Electron-phonon coupling assisted emission in single magnetic La0.67Ca0.33MnO3 domains of thin nanoplates.
A chemical method with small polymer templates is explored to obtain single magnetic domain La0.67Ca0.33MnO3 particles of thin nanoplates (25-35 nm thickness). The sample is light-emitting (480-800 nm) in multiple bands with two prominent bandgroups in the 570 nm green and 762 nm red emissions. The green emission consists of four bands 555.1, 565.7, 573.4, and 584.7 nm in the O2- -2p--> Mn3+ / Mn4+ -3d interband electronic transitions. Two excited-electronic levels G, (565.7 nm) and G2 (555.1 nm), which are exchange coupled via a phonon level v2* (678 cm(-1)), exhibit the four bands in the transitions to the ground state G0 and a phonon level v1 (575 cm(-1)). The bands v1 and v2 are well-resolved in the IR spectrum. A similar phonon assisted Mn3+ --> Mn4+ charge transfer transition results in the red emission. Both the green and red bandgroups appear in a common excitation over 350-450 nm from a xenon source. Evidently, as proposed with a model energy level diagram, the electron-phonon coupling governs a multiple light-emission in this example of the single domain particles. Otherwise, such specific ceramics of half-metallic ferromagnets hardly allows a light-emission at room temperature.


A randomized pilot trial of dietary modification for the chemoprevention of noninvasive bladder cancer: the dietary intervention in bladder cancer study.
Epidemiological data suggest robust associations of high vegetable intake with decreased risks of bladder cancer incidence and mortality, but translational prevention studies have yet to be conducted. We designed and tested a novel intervention to increase vegetable intake in patients with noninvasive bladder cancer. We randomized 48 patients aged 50 to 80 years with biopsy-proven noninvasive (Ta, T1, or carcinoma in situ) urothelial cell carcinoma to telephone- and Skype-based dietary counseling or a control condition that provided print materials only. The intervention behavioral goals promoted seven daily vegetable servings, with at least two of these as cruciferous vegetables. Outcome variables were self-reported diet and plasma carotenoid and 24-hour urinary isothiocyanate (ITC) concentrations. We used two-sample t tests to assess between-group differences at 6-month follow-up. After 6 months, intervention patients had higher daily intakes of vegetable juice (P = 0.02), total vegetables (P = 0.02), and cruciferous vegetables (P = 0.07); lower daily intakes of energy (P = 0.007), fat (P = 0.002) and energy from fat (P = 0.06); and higher plasma α-carotene concentrations (P = 0.03). Self-reported cruciferous vegetable intake correlated with urinary ITC concentrations at baseline (P < 0.001) and at 6 months (P = 0.03). Although urinary ITC concentrations increased in the intervention group and decreased in the control group, these changes did not attain between-group significance (P = 0.32). In patients with noninvasive bladder cancer, our novel intervention induced diet changes associated with protective effects against bladder cancer. These data show the feasibility of implementing therapeutic dietary modifications to prevent recurrent and progressive bladder cancer.


Training a U-Net based on a random mode-coupling matrix model to recover acoustic interference striations.
A U-Net is trained to recover acoustic interference striations (AISs) from distorted ones. A random mode-coupling matrix model is introduced to generate a large number of training data quickly, which are used to train the U-Net. The performance of AIS recovery of the U-Net is tested in range-dependent waveguides with nonlinear internal waves (NLIWs). Although the random mode-coupling matrix model is not an accurate physical model, the test results show that the U-Net successfully recovers AISs under different signal-to-noise ratios and different amplitudes and widths of NLIWs for different shapes.


Development of a standardized training program for the Hamilton Depression Scale using internet-based technologies: results from a pilot study.
Poor inter-rater reliability is a major concern, contributing to error variance, which decreases power and increases the risk for failed trials. This is particularly problematic with the Hamilton Depression Scale (HAMD), due to lack of standardized questions or explicit scoring procedures. Establishing standardized procedures for administering and scoring the HAMD is typically done at study initiation meetings. However, the format and time allotted is usually insufficient, and evaluation of the trainee's ability to actually conduct a clinical interview is limited. To address this problem, we developed a web-based, interactive rater education program for standardized training to diverse sites in multi-center trials. The program includes both didactic training on scoring conventions and live, remote observation of trainees applied skills. The program was pilot tested with nine raters from a single site. Results found a significant increase in didactic knowledge pre-to-post testing, with the mean number of incorrect answers decreasing from 6.5 (S.D.=1.64) to 1.3 (S.D.=1.03), t(5)=7.35, P=0.001 (20 item exam). Seventy-five percent of the trainees' interviews were within two points of the trainer's score. Inter-rater reliability (intraclass correlation) (based on trainees actual interviews) was 0.97, P<0.0001. Results support the feasibility of this methodology for improving rater training. An NIMH funded study is currently underway examining this methodology in a multi-site trial.


Genetic analysis of feet and leg conformation traits in Nelore cattle.
Feet and leg conformation scores are important traits in beef cattle because they encompass a wide range of locomotion disorders that can lead to productive and reproductive losses. Thus, the study of feet and legs in beef cattle is essential for evaluating possible responses to selection focusing on minimizing economic losses caused by the occurrence of feet and leg problems. The aim of this study was to estimate variance components for feet and leg conformation traits in Nelore cattle. The data set contained records of approximately 300,000 animals that were born between 2000 and 2013. These animals belonged to the commercial beef cattle breeding program of the CRV Lagoa (). Feet and legs were evaluated by assigning visual scores at 2 different time points: feet and leg evaluated as a binary trait (FL1), measured at yearling (about 550 d of age) to identify whether (or not) an animal has feet and leg defects, and feet and leg score (FL2), ranging from 1 (less desirable) to 5 (more desirable) was assigned to the top 20% of animals according to the selection index adopted by the beef cattle breeding program, which was measured 2 to 5 mo after the yearling evaluation. The FL1 and FL2 traits were analyzed together with yearling weight (YW). The (co)variance components and breeding values were estimated by Bayesian inference using 2-trait animal models. The posterior means (standard errors) of the heritabilities for FL1, FL2, and YW were 0.18 (0.04), 0.39 (0.07), and 0.47 (0.01), respectively. The results indicate that the incidence of feet and leg problems in this population might be reduced by selection. The genetic correlation between FL1 and FL2 (-0.47) was moderate and negative as expected because the classification score that holds up each trait has opposite numerical values. The genetic trends estimated for FL1 and FL2 (-0.042 and 0.021 genetic standard deviations per year, respectively) were favorable and they indicate that the independent culling strategy for feet and leg problems promotes favorable changes and contributes to the genetic progress of these traits in the population under study.


Positive rK39 serologic assay results in US servicemen with cutaneous leishmaniasis.
The rK39 test is a serologic assay for the rapid diagnosis of visceral leishmaniasis (VL). Serum from a North American cohort of 59 otherwise asymptomatic soldiers with cutaneous leishmaniasis (CL) was tested with the rK39 dipstick and ELISA assays, and 10.2% and 28.8% had positive results, respectively. CL is associated with a reactive rK39 assay result in some patients without clinical evidence of VL.


