thickness, a strong competition between the ELEF and SET effects in the performance of the devices with the NPs embedded in the active layers is found, leading to a maximum PCE enhancement of 12.4% at the shell thickness of 5 nm. The results give new insights into the fundamental understanding of the photophysical mechanisms responsible for the performance enhancement of plasmonic organic solar cells and provide important guidelines for designing more-efficient plasmonic solar cells in general.


Phase estimation with weak measurement using a white light source.
We report results of a high precision phase estimation based on a weak measurement scheme using a commercial light-emitting diode. The method is based on a measurement of the imaginary part of the weak value of a polarization operator. The imaginary part of the weak value appeared due to the measurement interaction itself. The sensitivity of our method is equivalent to resolving light pulses of the order of a attosecond and it is robust against chromatic dispersion.


A Rapid Chemiluminescence Assay for Measurement of Folate in Small Volumes of Breast Milk.
Early life exposure to folate has long lasting effects on development and health. Newborns obtain part of their folate from maternal milk. Studies on health effects of milk folate require rapid, affordable and reliable measurements in large numbers of samples from cohort studies. Recently, a competitive chemiluminescence assay for quantification of folate has become available for automated diagnostic measurement of folate in human serum or plasma. We tested if this method ("FOLA" from Siemens Healthcare) could also be used for human milk. To minimize interference and matrix effects, samples had to be skimmed, diluted seven times with demineralized water, and heated for 5 min at 90 °C. Folate could thus be measured in a linear range between 8.4 and 111.7 nM, with recoveries for the most relevant form, 5-methyltetrahydrofolate (5-MeTHF), of 96%-107%. Results were comparable to those with a recently validated Liquid Chromatography/Mass Spectrometry method (Y = 0.998X - 0.2; R2 = 0.807). The FOLA method was subsequently used for samples from the LIFE Child cohort in Germany, providing first data of breast milk folate in this country (range: 6.2-100.7 nM). This technique could indeed prove useful for large cohorts with multiple samplings.


Incidence of mandibular nutrient canals in hypertensive patients: a radiographic study.
Hypertension, also called a 'silent killer,' is one of the most common medical problems seen in our profession. A prospective study was conducted in the Department of Oral Medicine and Radiology to determine the incidence of the appearance of nutrient canals in the periapical radiographs of the mandibular anterior region of patients with high blood pressure. A total of 100 patients, between 10-80 years, were examined. After taking a proper history, systemic and oral examinations were done and the findings were recorded under two categories, hypertensive patients and normotensive patients. They were further subdivided according to their periodontal status. Intraoral periapical radiographs of the lower anterior region were then taken. Radiographs were interpreted with a good X-ray viewer and the use of a magnifying glass. Findings were recorded on a prepared format.


Focal xanthogranulomatous pyelonephritis -- a diagnostic dilemma.
Focal Xanthogranulomatous Pyelonephritis (XGPN) may be erroneously interpreted as renal cell carcinoma. We report a case of a young Philippino who presented with persisting right flank pain for 2 years. Imaging showed a well-delineated lesion in the lower pole of the right kidney extending to the hilum. Nephrectomy was performed under a tentative diagnosis of renal cell carcinoma, whereas histology revealed focal XGPN. Pre-operative diagnosis of focal XGPN was difficult because of radiological similarities to renal cell carcinoma and lack of the usual clinical presentation.


Aptamer based electrochemical assay for the determination of thrombin by using the amplification of the nanoparticles.
A novel electrochemical assay based on the aptamer and the signal of amplification of nanoparticles (NPs) was constructed for the determination of thrombin. Aptamers immobilized on the electrode and Au NPs could be assembled with the target protein to form a sandwich structure in the presence of the latter. Differential pulse voltammetry (DPV) was employed to detect the CdS NPs loaded on the surface of the Au NPs through the linker DNA, which was related to the concentration of the target protein. The assay took advantage of the amplification ability of Au nanoparticles carrying multiplex CdS NPs and the specific affinity of aptamers. Thrombin was detected in this assay in the linear range of 1.0x10(-15) to 1.0x10(-11) M with the detection limit of 5.5x10(-16) M of target protein. In addition, the assay could be used to detection thrombin in real samples with high sensitivity and good selectivity.