Assessment of in-depth degradation of artificially aged triterpenoid paint varnishes using nonlinear microscopy techniques.
The present work investigates the applicability of nonlinear imaging microscopy for the precise assessment of degradation of the outer protective layers of painted artworks as a function of depth due to aging. Two fresh and artificially aged triterpenoid varnishes, dammar and mastic, were tested. Nonlinear imaging techniques have been employed as a new diagnostic tool for determination of the exact thickness of the affected region due to artificial aging of the natural varnishes. The measured thicknesses differ from the calculated mean penetration depths of the samples. These nondestructive, high resolution modalities are valuable analytical tools for aging studies and they have the potential to provide unique in-depth information. Single photon laser induced fluorescence measurements and Raman spectroscopy were used for the integrated investigation and analysis of aging effects in varnishes.


Brain-type creatine phosphokinase serum levels before and after ECT.
Brain-type creatine phosphokinase isoenzyme (CPK BB) was measured by radioimmunoassay in the serum of 31 depressed patients undergoing bilateral ECT. Samples were taken shortly before and at one hour, two hours, and six hours following ECT. ECT did not cause a significant alteration in serum CPK BB concentration during the six hours following the treatment. Similarly, there was no difference in mean pre-ECT concentration of serum CPK BB between patients receiving the first ECT of their current admission and those receiving subsequent treatments. These findings do not support suggestions that ECT causes alteration in permeability of the blood-brain barrier, nor that it causes detectable brain injury.


Targeted Perioperative Nursing Combined with Propofol and Fentanyl for Gynecological Laparoscopic Surgery.
The aim of this study is to investigate the clinical effects of targeted perioperative nursing combined with propofol and fentanyl in gynecological laparoscopic surgery. Patients who were admitted to our hospital for gynecological laparoscopic surgeries from October 1, 2019 to November 30, 2021 were included in this retrospective study. Patients in group A received routine propofol and fentanyl. Patients in group B received targeted perioperative nursing on the basis of interventions in group A. The anesthetic effects, clinical indicators, mental health status, and adverse reactions were compared between the two groups. A total of 84 qualified patients were retrieved. The total effective anesthesia rate, extubation time, operation time, consciousness recovery time, intraoperative blood loss, hospital stay, SAS score, SDS score, health status indicators, and adverse events in group B were all significantly better than those in group A (P < 0.05 for all comparisons). Combined intervention (propofol + fentanyl + targeted perioperative care) for gynecological laparoscopic surgery patients has a significant anesthesia effect, which can effectively improve the patient's clinical indicators and mental health status and can also reduce the occurrence of adverse events. It has good safety and can be widely used in clinical practice.


Clinical significance of microRNA-449a in hepatocellular carcinoma with microarray data mining together with initial bioinformatics analysis.
Increasing evidence has demonstrated that microRNA (miR)-449a expression is reduced in various types of tumors and that it serves as a tumor suppressor. However, the molecular mechanism of miR-449a in hepatocellular carcinoma (HCC) has not been thoroughly elucidated and is disputed. Therefore, the aim of the present work was to systematically review the current literature and to utilize the public Gene Expression Omnibus database to determine the role of miR-449a and its significance in HCC. A total of eight original papers and seven microarrays were included in the present study. Based on the evidence, miR-449a was reduced in HCC. miR-449a is likely involved in various signaling pathways and is targeted to multiple mRNA as part of its function in HCC. In addition, a preliminary bioinformatic analysis was conducted for miR-449a to investigate the novel potential pathways that miR-449a may participate in regarding HCC.


Janus kinase/signal transducer and activator of transcription inhibitors enhance the protective effect mediated by tanshinone IIA from hypoxic/ischemic injury in cardiac myocytes.
Tanshinone IIA is a lipophilic abietane diterpene compound, which exhibits protective effects against ischaemia/reperfusion injury; however, the pathways responsible for the myocardial protective activities of tanshinone IIA remain to be elucidated. The aim of the present study was to investigate the effect of tanshinone IIA on the Janus‑activated kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway, which is associated with cardiac dysfunction during ischemia/reperfusion. The results demonstrated that tanshinone IIA protected myocardial cells from hypoxia/ischemia‑induced injury in vitro and recovered decreased cell viability due to activation of the JAK2/STAT3 pathway, with 10 µM tanshinone IIA exhibiting the most potent protective effects. Flow cytometric analysis revealed that tanshinone IIA reversed the apoptotic aggravation induced by JAK2/STAT3 inhibitors following hypoxic ischemia. However, JAK2 inhibitors promoted the myocardial protective effect of tanshinone IIA from hypoxic‑ischemic injury. Furthermore, tanshinone IIA and JAK2/STAT3 inhibitors in combination augmented the protection of myocardial cells from apoptosis induced by ischemia/reperfusion preconditioning in vivo. In conclusion, the results of the present study indicated that JAK2/STAT3 inhibitors may enhance the protective effect of tanshinone IIA on cardiac myocytes from hypoxic ischemia-induced injury, therefore suggesting that JAK2/STAT3 inhibitors may have a potential application in combination therapies with tanshinone IIA.


Repair of ruptured abdominal aortic aneurysm after cardiac arrest.
Cardiac arrest in patients with ruptured abdominal aortic aneurysm (rAAA) is not uncommon and associated with significantly increased mortality. Although it has been suggested as a contraindication to aortic repair, the prognostic implications of preoperative cardiac arrest in the face of rAAA are controversial. The purpose of this structured review is to analyze the reported outcomes of patients with rAAA and preoperative cardiac arrest. English language single- and multi-institutional series reporting outcomes of patients with rAAA and cardiac arrest were identified by systematic literature search and review. An aggregate analysis and structured review of outcomes after subsequent aortic repair was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. The primary outcome was short-term overall mortality. Sixteen studies involving 2669 patients with rAAA were analyzed, including 334 (13%) with preoperative cardiac arrest. Cardiac arrest was associated with significantly increased mortality compared with patients with rAAA without arrest (86% vs 44%; P < .0001), although cardiac arrest in isolation was poorly predictive of mortality. Four patients were treated by endovascular aortic repair, and all survived. Shorter resuscitation times and return of signs of life prior to aortic repair are associated with improved survival, and long-term functional outcomes among survivors have been reported. Mortality among patients with rAAA and preoperative cardiac arrest is high but not prohibitive. Aortic repair should not be withheld from such patients who are otherwise reasonable candidates for intervention, provided resources for emergent aortic repair are available.


Development of 3D hydrogel culture systems with on-demand cell separation.
Recently there has been an increased interest in the effects of paracrine signaling between groups of cells, particularly in the context of better understanding how stem cells contribute to tissue repair. Most current 3D co-culture methods lack the ability to effectively separate two cell populations after the culture period, which is important for simultaneously analyzing the reciprocal effects of each cell type on the other. Here, we detail the development of a 3D hydrogel co-culture system that allows us to culture different cell types for up to 7 days and subsequently separate and isolate the different cell populations using enzyme-sensitive glues. Separable 3D co-culture laminates were prepared by laminating PEG-based hydrogels with enzyme-degradable hydrogel adhesives. Encapsulated cell populations exhibited good segregation with well-defined interfaces. Furthermore, constructs can be separated on-demand upon addition of the appropriate enzyme, while cell viability remains high throughout the culture period, even after laminate separation. This platform offers great potential for a variety of basic cell signaling studies as the incorporation of an enzyme-sensitive adhesive interface allows the on-demand separation of individual cell populations for immediate analysis or further culture to examine persistence of co-culture effects and paracrine signaling on cell populations.


International Spinal Cord Injury: Spinal Interventions and Surgical Procedures Basic Data set.
Survey of expert opinion, feedback and final consensus. To describe the development and the variables included in the International Spinal Cord Injury (SCI) Spinal Interventions and Surgical Procedures Basic Data set. International working group. A committee of experts was established to select and define data elements. The data set was then disseminated to the appropriate committees and organizations for comments. All suggested revisions were considered and both the International Spinal Cord Society and the American Spinal Injury Association endorsed the final version. The data set consists of nine variables: (1) Intervention/Procedure Date and start time (2) Non-surgical bed rest and external immobilization, (3) Spinal intervention-closed manipulation and/or reduction of spinal elements, (4) Surgical procedure-approach, (5) Date and time of the completion of the intervention or surgical closure; (6) Surgical procedure-open reduction, (7) Surgical procedure-direct decompression of neural elements, and (8 and 9) Surgical procedure-stabilization and fusion (spinal segment number and level). All variables are coded using numbers or characters. Each spinal intervention and procedure is coded (variables 1 through 7) and the spinal segment level is described (variables 8 and 9). Sample clinical cases were developed to illustrate how to complete it. The International SCI Spinal Interventions and Surgical Procedures Basic Data Set was developed to facilitate comparisons of spinal interventions and surgical procedures among studies, centers and countries.


Feasibility of home infusion and self-administration of nanofiltered C1 esterase inhibitor for routine prophylaxis in patients with hereditary angioedema and characterization of a training and support program.
Hereditary angioedema (HAE) is a rare, chronic disease of C1 inhibitor deficiency. Study researchers evaluated the prevalence of home and self-administration of nanofiltered, human-derived C1 esterase inhibitor infusions and the implementation of a nursing training and support program. Home administration rate increased from 49.0% to 75.8%. The percentage who self-administered increased from 20.3% to 43.9%. Doses per week averaged 1.85 at home compared with 1.40 in infusion centers and physicians' offices. Patients required an average of 5 visits to be trained. Self-administration is a viable, feasible option in the management of HAE, which is facilitated by a nurse-managed training and support program.


[Roles of long non-coding RNAs in prostate cancer and their action mechanisms].
Prostate cancer (PCa) is one of the most common male malignancies as well as one of the frequent causes of tumor-induced death. Long non-coding RNAs (lncRNAs) are RNA transcripts that are more than 200 nucleotides in length, lack an open reading frame, and do not encode proteins. LncRNAs are abnormally expressed in most tumors including PCa and closely related to the recurrence, metastasis and prognosis of PCa. LncRNAs regulate gene expressions at multiple levels such as epigenetics, transcription and post-transcription, change metabolic pathways, and play a carcinogenic or anti-tumor role in the development and progression of PCa. Continuous androgen receptor (AR) signal transduction is one of the key features of castration-resistant PCa. This review briefly introduces the role of lncRNAs as oncogenes or tumor suppressor genes in the development and progression of PCa, and expounds the possible molecular mechanisms of lncRNAs mediating PCa through the AR signaling pathway, post-transcriptional regulation represented by ceRNA, and tumor metabolism, aiming to provide potential biomarkers and therapeutic targets for the clinical diagnosis and treatment of PCa.


Kinin-B1 Receptor Stimulation Promotes Invasion and is Involved in Cell-Cell Interaction of Co-Cultured Glioblastoma and Mesenchymal Stem Cells.
Glioblastoma multiforme (GBM) represents the most lethal brain tumour, and these tumours have very limited treatment options. Mesenchymal stem cells (MSC) are considered as candidates for advanced cell therapies, due to their tropism towards GBM, possibly affecting their malignancy, thus also representing a potential therapeutic vector. Therefore, we aimed to compare the effects of bone-marrow-derived versus adipose-tissue-derived MSC (BM-/AT-MSC) on heterogeneous populations of tumour cells. This cells' interplay was addressed by the in-vitro two-dimensional (monolayer) and three-dimensional (spheroid) co-culture models, using U87 and U373 GBM cell lines, expressing genotypically different mesenchymal transcriptome profiles. U87 cell low mesenchymal profile expressed high levels of kinin receptor 1 (B1R) and their invasion was greatly enhanced by the B1R agonist des-Arg9-bradykinin upon BM-MSC co-culturing in 3D co-cultures. This correlated to significantly higher cell-cell interactions in U87/BM-MSC mixed spheroids. This was not observed with the U373 cells and not in AT-MSC co-cultures. Altogether, these data support the on-going exploration of B1R as target for adjuvant approach in GBM therapy. Secondly, the results emphasize the need for further careful exploration of the selectivity regarding the origin of MSC as potential candidates for cell therapies, particular in cancer, where they may adversely affect heterogeneous tumour cell populations.


Improved Dyson series expansion for steady-state quantum transport beyond the weak coupling limit: divergences and resolution.
We present a general theory to calculate the steady-state heat and electronic currents for nonlinear systems using a perturbative expansion in the system-bath coupling. We explicitly demonstrate that using the truncated Dyson-series leads to divergences in the steady-state limit, thus making it impossible to be used for actual applications. In order to resolve the divergences, we propose a unique choice of initial condition for the reduced density matrix, which removes the divergences at each order. Our approach not only allows us to use the truncated Dyson-series, with a reasonable choice of initial condition, but also gives the expected result that the steady-state solutions should be independent of initial preparations. Using our improved Dyson series we evaluate the heat and electronic currents up to fourth-order in system-bath coupling, a considerable improvement over the standard quantum master equation techniques. We then numerically corroborate our theory for archetypal settings of linear systems using the exact nonequilibrium Green's function approach. Finally, to demonstrate the advantage of our approach, we deal with the nonlinear spin-boson model to evaluate heat current up to fourth-order and find signatures of cotunnelling process.


Understanding the pathway between work and health outcomes for women during the preconception, pregnancy, and postpartum periods through the framing of maternal obesity.
The link between work and health outcomes for preconception, pregnant, and postpartum (PPP) working women is complex. Further, innovation and enhanced understanding are required to address the work-related determinants of maternal obesity. However, workplace health promotion is not typically systems-based nor attuned to the specific needs and context of individual PPP women. We propose that to improve health outcomes for PPP women, we must understand the pathways between paid work and health for the individual woman by taking a systems-thinking approach. In this paper, we (a) outline the rationale for why the oversimplification or "dilution" of individual context may occur; (b) present a systems-informed pathway model (the "Context-Exposure-Response" Model) and overview of potential work-related impacts on health and wellbeing outcomes for PPP women using maternal obesity to provide context examples; (c) further investigate the role of motivational factors from a systems perspective; and (d) briefly examine the implications for policy, practice, and intervention design. It is anticipated that this research may act as a starting point to assist program developers, researchers, and policymakers to adopt a systems-focused perspective while contributing to the health improvement and obesity prevention of PPP women.


A new cellulose-based microcarrier culturing system.
A search for new substrates to be used as microcarriers for culturing mammalian cells was carried out. Commercially available microgranular anion exchange DEAE-cellulose (DE-52 of Whatman) were investigated as microcarriers for anchorage-dependent-cells. Cells from CCL-1 mouse cell line were grown on the investigated microcarriers. Mouse interferon was successfully produced after induction with Sendai virus. Interferon yield per cell was similar to that obtained in monolayer culture.