Iraq and Afghanistan Veterans' Use of Veterans Health Administration and Purchased Care Before and After Veterans Choice Program Implementation.
The Veterans Choice Program (VCP), enacted by Congress after concerns surfaced about access, enables veterans to receive care outside Veterans Health Administration (VHA) facilities. Veterans who face long wait times, large driving distances, or particular hardships are eligible for VCP. Prior purchased care programs were comparatively limited in scope. We sought to describe utilization of VHA-provided and purchased outpatient care by veterans eligible for VCP before and after VCP implementation. We focused on veterans recently eligible for VHA as they are of particular policy relevance and might have less established care patterns. We identified all Iraq and Afghanistan veterans who were eligible for VCP in 2015. We tabulated their use of VHA and purchased outpatient care for 3 years before (FY2012-2014) and 1 year after VCP implementation (FY2015). Our study population consisted of 214,449 Iraq and Afghanistan veterans who were eligible for VCP due to wait-time, distance, or hardship issues. In the first year of the program, 3821 (2%) of these Iraq and Afghanistan veterans used non-VHA services through VCP. Per capita VHA utilization tended to decline slightly after VCP implementation, but these changes varied by type of outpatient care. There was low uptake of VCP services in the first year of the program. Data from additional years are needed to better understand the impact of this policy.


[Congenital malformations among offspring of the liquidators of the consequences from Chernobyl accident].
The frequency and the structure of congenital malformations at children of the liquidators of the consequences from Chernobyl accident, undergone to an external scale gamma-irradiation in dozes up to 25 cGy. In total is surveyed 2379 newborn at which is revealed 318 intrauterine development defects. The received results are compared to the earlier published data on birth of congenital malformations in families of the fathers who have undergone to an irradiation in connection with professional activity at the enterprises of a nuclear industry, with emergency irradiation, with irradiation as a result of explosions of nuclear bombs in Japan, and are discussed from positions of the basic rules (situations) of radiating genetics. Total frequency, the frequency of forms 21 of inherent defects of development, taken into account in the International register of congenital malformations and frequency 9 forms heaviest of congenital intrauterine development defects with the high contribution mutation components at children of the liquidators authentically is higher than on the average on Russian Federation. The dependence of the frequency congenital malformations at children from dozes of an irradiation of the fathers--liquidators is revealed. The curve of dependence of the frequency of congenital malformations from time, past after work up to copulation carries arched character with peak of rise of frequency of congenital malformations in 2-3 years and decrease in 6-7 years.


Endotracheal tube cuff ignited by electrocautery during tracheostomy.
A 64-year old female requiring prolonged ventilatory support was scheduled for an elective tracheostomy. Anesthesia consisted of surgical infiltration of 1% lidocaine and supplemental isoflurane. The patient was mechanically ventilated with an FIO2 of 1.0. An incision was made over the third and fourth tracheal rings. Opening the trachea with electrocautery resulted in a large leak around the endotracheal tube. The cuff was visualized through the tracheal incision and noted to be deflated. A small bleeder was coagulated on the tracheal ring. At this point, a flash fire occurred rising about one-inch high through the tracheal incision. The surgeon immediately covered the site with his hand. The anesthetist promptly disconnected the anesthesia circuit and removed the endotracheal tube. The surgeon inserted the tracheostomy tube and ventilation resumed. The fire lasted approximately 1-2 seconds. Dexamethasone 10 mg was administered intravenously. End-tidal CO2 and oxygen saturation levels were unchanged. The endotracheal tube was inspected. Approximately one-third to one-half of the cuff was charred. Proper management of an endotracheal tube fire includes stopping ventilation, disconnecting the oxygen source, removing the endotracheal tube, diagnosing injury, administering short-term steroids, administering antibiotics if indicated, providing ventilation and medical support as necessary and monitoring the patient for at least 24 hours. Extreme caution is necessary when using electrocautery in close proximity to an endotracheal tube. If electrocautery is used in close proximity to an endotracheal tube, an FIO2 of 0.3 or less with helium should be used.


The treatment of vulvar lichen sclerosus and female sexual dysfunction.
Women with lichen sclerosus (LS) are more likely to have dyspareunia, decreased orgasm, and decreased coital frequency as compared to unaffected women. It is unknown whether standard medical therapy to treat LS results in improved sexual functioning. To describe sexual function in women with LS and to assess if LS-associated sexual dysfunction decreases after appropriate medical therapy. Women enrolled in a double-blind trial 12-week trial comparing clobetasol vs. pimecrolimus for the treatment of LS were administered the Female Sexual Distress Scale (FSDS) upon enrollment and at the end of the trial. The difference in the total score on the FSDS between the two groups before and after treatment was assessed with a paired t-test. The change in mean FSDS score from baseline to 12 weeks. A total of 31 out of 36 enrolled women had adequate treatment of LS as determined by a dermatopathologist's evaluation of pre and post-treatment biopsy specimens. The mean baseline FSDS score for the clobetasol group was 29 and, post-treatment, it was 15 (P=0.001). In the pimecrolimus group, the mean baseline FSDS score was 27 and, post-treatment, it was 21 (P=0.001). Despite adequate treatment, women with LS continue to have significant sexual dysfunction as assessed by the FSDS.