Plasma concentrations of inhaled corticosteroids in relation to airflow obstruction in asthma.
To compare the pharmacokinetic profiles of beclometasone, budesonide, fluticasone and mometasone following inhalation in patients with asthma, and explore the relationship between lung function and plasma drug concentrations. Thirty subjects with asthma and a forced expiratory volume in 1 s (FEV(1)) ranging from 36 to 138% predicted, inhaled 800 microg beclometasone, budesonide and mometasone and 1000 microg fluticasone in random order. Plasma drug concentrations were measured over 8 h and the relationship between the area under the plasma concentration-time curve (AUC(0-8)) and lung function was modelled using linear regression. Estimated AUC(0-8) values at 50 and 100% predicted FEV(1) were compared for each drug. Pharmacokinetic profiles differed markedly between the drugs. Correlation coefficients for the relation between FEV(1)% predicted and AUC(0-8) values for beclometasone, budesonide, fluticasone and mometasone were 0.37 (P = 0.05), 0.33 (P = 0.08), 0.25 (P = 0.2) and 0.52 (P = 0.004), respectively, and estimated AUC(0-8) values were 1.3 [95% confidence interval (CI) 1.0, 1.8], 1.3 (95% CI 1.0, 1.8), 1.4 (95% CI 0.9, 2.2) and 2.2 (95% CI 1.3, 3.5) times higher for the four drugs, respectively, at 100 compared with 50% predicted FEV(1.) The higher plasma concentrations of inhaled corticosteroids in patients with a higher FEV(1)% predicted suggests that, for any given dose, these patients will be at greater risk of developing adverse systemic effects with long-term use.


Genetic organization and expression of citrate permease in lactic acid bacteria.
Citrate is present in many natural substrates, such as milk, vegetables and fruits, and its metabolism by lactic acid bacteria (LAB) plays an important role in food fermentation. The industrial importance of LAB stems mainly from their ability to convert carbohydrates into lactic acid and, in some species, like Lactococcus lactis and Leuconostoc mesenteroides, to produce C4 flavor compounds (diacetyl, acetoin) through citrate metabolism. Three types of genetic organization and gene locations, involving citrate metabolism, have been found in LAB. Citrate uptake is mediated by a citrate permease, which leads to a membrane potential upon electrogenic exchange of divalent citrate and monovalent lactate. The internal citrate is cleaved into acetate and oxaloacetate by a citrate lyase, and oxaloacetate is decarboxylated into pyruvate by an oxaloacetate decarboxylase, yielding a pH gradient through the consumption of scalar protons.


Critical evaluation of the reliability of DNA methylation probes on the Illumina MethylationEPIC BeadChip microarrays.
DNA methylation (DNAm) plays a crucial role in a number of complex diseases. However, the reliability of DNAm levels measured using Illumina arrays varies across different probes. Previous research primarily assessed probe reliability by comparing duplicate samples between the 450k-450k or 450k-EPIC platforms, with limited investigations on Illumina EPIC arrays. We conducted a comprehensive assessment of the EPIC array probe reliability using 138 duplicated blood DNAm samples generated by the Alzheimer's Disease Neuroimaging Initiative study. We introduced a novel statistical measure, the modified intraclass correlation, to better account for the disagreement in duplicate measurements. We observed higher reliability in probes with average methylation beta values of 0.2 to 0.8, and lower reliability in type I probes or those within the promoter and CpG island regions. Importantly, we found that probe reliability has significant implications in the analyses of Epigenome-wide Association Studies (EWAS). Higher reliability is associated with more consistent effect sizes in different studies, the identification of differentially methylated regions (DMRs) and methylation quantitative trait locus (mQTLs), and significant correlations with downstream gene expression. Moreover, blood DNAm measurements obtained from probes with higher reliability are more likely to show concordance with brain DNAm measurements. Our findings, which provide crucial reliable information for probes on the EPIC array, will serve as a valuable resource for future DNAm studies.


[Colles fracture and instability of wrist joint].
We reviewed 51 cases of colles fracture patients with 3-6 years follow-up and found 20 cases had dorsal carpal subluxation (DCS) in this group. Long term results were analysed and compared between the simple Colles fracture and the Colles fracture with DCS. It was shown that the remote function of the wrist in the simple Colles fracture was much more satisfactory than in that with DCS. That indicated the DCS is a very important factor to the late results of the wrist after Colles fracture. The authors pointed out that the DCS occurs frequently in the severely displaced type caused by high energy force and in the fracture associated with scapholunate dissociation. During the close reduction of the Colles fracture associated with DCS, correction of the palmar angulation and decrease of the angle of palmar tilt should be required, as well as the neutral or light dorsal flexion fixation of the wrist after reduction.


A New Method for Breath and Blood Alcohol Determination in Rats Using a Breath Alcohol Meter: An Experimental Study.
The use of police breath alcohol detectors in rat breath alcohol detection experiments has always been a challenge because of the small lung capacity and inability of rats to actively inhale. However, the method of using gas chromatography to detect blood alcohol concentration is time-consuming, complex, relatively expensive, and cannot achieve on-site detection and multi-point unlimited non-invasive detection. In this study, a laboratory method was validated for rat breath ethanol concentration (BrAC) measurement to estimate blood ethanol concentration (BAC) in rats. The rats were placed in a gas collection bottle, the breath sample was drawn out with a syringe, and injected into the mouthpiece of the breath alcohol detector through a rubber tube. The results were immediately detected and automatically converted to BAC. Male rats were randomly divided into three groups. The control group received an intraperitoneal injection of normal saline, the liver injury group received an intraperitoneal injection of 50% Carbon tetrachloride (CCL4 1 mL.kg-1), and the induction group received an intraperitoneal injection of phenobarbital sodium (75 mg.kg-1). Western blot analysis was used to detect the protein expression of CYP2E1. Similar grouping and experimental methods were used for female rats. This method was reproducible. The metabolic activity of CYP2E1 was downregulated in the injury group and upregulated in the induction group, which was consistent with the results obtained for CYP2E1 protein expression. Our results confirmed that the rat gas cylinder breath alcohol assay can be used for multiple detections with immediate and non-invasive determination of alcohol metabolizing capacity. This is important for studies that require repeated assessment of blood alcohol levels.


Development of CRISPR/Cas9 system for targeted DNA modifications and recent improvements in modification efficiency and specificity.
The targeted nuclease clustered, regularly interspaced short palindromic repeats/CRISPR-associated proteins (CRISPR/Cas) system has recently emerged as a prominent gene manipulation method. Because of its ease in programming targeted DNA/protein binding through RNA in a vast range of organisms, this prokaryotic defense system is a versatile tool with many applications in the research field as well as high potential in agricultural and clinical improvements. This review will present a brief history that led to its discovery and adaptation. We also present some of its restrictions, and modifications that have been performed to overcome such restrictions, focusing specifically on the most common CRISPR/Cas9 mediated non-homologous end joint repair. [BMB Reports 2020; 53(7): 341-348].


Lack of sensitivity of endometrial thickness in predicting the presence of an ectopic pregnancy.
The purpose of this study was to evaluate whether endometrial thickness measurements can be used to differentiate between patients with ectopic pregnancy and spontaneous abortion. Of 676 patients with clinical suspicion of ectopic pregnancy, no intrauterine pregnancy was seen in 128. Of these, 42 (33%) had ectopic pregnancy, 52 (40%) had spontaneous abortion, and 34 (27%) had intrauterine pregnancy. No significant difference was found in endometrial thickness between women with ectopic pregnancy (mean, 9.0 mm; range, 2 to 20 mm) and those with spontaneous abortion (mean, 8.4 mm; range, 2 to 18 mm). A thin endometrium seen on transvaginal sonography cannot be used to exclude the diagnosis of ectopic pregnancy.


[Determination of thiophanate-methyl and carbendazim in cucumber and soil by QuEChERS-high performance liquid chromatography-triple quadrupole tandem mass spectrometry].
A method was developed for the determination of thiophanate-methyl and carbendazim residues in cucumber and soil by using QuEChERS-high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). The residues in the samples were extracted by acetonitrile, cleaned up by developed QuEChERS method, and then analyzed by using LC-MS/MS in multiple reaction monitoring (MRM) mode via positive electrospray ionization with an Agilent ZORBAX SB-C, column (30 mm x 2.1 mm, 5 microm) as the analytical column. The recoveries of thiophanate-methyl spiked at four levels of 0.01, 0.05, 0.1 and 1.0 mg/kg were from 87.3% to 96.0% with the relative standard deviations (RSDs) of 8.0%-9.3% in cucumber, from 88.8% to 93.4% with the RSDs of 5.3%-9.9% in soil; the recoveries of carbendazim spiked at the same levels as those of thiophanate-methyl were from 87.1% to 92.3% with the RSDs of 5.2%-7.5% in cucumber, from 85.8% to 90.9% with the RSDs of 5.3%-13.2% in soil. The method is simple, rapid and characterized with acceptable sensitivity and accuracy to meet the requirements of the pesticide residue analysis. This method is applicable to confirm the residues of thiophanate-methyl and carbendazim


EpCAM expression in retinoblastoma: a novel molecular target for therapy.
This study was conducted to investigate the potential of targeting epithelial cell adhesion molecules (EpCAMs) in the treatment of retinoblastoma. It was first determined whether EpCAM is expressed in retinoblastoma and then whether EpCAM reactivity correlates with tumor aggressiveness. EpCAM reactivity was evaluated by immunohistochemistry in 43 retinoblastoma specimens from 43 patients, by using the monoclonal antibody GA733.2. The tumors were divided into two groups. There were 20 tumors with no invasion of the choroid and optic nerve (group A) and 23 tumors with invasion of the choroid, optic nerve, and orbit (group B). EpCAM reactivity was correlated with invasion and differentiation of the tumors. Among the 43 tumors, EpCAM reactivity was observed in 100% (43/43) tumors. EpCAM reactivity was significantly higher in the invasive than the noninvasive tumors (P < 0.05) and in poorly differentiated than in well-differentiated tumors (P < 0.005). Non-neoplastic retina also expressed EpCAM. The results confirm that EpCAM is vastly expressed in retinoblastoma and point to its use as a target for therapy in the future.


The Acid and/or Thermal Mediated Ring Contraction of 4H-1,2,6-Thiadiazines To Afford 1,2,5-Thiadiazoles.
A near-quantitative acid and/or thermal mediated ring contraction of 3',5'-diarylspiro(benzo[d][1,3]dioxole-2,4'-[1,2,6]thiadiazines) affords 3-aryl-4-(2-arylbenzo[d][1,3]dioxol-2-yl)-1,2,5-thiadiazoles. The reaction scope was studied providing 11 examples of this ring contraction. A double Wagner-Meerwein reaction mechanism is proposed.


Investigating 3R In Vivo Approaches for Bio-Distribution and Efficacy Evaluation of Nucleic Acid Nanocarriers: Studies on Peptide-Mimicking Ionizable Lipid.
Formulations based on ionizable amino-lipids have been put into focus as nucleic acid delivery systems. Recently, the in vitro efficacy of the lipid formulation OH4:DOPE has been explored. However, in vitro performance of nanomedicines cannot correctly predict in vivo efficacy, thereby considerably limiting pre-clinical translation. This is further exacerbated by limited access to mammalian models. The present work proposes to close this gap by investigating in vivo nucleic acid delivery within simpler models, but which still offers physiologically complex environments and also adheres to the 3R guidelines (replace/reduce/refine) to improve animal experiments. The efficacy of OH4:DOPE as a delivery system for nucleic acids is demonstrated using in vivo approaches. It is shown that the formulation is able to transfect complex tissues using the chicken chorioallantoic membrane model. The efficacy of DNA and mRNA lipoplexes is tested extensively in the zebra fish (Danio rerio) embryo which allows the screening of biodistribution and transfection efficiency. Effective transfection of blood vessel endothelial cells is seen, especially in the endocardium. Both model systems allow an efficacy screening according to the 3R guidelines bypassing the in vitro-in vivo gap. Pilot studies in mice are performed to correlate the efficacy of in vivo transfection.


Northern Ontario's Obstetrical Services in 2020: A developing rural maternity care desert.
Rural maternity care services matter. Obstetrical care in rural Canada has seen concerning trends of service closures and decreasing numbers of family physicians who predominantly provide this service. Such reductions have been shown to have a serious impact on maternal/foetal well-being. This study investigated the present state of obstetrical services in Northern Ontario, comparing results to those of the last similar survey in 1999. All 40 Northern Ontario communities with hospitals were surveyed, as were the 16 midwife practices in the region. : Of the 35 rural and 5 urban hospitals surveyed, the number not offering obstetrical care has risen from 37.5% in 1999 to 60% in 2020, with all the closures having been rural sites. There have been no re-openings of obstetrics in hospitals that did not offer obstetrics in 1999. Women in the 9 communities that had offered maternity services in 1999, but no longer do in 2020, now travel an average of over 1.5 h to access these services. In those communities that continue obstetrics, but stopped offering caesarean sections, women now travel 2.5 h for this surgery. Although the total number of general physicians remains at the 1999 level, the number offering intrapartum care has dropped by 65% in urban centres and by 49% in rural ones still providing maternity care. Like much of the rural United States, rural Northern Ontario is well on its way to becoming a maternity care desert. As proven in Southern Australia, supportive government policies and programmes should be established and education reform enacted to reverse this concerning trend.


Accelerated wound healing with combined NPWT and IPC: a case series.
Negative pressure wound therapy (NPWT) and intermittent pneumatic compression (IPC) have traditionally been used in patients with chronic complicated non-healing wounds. The aim of this study (retrospective case series) was to describe the use of NPWT in combination with IPC in patients with a relatively short history (2-6 months) of ulcers. All wounds showed improved healing during the treatment period with marked or moderate reduction in ulcer size, and granulation tissue formation was markedly stimulated. Oedema was markedly reduced due to IPC. Treatment was generally well tolerated. The results of this study indicate that combined NPWT and IPC can accelerate wound healing and reduce oedema, thus shortening the treatment period. Therefore, patients may have a shorter healing period and may avoid entering a chronic wound phase. However, controlled studies of longer duration are needed in order to show the long-term effect of a more accelerated treatment course.