Tellurium: A Rare Element with Influence on Prokaryotic and Eukaryotic Biological Systems.
Metalloid tellurium is characterized as a chemical element belonging to the chalcogen group without known biological function. However, its compounds, especially the oxyanions, exert numerous negative effects on both prokaryotic and eukaryotic organisms. Recent evidence suggests that increasing environmental pollution with tellurium has a causal link to autoimmune, neurodegenerative and oncological diseases. In this review, we provide an overview about the current knowledge on the mechanisms of tellurium compounds' toxicity in bacteria and humans and we summarise the various ways organisms cope and detoxify these compounds. Over the last decades, several gene clusters conferring resistance to tellurium compounds have been identified in a variety of bacterial species and strains. These genetic determinants exhibit great genetic and functional diversity. Besides the existence of specific resistance mechanisms, tellurium and its toxic compounds interact with molecular systems, mediating general detoxification and mitigation of oxidative stress. We also discuss the similarity of tellurium and selenium biochemistry and the impact of their compounds on humans.


Mixing Cells for Vascularized Kidney Regeneration.
The worldwide rise in prevalence of chronic kidney disease (CKD) demands innovative bio-medical solutions for millions of kidney patients. Kidney regenerative medicine aims to replenish tissue which is lost due to a common pathological pathway of fibrosis/inflammation and rejuvenate remaining tissue to maintain sufficient kidney function. To this end, cellular therapy strategies devised so far utilize kidney tissue-forming cells (KTFCs) from various cell sources, fetal, adult, and pluripotent stem-cells (PSCs). However, to increase engraftment and potency of the transplanted cells in a harsh hypoxic diseased environment, it is of importance to co-transplant KTFCs with vessel forming cells (VFCs). VFCs, consisting of endothelial cells (ECs) and mesenchymal stem-cells (MSCs), synergize to generate stable blood vessels, facilitating the vascularization of self-organizing KTFCs into renovascular units. In this paper, we review the different sources of KTFCs and VFCs which can be mixed, and report recent advances made in the field of kidney regeneration with emphasis on generation of vascularized kidney tissue by cell transplantation.


CO2 laser myringotomy in children with otitis media with effusion.
The study aimed to evaluate the clinical application of CO2 laser myringotomy in children with otitis media with effusion (OME) under topical anaesthesia in an office setting. Laser myringotomy was performed with the CO2 laser Otoscan (OtoLAM) in 54 children (73 ears) with OME. The procedure on the tympanic membrane was performed under topical anaesthesia using Bonain's solution or 10 per cent Xylocaine (lidocaine) solution for 30 minutes before surgery. A circular perforation was created with a power of 15 W, single pulse duration of 200 msec and a scanned area of 1.9 mm in diameter. The mean healing time was 2.51 weeks (range 1-5 weeks). Effusion content was not a predictive prognostic factor for perforation healing time. Perforation location over anterior inferior or posterior inferior quadrants was not a predictive factor for perforation healing time. Xylocaine was the more effective anaesthestic. The OME resolution rate was 73 per cent. Laser myringotomy provides intermediate duration middle-ear ventilation. It could be beneficial in selected children with OME.


The DEAD-box helicase Hlc regulates basal transcription and chromatin opening of stress-responsive genes.
Stress-responsive genes are lowly transcribed under normal conditions and robustly induced in response to stress. The significant difference between basal and induced transcription indicates that the general transcriptional machinery requires a mechanism to distinguish each transcription state. However, what factors specifically function in basal transcription remains poorly understood. Using a classic model stress-responsive gene (Drosophila MtnA), we found that knockdown of the DEAD-box helicase Hlc resulted in a significant transcription attenuation of MtnA under normal, but not stressed, conditions. Mechanistically, Hlc directly binds to the MtnA locus to maintain the accessibility of chromatin near the transcriptional start site, which allows the recruitment of RNA polymerase II and subsequent MtnA transcription. Using RNA-seq, we then identified plenty of additional stress-responsive genes whose basal transcription was reduced upon knockdown of Hlc. Taken together, these data suggest that Hlc-mediated basal transcription regulation is an essential and widespread mechanism for precise control of stress-responsive genes.