State organization in neonates: developmental inconsistency indicates risk for developmental dysfunction.
Twenty-two healthy full-term infants were observed for 7 continuous hours in their homes weekly on weeks 2, 3, 4, and 5. Code recordings of their behavioral states and any mother-infant interactions were made every 10 seconds. An analysis was made of the distribution of the infant's state behaviors during the time it was left alone (mean = 279.6 minutes in 7 hours). The states were Waking Active, Quiet Alert, Fuss or Cry, Drowse or Transition, Active Sleep, and Quiet Sleep. Four state profiles were obtained for each infant, one for each week of observation; then a single quantitative measure of profile consistency over weeks was calculated. Infants with the four lowest profile consistency indices had major developmental problems between 3.5 and 30 months (p less than .001): one had aplastic anemia; a second had hypsarrhythmia, a third died of SIDS, and the fourth was hyperactive, both at home and in a testing situation. Other infants with low consistency scores showed minor developmental delays at 6 months and at 30 months. None of the infants at the upper end of the consistency continuum showed evidence of any developmental dysfunction by 30 months of age. The findings indicate that developmental inconsistency in state organization during the neonatal period is predictive of risk for later development.


A histomorphologic study of scoliosis in pinealectomized chickens.
Pinealectomy was used to induce scoliosis in Broiler chickens, and a histologic investigation of the pinealectomized chickens was performed. To investigate the incidence of scoliosis in pinealectomized Broiler chickens and to determine histologic changes in vertebrae in the pinealectomized chickens before the occurrence of a secondary vertebral wedging deformity due to scoliosis. White Leghorn chickens have previously been used as an experimental model of scoliosis, but the occurrence of scoliosis in these chickens following pinealectomy has varied in different reports and is not always high. It is accepted that the development of scoliosis has a close association with growth, but the etiology and mechanism of the disease remain unknown. Histologic findings in vertebrae after the occurrence of scoliosis include those caused by secondary changes due to mechanical compression, and no histologic data for the period before the occurrence of scoliosis are available. Study 1. A total of 100 female "Broiler" chickens were pinealectomized, and the frequency with which scoliosis occurred was investigated. Study 2. Sixty female Broiler chickens were divided into three groups: the control group (Group C, n = 20), the sham operation group (Group S, n = 20), and the pinealectomy group (Group P, n = 20). Each group was then subdivided into two groups according to the time of death: 3 days after the operation (Group 3-C, 3-S, 3-P, n = 10), and 6 days after the operation (Group 6-C, 6-S, 6-P, n = 10). Decalcified thin sagittal sections were made using a tartrate-resistant acid phosphatase (TRAP) stain. Histologic examinations of the growth plate, trabecular structure, and osteoclast number were performed. The incidence of scoliosis in the pinealectomized Broiler chickens was 93.6%. Nine of the 10 chickens in Group 6-P showed scoliosis deformity, while the presence of scoliosis was unclear in chickens in Group 3-P. The osteoclast number increased significantly in Group 3-P, compared with Groups 3-C and 3-S, and the trabecular thickness was greater in Group 3-P than in Groups 3-C and 3-S. There was no significant change in the growth plate or in other aspects of the trabecular structure, except for trabecular thickness, in any of the groups. The results show that the incidence of scoliosis using pinealectomized Broiler chickens is sufficient to study histologic changes of the vertebral body before onset of scoliosis. We found that the osteoclast number and trabecular thickness increased in pinealectomized chickens after 3 days after surgery, just before scoliosis began to develop, and that no change in the growth plate occurred. This suggests that there is no association between changes in the growth plate and the development of scoliosis. However, the change in osteoclast number may have an association with the development of scoliosis, through changes in bone modeling.


[Neurological involvement in Wegener's granulomatosis: report of one case].
Wegener's granulomatosis is a systemic necrotizing vasculitis that affects medium size and small vessels. Neurological involvement occurs in 22% to 54% of patients, mainly in the form of mononeuritis multiplex. Central nervous system involvement is reported in only 2% to 8% of the cases. We report a 42-year-old male who presented with headache, diplopia, third and sixth cranial nerve palsies and left eye amaurosis associated to mass located in the Meckel cavum and diffuse meningeal involvement. A biopsy of the mass disclosed a chronic granulomatous necrotizing inflammation with Langhans giant cells. A chest CAT scan showed three cavitated lung nodules and ANCA antibodies were positive in a titer of 1:80. Treatment with steroid and cyclophosphamide was started and cranial nerve palsies resolved and the number and size of lung nodules decreased. The patient was lost from follow up.


Does the relationship of ambulatory blood pressure to position and location vary by age, sex, race/ethnicity, or body mass index?
The effects of position and location on ambulatory blood pressure, and the variability in these effects across individuals was examined. The extent to which the variability among individuals could be predicted by age, sex, race/ethnicity, and body mass was also assessed. The data include 24-hour ambulatory blood pressure recordings of 246 subjects from an ongoing worksite study. A random coefficients model yielded estimates of within-person and between-person effects. The position and location of individuals significantly affect their ambulatory blood pressure. As position changes from reclining to sitting to standing, blood pressure increases, after controlling for location. Likewise, blood pressure is typically higher at work than at home, controlling for position. The effects on blood pressure of both position and location vary considerably across persons. Interpersonal variability, measured by the standard deviation, is typically 30-75% as large as the variability in mean levels of blood pressure. There is also an interaction effect of position and location: the difference in blood pressure between standing and sitting down at work is not the same as the corresponding difference at home. Age, sex, race/ethnicity, and body mass index (BMI) predict 17% of the interpersonal variability in average systolic blood pressure while sitting at home, and 6% in diastolic blood pressure. The analysis of whether the effects of position or location vary by age, sex, race/ethnicity or BMI shows that the difference between work and home blood pressures is not significantly related to any of these four factors. However, the difference between awake and sleep diastolic blood pressures can be predicted, in part, by age and perhaps race/ethnicity. As age increases, the drop in diastolic blood pressure during sleep is attenuated. Hispanics also appear to experience a smaller drop in blood pressure during sleep. The drop in blood pressure associated with lying down (while awake) is similarly related to age and race/ethnicity. The increase in blood pressure associated with standing (vs. sitting) while at work is also attenuated in older individuals. Although significant interaction effects were demonstrated, these four major risk factors for hypertension predicted only small percentages of the interpersonal variability in the effects of position and location on blood pressure. Am. J. Hum. Biol. 10:459-470, 1998. © 1998 Wiley-Liss, Inc.


Estimating mono- and bi-phasic regression parameters using a mixture piecewise linear Bayesian hierarchical model.
The dynamics of tumor burden, secreted proteins or other biomarkers over time, is often used to evaluate the effectiveness of therapy and to predict outcomes for patients. Many methods have been proposed to investigate longitudinal trends to better characterize patients and to understand disease progression. However, most approaches assume a homogeneous patient population and a uniform response trajectory over time and across patients. Here, we present a mixture piecewise linear Bayesian hierarchical model, which takes into account both population heterogeneity and nonlinear relationships between biomarkers and time. Simulation results show that our method was able to classify subjects according to their patterns of treatment response with greater than 80% accuracy in the three scenarios tested. We then applied our model to a large randomized controlled phase III clinical trial of multiple myeloma patients. Analysis results suggest that the longitudinal tumor burden trajectories in multiple myeloma patients are heterogeneous and nonlinear, even among patients assigned to the same treatment cohort. In addition, between cohorts, there are distinct differences in terms of the regression parameters and the distributions among categories in the mixture. Those results imply that longitudinal data from clinical trials may harbor unobserved subgroups and nonlinear relationships; accounting for both may be important for analyzing longitudinal data.


Purification of ribosomes from human cell lines.
Highly conserved during evolution, the ribosome is the central effector of protein synthesis. In mammalian cells, the ribosome is a macromolecular complex composed of four different ribosomal RNAs (rRNA) and about 80 ribosomal proteins. Requiring more than 200 factors, ribosome biogenesis is a highly complex process that takes place mainly within the nucleoli of eukaryotic cells. Crystallographic data suggest that the ribosome is a ribozyme, in which the rRNA catalyses the peptide bond formation and ensures quality control of the translation. Ribosomal proteins are involved in this molecular mechanism; nonetheless, their role is still not fully characterized. Recent studies suggest that ribosomes themselves and/or the mechanisms underlying their synthesis, processing, and assembly play a key role in the establishment and progression of several human pathologies. The protocol described here is simple, efficient, and robust, and allows one to purify high-quality ribosomes from human cultured cell lines. Ribosomes purified with this protocol are adequate for most of the subsequent analyses of their RNA and protein content.


Saccharide orientation at the cell surface affects glycolipid receptor function.
Three allelic variants of P-pilus-associated G-adhesins (lectins) with different cell-binding properties were recently described. Here we have analyzed Escherichia coli HB101 strains expressing the recombinant G-adhesin variants for their ability to agglutinate erythrocytes from various species as this relates to the glycosphingolipid (GSL) composition in the erythrocyte membranes. All three variants exhibit similar specificities for the globo-series GSLs affixed to artificial surfaces. However, only the PapGJ96 adhesin induces agglutination of erythrocytes having globotriaosylceramide (GbO3) [Gal(alpha 1-4)LacCer] as the major GSL. Furthermore, only PapGAD110 induces strong agglutination of erythrocytes having globotetraosylceramide (GbO4) [GalNAc(beta 1-3)Gal(alpha 1-4)LacCer] as the major GSL, while PrsGJ96 alone agglutinates those containing globopentaosylceramide (GbO5) [GalNAc(alpha 1-3)GalNAc(beta 1-3)Gal(alpha 1-4)LacCer]. Molecular modeling of these globo-GSLs demonstrates different saccharide orientations to the membrane surface for these isoreceptors. We suggest that the differential binding of the three G-adhesin variants results from differences in epitope presentation at the membrane among these globo-GSLs.


Measuring User Compliance and Cost Effectiveness of Safe Drinking Water Programs: A Cluster-Randomized Study of Household Ultraviolet Disinfection in Rural Mexico.
Low adoption and compliance levels for household water treatment and safe storage (HWTS) technologies have made it challenging for these systems to achieve measurable health benefits in the developing world. User compliance remains an inconsistently defined and poorly understood feature of HWTS programs. In this article, we develop a comprehensive approach to understanding HWTS compliance. First, our Safe Drinking Water Compliance Framework disaggregates and measures the components of compliance from initial adoption of the HWTS to exclusive consumption of treated water. We apply this framework to an ultraviolet (UV)-based safe water system in a cluster-randomized controlled trial in rural Mexico. Second, we evaluate a no-frills (or "Basic") variant of the program as well as an improved (or "Enhanced") variant, to test if subtle changes in the user interface of HWTS programs could improve compliance. Finally, we perform a full-cost analysis of both variants to assess their cost effectiveness (CE) in achieving compliance. We define "compliance" strictly as the habit of consuming safe water. We find that compliance was significantly higher in the groups where the UV program variants were rolled out than in the control groups. The Enhanced variant performed better immediately postintervention than the Basic, but compliance (and thus CE) degraded with time such that no effective difference remained between the two versions of the program.


Ab initio study on the molecular structure of the naphthalene metabolite, trans-1,2-dihydroxy-1,2-dihydronaphthalene.
The molecular geometries of three conformations of trans-1,2-dihydroxy-1,2-dihydronaphthalene have been refined by an ab initio gradient procedure at the 4-21G level to determine the effect of dihydrodiol conformation on arene structure. The preferred conformation is an equatorial form similar to the most stable conformation of ethylene glycol. All the structures investigated have similar arene geometries. The effect of the various conformations on metabolism of dihydrodiols to dihydrodiol epoxides is considered.


Assessment of the reproducibility of alginate encapsulation of pancreatic islets using the MTT colorimetric assay.
Radioisotope diffusion experiments demonstrate that alginate/polyaminoacid encapsulation can prevent antibody and cytotoxic cell contact in vitro. The unpredictable outcome of xenotransplantation of encapsulated islets may reflect incomplete encapsulation. We have assessed a cytotoxic/MTT (tetrazolium) assay to test antibody permeability of capsules. Samples of free porcine islet tissue, and islet tissue encapsulated in alginate/poly-L-lysine/alginate microspheres were incubated with fresh autologous pig serum or normal human serum overnight. Cell metabolism was assessed by the MTT assay. Data from eight experiments (10 replicates/experiment) were analyzed using the Mann-Whitney U-test. Values were deemed significant when p < 0.05. Free islets cultured in human serum showed a significant reduction in metabolism when compared with islets cultured in pig serum: percentage reduction 52 +/- 23% (mean +/- SD). The differences in formazan production were significant in all experiments (p < 0.05). Alginate encapsulation of islets or removal of xenoreactive antibodies in human serum by adsorption was shown to prevent the effects of complement-mediated lysis. However, in one of the eight experiments, there was a significant reduction in islet metabolism after exposure of encapsulated porcine islets to human serum. In conclusion, it has been shown that alginate encapsulation can prevent complement-mediated lysis. However, the encapsulation process employed was imperfect and did not prevent complement-mediated lysis of porcine islets in all experiments. The cytotoxicity/MTT assay allows investigation of the permeability of capsules to serum antibodies and could be performed to determine the viability of the islets and the integrity of microcapsules prior to transplantation.


Acinar cells are target cells for androgens in mouse submandibular glands.
The variable coding sequence (VCS) multigene family encodes diverse salivary proteins, such as the SMR1 prohormone and the PR-VB1 proline-rich protein in the rat. In situ hybridization was used to study the cell-specific expression of two new mouse VCS genes, Vcs1 and Vcs2. We show that the Vcs1 transcripts, which code for a proline-rich protein, MSG1, are highly abundant in male and female parotid glands, in which they are specifically detected in acinar cells. No expression was seen in the submandibular or sublingual glands. In contrast, Vcs2 transcripts were found only in the acinar cells of the submandibular glands (SMGs) of male mice, in which they are expressed in response to androgens. Expression was found to be heterogeneous within acinar structures. No Vcs2 transcripts were detected in the SMGs of females or castrated males by Northern blot, RNase protection, or in situ hybridization. Androgen administration to females or castrated males induced expression at a level comparable to that of intact males. The Vcs2 gene is the first example of a mouse androgen-regulated gene that is expressed in SMG acinar cells. This result, in addition to our previous observation on SMR1 expression in rats, demonstrates that both acinar cells and granular convoluted tubule (GCT) cells are target cells for androgen action in rodent SMG.