The role of dominant stenoses in bacterial infections of bile ducts in primary sclerosing cholangitis.
Primary sclerosing cholangitis (PSC) is characterized by progressive fibrotic inflammation and strictures of the biliary system. We studied the role of dominant stenoses in bacterial biliary infections and the effect of routine antibiotic administration with cholangiography. A prospective clinical trial without blinding or randomization. The endoscopy unit in a university hospital. Fifty patients with PSC entered and finished the study. A total of 103 endoscopic retrograde cholangiographies (ERC) was performed in 37 PSC patients with dominant stenosis and 13 controls with PSC but no dominant stenosis. After selective cannulation of the bile duct, bile samples were obtained during each procedure. All patients received systemic antibiotic treatment with ciprofloxacin for one week after ERC. Enteric bacteria were detected in the bile specimens of 15 out of 37 PSC patients (40.5%) with dominant stenosis but never in the absence of dominant stenosis (P=0.004). Positive cultures for enteric bacteria were associated with elevated serum C-reactive protein, high leukocyte counts in bile (P<0.05) and the deterioration of liver function assessed by increasing bilirubin levels during the follow-up period lasting a median of 7 months (P=0.06). Despite the high rate of susceptibility in vitro, ciprofloxacin treatment eradicated enteric bacteria in only two out of 12 cases. Bacterial infection of the bile ducts with dominant stenosis is a frequent finding and may play a role in the progression of PSC. Short-course antibiotic treatment is not very effective in eradicating acteria from the bile ducts.


Continuity and coordination of care: conceptual interface and nurses' contributions.
This is a theoretical-reflective study, with the objective of discussing the concepts of continuity and coordination of care, its conceptual interface and nurses' actions for its effectiveness in health services, based on international and national scientific publications. The concepts have been studied for decades and, although they are interrelated, they are used in a similar way, indicating a lack of conceptual understanding. The concept of continuity underwent paradigm shifts and began to adopt patients' perspectives. Currently, it involves interpersonal, longitudinal, management and informational domains. Coordination consists of establishing connections between the possible elements involved in care. It is classified as horizontal and vertical and is organized into categories: sequential, parallel and indirect. Nurses stand out through actions aimed at coordination and continuity at different levels of care, which contributes to strengthening a cohesive and people-centered care. The interface between concepts indicates that, in order to achieve integrated and continuous services, continuity and coordination of care need to be interconnected and act together.


Consumption of baits containing raccoon pox-based plague vaccines protects black-tailed prairie dogs (Cynomys ludovicianus).
Baits containing recombinant raccoon poxvirus (RCN) expressing plague antigens (fraction 1 [F1] and a truncated form of the V protein-V307) were offered for voluntary consumption several times over the course of several months to a group of 16 black-tailed prairie dogs (Cynomys ludovicianus). For comparison, another group of prairie dogs (n = 12) was injected subcutaneously (SC) (prime and boost) with 40 microg of F1-V fusion protein absorbed to alum, a vaccine-adjuvant combination demonstrated to elicit immunity to plague in mice and other mammals. Control animals received baits containing RCN without the inserted antigen (n = 8) or injected diluent (n = 7), and as there was no difference in their survival rates by Kaplan-Meier analysis, all of them were combined into one group in the final analysis. Mean antibody titers to Yersinia pestis F1 and V antigen increased (p < 0.05) in the vaccinated groups compared to controls, but titers were significantly higher (p < 0.0001) in those receiving injections of F1-V fusion protein than in those orally vaccinated with RCN-based vaccine. Interestingly, upon challenge with approximately 70,000 cfu of virulent Y. pestis, oral vaccination resulted in survival rates that were significantly higher (p = 0.025) than the group vaccinated by injection with F1-V fusion protein and substantially higher (p < 0.0001) than the control group. These results demonstrate that oral vaccination of prairie dogs using RCN-based plague vaccines provides significant protection against challenge at dosages that simulate simultaneous delivery of the plague bacterium by numerous flea bites.


[Abdominal adipose tissue--significance and methods of detection].
The presence of excess fat in the abdomen, out of proportion to total body fat, is associated with increased risk for cardiovascular and metabolic diseases and other complications of obesity. In regard to subcutaneous fat, accumulation of visceral abdominal adipose tissue is more associated with increased metabolic risk However, men have more visceral fat than premeno-pausal women. Compared with premenopausal women, postmenopausal women have 49% more intra-abdominal fat, regardless of age and total fat mass. MEASUREMENT OF ABDOMINAL FAT DEPOTS: Various anthropometric indicators have been suggested for measuring body fat distribution. All of them have advantages and disadvantages, in relation to their interpretation and use. Many are specified as ratios and are difficult to interpret biologically, whereas a change in body fat distribution may exhibit little or no change in the ratios. Waist circumference and sagittal abdominal diameter are good predictors of visceral fat. But, extreme individual variations in visceral to subcutaneous ratio demonstrate the limitations of external anthropometry. The best methods to estimate the amount of visceral fat are imaging techniques like computed tomography or magnetic resonance, but they are expensive and inconvenient in routine practice. Further investigations should provide a simple and optimal indicator of abdominal obesity which should correlate with the amount of viscelar fat and the risk.


Degradation and binding of atrazine in surface and subsurface soils.
Understanding the dissipation rates of chemicals in unsaturated and saturated zones of subsurface soils will help determine if reductions of concentrations to acceptable levels will occur. Chemical properties and microbial biomass and activity were determined for the surface (0-15 cm), lower root (50-105 cm), and vadose (175-220 cm) zones in a Huntington silty clay loam (Fluventic Hapludoll) collected from an agricultural field near Piketon, OH. The rates of sorption, mineralization, and transformation (formation of bound residues and metabolites) of atrazine were determined. Microbial activity was estimated from the mineralization of (14)C-benzoate. We observed decreased levels of nutrients (total organic carbon, N, and P) and microbial biomass with depth, while activity as measured with benzoate metabolism was higher in the vadose zone than in either the surface or the root zones. Sorption coefficients (K(f)) declined from 8.17 in the surface to 3.31 in the vadose zone. Sorption was positively correlated with organic C content. Rates of atrazine mineralization and bound residues formation were, respectively, 12-2.3-fold lower in the vadose than in the surface soil. Estimated half-lives of atrazine ranged from 77 to 101 days in the surface soil, but increased to over 900 days in the subsurface soils. The decreased dissipation of atrazine with increasing depth in the profile is the result of decreased microbial activity toward atrazine, measured either as total biomass or as populations of atrazine-degrading microorganisms. The combination of reduced dissipation and low sorption indicates that there is potential for atrazine movement in the subsurface soils.


High Blood Pressure-A High Risk Problem for Public Healthcare.
High blood pressure is the most common cardiovascular disease and the first one due to mortality risk. Prospective studies showed that, until 2025, the number of individuals with HBP will increase up to 1.56 billion in adults, of which more than two thirds will be found in poor countries or developing ones. In the present study, we evaluated the clinical and epidemiological aspects of HBP in a group of 3050 patients admitted in the Department of Cardiology of the Public Hospital of Caracal, Olt county. The study on the distribution of patients according to sex allowed us to observe that most patients suffering from HBP were women, while the distribution according to the social environment showed that more than 2/3 of high blood pressure patients came from the rural area. By studying the distribution of patients according to age, we observed that most HBP patients were aged over 60 years old (86.49%).


Growth and structure of Pd films on ZnO(0001).
The growth and structure of Pd films on ZnO(0001) were investigated using high resolution electron energy loss spectroscopy, x-ray photoelectron spectroscopy, and low energy electron diffraction. Vapor deposited Pd films at 300 K were found to follow a two-dimensional (2D) island growth mode, in which 2D metal islands are formed up to a critical coverage at which point growth occurs primarily in a layer-by-layer fashion on top of the islands. Heating to only 350 K was found to be sufficient to induce partial agglomeration of Pd films into three-dimensional particles. In addition to causing further agglomeration into particles, heating to 700 K resulted in partial reduction of the ZnO surface and the formation of a PdZn alloy.


24 year outcomes of hepatitis B vaccination in Hangzhou, China.
To evaluate the impact of the universal infant HepB vaccination program on hepatitis B virus infection in Hangzhou, China. Hepatitis B incidences and HepB vaccination rates of Hangzhou from 1990 to 2003 were acquired from the historical paper-documents, while which were derived from China Information System for Diseases Control and Prevention and Zhejiang Information System for Immunization Program respectively from 2004 to 2013. A serology survey among person aged 0-59 y was conducted in Hangzhou in 2006. Participants were selected by stratified, multi-stage random sampling. Serum specimens were tested for HBsAg, anti-HBs , anti-HBc , HBeAg and anti-HBe by ELISA. For the past 24 years, hepatitis B incidence and mortality of Hangzhou declined dramatically (χ(2) = 3.2 × 10(4); χ(2) = 172.443; both P for trend < 0.001). Both urban and rural incidence descended (χ(2)urban = 1.904 × 10(4); χ(2)rural = 1.633 × 10(4) ; both P for trend < 0.001).Hepatitis B patients mainly concentrated in 20-40 y old; workers and farmers were the main infection occupations, which was varies in different years (χ(2) = 1.619 × 10(3), P < 0.001). Significant association was found between incidence of hepatitis B and HepB vaccination rate (r = 0 .946, χ(2) = 11.813, Pfor trend = 0.001). A total of 5605 participants aged 0-59 y included in this serological survey. The prevalence of HBsAg, anti-HBs, anti-HBc, HBeAg and anti-HBe were 6.19%, 45.83%, 57.25%, 0.62%, and 4.37%, respectively. Hangzhou has successfully integrated the HepB into routine immunization programs and this has had a significant impact on decreasing the incidence of hepatitis B infection.


Lymphocytic choriomeningitis virus-induced mortality in mice is triggered by edema and brain herniation.
Although much is known about lymphocytic choriomeningitis virus (LCMV) infection and the subsequent immune response in its natural murine host, some crucial aspects of LCMV-mediated pathogenesis remain undefined, including the underlying basis of the characteristic central nervous system disease that occurs following intracerebral (i.c.) challenge. We show that the classic seizures and paresis that occur following i.c. infection of adult, immunocompetent mice with LCMV are accompanied by anatomical and histological changes that are consistent with brain herniation, likely of the uncal subtype, as a causative basis for disease and precipitous death. Both by water weight determinations and by magnetic resonance imaging of infected brain tissues, edema was detected only at the terminal stages of disease, likely caused by the leakage of cerebrospinal fluid from the ventricles into the parenchyma. Furthermore, death was accompanied by unilateral pupillary dilation, which is indicative of uncal herniation. While immunohistochemical analysis revealed periventricular inflammation and a loss of integrity of the blood-brain barrier (BBB), these events preceded seizures by 2 to 3 days. Moreover, surviving perforin knockout mice showed barrier permeability equivalent to that of moribund, immunocompetent mice; thus, BBB damage does not appear to be the basis of LCMV-induced neuropathogenesis. Importantly, brain herniation can occur in humans as a consequence of injuries that would be predicted to increase intracranial pressure, including inflammation, head trauma, and brain tumors. Thus, a mechanistic dissection of the basis of LCMV neuropathogenesis may be informative for the development of interventive therapies to prevent this typically fatal human condition.


Analysis of an unusual cluster of systemic reactions to subcutaneous specific immunotherapy with respiratory allergens in one allergy center.
Systemic reactions to subcutaneous immunotherapy occur despite all necessary precautions and experienced staff and should prompt a search for causative factors. We present an analysis of 11 reactions, 8 of them within a short period. The patients and reactions were evaluated regarding extract errors (composition, concentration), dosing errors, ignored contraindications to specific subcutaneous immunotherapy, introductions versus maintenance phase and accidental intravascular injection. No single or common cause could be identified. Statistical analysis suggests that exceptional clusters of systemic reactions such as these may be just random cumulations without identifiable cause.


Histochemical responses in the retina after acute blood loss.
Adult albino mice were bleed through the hearts by cardiac puncture under Nembutal anesthetic. 0.3 ml of blood was withdrawn form every animal. The retinae were then studied on a timed basis with succinic dehydrogenase histochemistry and alkaline phosphatase histochemistry. In control retinae, high SDH activities were localized in the inner segments, outer plexiform, inner plexiform, and ganglion cells layers and high alkaline phosphatase activities were localized in the ganglion cell layers and the vessels of the plexiform layers. Decrease in the enzymatic activities of both SDH and alkaline phosphatase in these layers were most evident 5h after bleeding. 9 to 24 h after bleeding, a compensatory increase was detected. 48 to 72 h after, the enzymatic activities decreased again. Reperfusion of experimental animals with 5% dextrose would increase the retinal enzymatic activities back to normal, even if the reperfusion was carried out as late as 48 h after bleeding.


The genetic architecture of adaptation under migration-selection balance.
Many ecologically important traits have a complex genetic basis, with the potential for mutations at many different genes to shape the phenotype. Even so, studies of local adaptation in heterogeneous environments sometimes find that just a few quantitative trait loci (QTL) of large effect can explain a large percentage of observed differences between phenotypically divergent populations. As high levels of gene flow can swamp divergence at weakly selected alleles, migration-selection-drift balance may play an important role in shaping the genetic architecture of local adaptation. Here, we use analytical approximations and individual-based simulations to explore how genetic architecture evolves when two populations connected by migration experience stabilizing selection toward different optima. In contrast to the exponential distribution of allele effect sizes expected under adaptation without migration (Orr 1998), we find that adaptation with migration tends to result in concentrated genetic architectures with fewer, larger, and more tightly linked divergent alleles. Even if many small alleles contribute to adaptation at the outset, they tend to be replaced by a few large alleles under prolonged bouts of stabilizing selection with migration. All else being equal, we also find that stronger selection can maintain linked clusters of locally adapted alleles over much greater map distances than weaker selection. The common empirical finding of QTL of large effect is shown to be expected with migration in a heterogeneous landscape, and these QTL may often be composed of several tightly linked alleles of smaller effect.


Zinner Syndrome: Ipsilateral Renal Agenesis and Seminal Vesicle Cyst Presenting With Bony Metastasis.
Zinner syndrome is a rare congenital triad of mesonephric duct abnormality encompassing unilateral renal agenesis or dysgenesis, ipsilateral seminal vesicle cyst, and ejaculatory duct obstruction. Literature has reported 214 cases, with the most common presentation being lower urinary tract symptoms and abdominal pain. Most cases are incidentally diagnosed, and MRI has been the choice of radiological diagnosis. We report the case of an 81-year-old male who presented with a three-month history of a fungating elbow lesion, elbow pain, and weight loss. Imaging revealed an ipsilateral seminal vesicle cyst, absent kidney, and ejaculatory duct obstruction, i.e., Zinner syndrome with bone metastasis. A bone biopsy revealed a urothelial primary, and cyst aspiration and cytology revealed spermatozoa and malignant cells representing an adenocarcinoma. This patient was managed with symptom control, radiotherapy to the elbow, and palliative chemotherapy, but later succumbed to the condition.


Crystallization and preliminary X-ray crystallographic studies of the mesophilic xylanase A from Bacillus subtilis 1A1.
Xylanases have been the focus of research owing to their industrial potential in animal feed production, food processing and pulp and paper processes. In order to obtain insight into the structural stability of family 11 xylanases, the mesophilic family 11 xylanase (beta-1,4-xylan xylanohydrolase; EC 184.108.40.206) from Bacillus subtilis 1A1 has been crystallized and diffraction data have been collected to 1.7 A. The crystals belong to the orthorhombic space group P2(1)2(1)2, with unit-cell parameters a = 50.93, b = 70.50, c = 40.05 A. The structure has been determined by molecular replacement, resulting in a crystallographic residual of 36.4% after rigid-body refinement.


Beyond our tribe: Developing a normative sense of group-transcendent fairness.
Human beings naturally prefer and support ingroup members more than outgroup members, but to what extent do we morally value equal treatment to ingroups and outgroups? Across four preregistered studies, we examined the development of "group-transcendent fairness," that is, the moral endorsement of allocating resources equally to ingroup members and outgroup members. We found that when allocating common resources to ingroup and outgroup members, American adults (N = 549) thought it was morally right to allocate equally instead of giving more to their family, political, or minimal ingroup members, across high and low stakes (Study 1). This normative sense of group-transcendent fairness develops gradually: 4- to 6-year-olds tended to endorse ingroup favoritism, whereas by age 8 or 9 children endorsed intergroup fairness (Studies 2-3, N = 214). Adults from China (N = 200)-a culture that values ingroup loyalty-also endorsed intergroup fairness as morally right, suggesting this moral value is not specific to western societies where egalitarianism is emphasized (Study 4). In contrast to the normative endorsement of intergroup fairness, participants in all studies did not predict most people to be fair across contexts, suggesting group-transcendent fairness was perceived more as a prescriptive than a descriptive norm (Studies 1-4). Together, our studies reveal the robust presence of group-transcendent fairness, which is valued across group contexts and cultures, develops later than ingroup support, and is prescriptive but not descriptive by nature. The findings help illuminate the nature and development of one group-transcendent moral value that helps promote intergroup relations and societal progress. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


The dubious value of cerebrospinal fluid adenosine deaminase measurement for the diagnosis of tuberculous meningitis.
The diagnosis of tuberculous meningitis (TBM) can be extremely difficult in the absence of culture confirmation. Cerebrospinal fluid (CSF) adenosine deaminase (ADA) can potentially assist in this regard, although its current value remains unclear. The literature on the usefulness of CSF ADA in TBM diagnosis is inconsistent, especially from an analytical point of view. A retrospective analysis of clinical and laboratory data relating to all CSF ADA requests during 2009 and 2010 in a South African quaternary healthcare setting was performed. A CSF ADA cut-off for TBM diagnosis was calculated using receiver operating characteristic curve analysis. The performance of CSF ADA in different infective and non-infective categories was assessed. In total, 3548 CSF ADA requests were considered over the 2-year period. Of these, 1490 were for patients for whom both a CSF ADA and a mycobacterial culture were requested. The optimal cut-off was calculated at 2.0 U/L (AUC = 0.86; 95% CI = 0.82 - 0.89; p-value < 0.01; sensitivity of 85.9% (95% CI of 77.0 - 92.3) and specificity of 77.7% (95% CI of 75.4 - 79.8%); positive likelihood ratio = 3.85 and negative likelihood ratio = 0.18). At this cut-off 13 TBM cases were missed. An optimal cut-off for routine use could not be established as too many TBM cases were missed. Specimen integrity, lack of ADA assay standardisation and overlap in performance of the assay in different diagnostic categories affect interpretation.


[Advantages of the 5 MHz transducer in the diagnosis of non-palpable breast cancer].
We surveyed more than 800 neoplastic lesions studied by US in our department. Fifty-five were non-palpable (T0) tumors. In 60% of the cases, positivity or high suspicion of malignancy was demonstrated by US. If the doubtful cases (one sign of positivity), are added, the diagnostic rate is 67%. In the same series, X-ray mammography including positive, suspicions and doubtful cases reached the same percentage, giving together a final score of 89%. The method use is briefly described and the particular contribution of the 5 MHz mono-transducer is emphasized. The complementary of X-ray mammography and US studies in the diagnosis of T0 breast neoplasms is stressed.


Opportunities and challenges in using instrumental variables to study causal effects in nonrandomized stress and trauma research.
Researchers are often interested in assessing the causal effect of an exposure on an outcome when randomization is not ethical or feasible. Estimating causal effects by controlling for confounders can be unconvincing because important potential confounders remain unmeasured. Study designs leveraging instrumental variables (IVs) offer alternatives to confounder-control methods but are rarely used in stress and trauma research. We review the conceptual foundations and implementation of IV methods. We discuss strengths and limitations of IV approaches, contrasting with confounder-control methods, and illustrate the relevance of IVs for stress and trauma research. IV approaches leverage an external or exogenous source of variation in the exposure. Instruments are variables that meet three conditions: relevance (variation in the IV is associated with variation in the chance of exposure), exclusion (the IV only affects the outcome through the exposure), and exchangeability (no unmeasured confounding of the IV-outcome relationship). Interpreting estimates from IV analyses requires an additional assumption, such as monotonicity (the instrument does not change the chance of exposure in different directions for any two individuals). Valid IVs circumvent the need to correctly identify, measure, and control for all confounders of the exposure-outcome relationship. The primary challenge is identifying a valid instrument. IV approaches have strengths and weaknesses compared with confounder-control approaches. IVs offers a promising complementary study design to improve evidence about the causal effects of exposures on outcomes relevant to stress and trauma. Collaboration with scientists who are experienced with identifying and analyzing IVs will support this work. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Osthole inhibits inflammatory cytokine release through PPARα/γ-mediated mechanisms in LPS-stimulated 3T3-L1 adipocytes.
Peroxisome proliferator-activated receptor (PPAR) α/γ may control inflammatory response by regulating the nuclear factor-kappa B (NF-κB). Osthole may be a dual agonist of PPARα/γ, but whether or not osthole may inhibit inflammatory cytokines in cultured 3T3-L1 adipocytes is unclear. We investigated the action of osthole and its potential mechanisms in lipopolysaccharide (LPS)-stimulated 3T3-L1 adipocytes. The 3T3-L1 adipocytes stimulated with LPS were cultured and treated with different concentrations of osthole. The inflammatory cytokines including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cultured supernatants were detected by the enzyme-linked immunosorbent assay (ELISA) method, and the protein expressions of PPARα/γ and NF-κB p65 in adipocytes were detected by the Western blot method, respectively. Following treatment of adipocytes with osthole 0.1-1.6 μM, the TNF-α and IL-6 levels in cultured supernatants were decreased, and the NF-κB p65 protein expression in adipocytes was also decreased, while the PPARα/γ protein expressions were increased. After pretreatment of adipocytes with specific inhibitor(s) of PPARα and /or PPARγ, the inhibitory effects of osthole on TNF-α and IL-6 were decreased or almost cancelled, and the effects on NF-κB p65 protein expression also exhibited similar variations. Osthole could inhibit the TNF-α and IL-6 production in LPS-stimulated adipocytes, and its mechanism might be related to reduction of NF-κB expression via activation of PPARα/γ.


Drug eruption due to bosentan in a patient with systemic sclerosis.
We present the case of a 60-year-old female patient with systemic sclerosis complicated by pulmonary hypertension. Ten days after the initiation of treatment with bosentan, high fever and skin eruptions were noted. In the previous reports, the frequency of drug-induced skin eruptions has not been well documented. Since the use of bosentan is expected to increase, we should be aware of the previously unknown adverse effects as well as skin eruptions.