Expression of the translocator protein (TSPO) from Pseudomonas fluorescens Pf0-1 requires the stress regulatory sigma factors AlgU and RpoH.
The translocator protein (TSPO), previously designated as peripheral-type benzodiazepine receptor, is an evolutionary conserved protein that is found in many Eukarya, Archae, and Bacteria, in which it plays several important functions including for example membrane biogenesis, signaling, and stress response. A tspo homolog gene has been identified in several members of the Pseudomonas genus, among which the soil bacterium P. fluorescens Pf0-1. In this bacterium, the tspo gene is located in the vicinity of a putative hybrid histidine kinase-encoding gene. Since tspo has been involved in water stress related response in plants, we explored the effects of hyperosmolarity and temperature on P. fluorescens Pf0-1 tspo expression using a strategy based on lux-reporter fusions. We show that the two genes Pfl01_2810 and tspo are co-transcribed forming a transcription unit. The expression of this operon is growth phase-dependent and is increased in response to high concentrations of NaCl, sucrose and to a D-cycloserine treatment, which are conditions leading to activity of the major cell wall stress responsive extracytoplasmic sigma factor AlgU. Interestingly, the promoter region activity is strongly lowered in a P. aeruginosa algU mutant, suggesting that AlgU may be involved at least partly in the molecular mechanism leading to Pfl01_2810-tspo expression. In silico analysis of this promoter region failed to detect an AlgU consensus binding site; however, a putative binding site for the heat shock response RpoH sigma factor was detected. Accordingly, the promoter activity of the region containing this sequence is increased in response to high growth temperature and slightly lowered in a P. aeruginosa rpoH mutant strain. Taken together, our data suggest that P. fluorescens tspo gene may belong at least partly to the cell wall stress response.


Synthesis and Characterization of Biodegradable Lignin Nanoparticles with Tunable Surface Properties.
Lignin nanoparticles can serve as biodegradable carriers of biocidal actives with minimal environmental footprint. Here we describe the colloidal synthesis and interfacial design of nanoparticles with tunable surface properties using two different lignin precursors, Kraft (Indulin AT) lignin and Organosolv (high-purity lignin). The green synthesis process is based on flash precipitation of dissolved lignin polymer, which enabled the formation of nanoparticles in the size range of 45-250 nm. The size evolution of the two types of lignin particles is fitted on the basis of modified diffusive growth kinetics and mass balance dependencies. The surface properties of the nanoparticles are fine-tuned by coating them with a cationic polyelectrolyte, poly(diallyldimethylammonium chloride). We analyze how the colloidal stability and dispersion properties of these two types of nanoparticles vary as a function of pH and salinities. The data show that the properties of the nanoparticles are governed by the type of lignin used and the presence of polyelectrolyte surface coating. The coating allows the control of the nanoparticles' surface charge and the extension of their stability into strongly basic regimes, facilitating their potential application at extreme pH conditions.


Altered Macular Vasculature in Migraine Patients without Aura: Is It Associated with Ocular Vasculature and White Matter Hyperintensities?
We aimed to determine the alterations in macular and optic nerve vasculature in patients with migraine without aura using optical coherence tomography-angiography (OCTA). We also aimed to determine whether there were clinical differences and alterations in ocular structures in migraine cases with white matter hyperintensities (WMH) using magnetic resonance imaging (MRI). Materials and Methods. The study group comprised patients with migraine without aura and age- and sex-matched healthy controls. Detailed histories of the patients with migraine were recorded including the disease duration, number of attacks in the last month, and attack durations. Visual evoked potentials (VEP) were recorded in all migraine patients. The migraine disability assessment (MIDAS) questionnaire was administered to all patients. The patients were divided into two groups as migraine with WMHs and migraine without WMHs. All subjects underwent a complete neurological and ophthalmological examination. Only the right eyes of the patients were included in the study. Retinal imaging was performed using OCT and OCTA. A total of 66 migraine patients (29 with WMH and 37 without WMH) and 43 healthy controls were included in this study. Among the migraine patients, disease duration, attack frequency in the last month, attack durations, and the visual analogue scale (VAS), MIDAS, and VEP scores were all similar between those with and without WMHs. There was no significant difference between the groups regarding the ganglion cell complex, foveal, and retinal nerve fiber layer thicknesses. The superficial or deep vascular perfusion densities of the optic disc were also similar between the groups. The foveal avascular zone (FAZ) was significantly larger (P=0.034), and both superficial and deep macular vascular densities were significantly lower in the migraine groups compared with the healthy controls (P=0.001). There was no significant difference concerning the FAZ size or vascular densities between the migraine groups with and without WMHs. In the correlation analysis performed between the migraine patients, the FAZ size was correlated with age and VAS and MIDAS scores while both superficial and deep macular vascular densities were negatively correlated with age and VAS and MIDAS scores. We suggest that for not only migraine with aura but also migraine without aura, neurovascular structures play an important role in pathogenesis, and novel studies are warranted to elucidate the alterations in these and determine the significance of WMHs in these patient groups.


Values of urine specific gravity for thoroughbred horses treated with furosemide prior to racing compared with untreated horses.
The distribution of specific gravity values for 2,599 urine samples collected from racing Thoroughbred horses that were known to have received furosemide prior to racing was compared with that for 1,669 urine samples from racing Thoroughbred horses that reportedly had not received furosemide. Values of specific gravity for furosemide-treated horses were significantly lower (P < 0.001) than those for horses that had not received furosemide, and the proportion of horses with urine specific gravity either <1.010 or <1.012 was significantly greater (P < 0.001) among the furosemide-treated horses. These data indicate that evaluation of urine specific gravity would be a useful component of drug testing programs for regulation of furosemide use.


Elaborate tree-like Cu-Ag clusters from green electrodeposition for efficiently electrocatalyzing CO2 conversion into syngas.
The electrocatalytic carbon dioxide reduction (CO2RR) is one of the emerging technologies that can effectively transform carbon dioxide (CO2) into valuable products. Electrocatalysts deriving from green synthesis methods will significantly help to establish a new green carbon cycle. Herein, a green electrodeposition method without additional reducing agents was used to synthesize Cu-Ag bimetallic catalysts, and it is shown that the combination of Cu and Ag obviously affects the morphology of the Cu-Ag catalysts, resulting in the formation of elaborate tree-like Cu-Ag clusters. An as-deposited Cu-Ag/carbon fiber (Cu-Ag/CF) catalyst exhibits high activity, selectivity and stability toward the CO2RR; in particular, the elaborate dendritic Cu-Ag/CF can efficiently reduce CO2 to syngas with high selectivity (Faradaic efficiency (FE) > 95%) at a low onset potential (-0.5 V). This work provides a rational strategy to overcome the significantly different reaction capacities during the reduction of Ag+ and Cu2+, leading to the formation of a controlled morphology of Cu-Ag, which is favourable for the design and development of highly efficient Cu or Ag catalysts via green methods for electrocatalyzing the CO2RR.


A novel method for localizing reporter fluorescent beads near the cell culture surface for traction force microscopy.
PA gels have long been used as a platform to study cell traction forces due to ease of fabrication and the ability to tune their elastic properties. When the substrate is coated with an extracellular matrix protein, cells adhere to the gel and apply forces, causing the gel to deform. The deformation depends on the cell traction and the elastic properties of the gel. If the deformation field of the surface is known, surface traction can be calculated using elasticity theory. Gel deformation is commonly measured by embedding fluorescent marker beads uniformly into the gel. The probes displace as the gel deforms. The probes near the surface of the gel are tracked. The displacements reported by these probes are considered as surface displacements. Their depths from the surface are ignored. This assumption introduces error in traction force evaluations. For precise measurement of cell forces, it is critical for the location of the beads to be known. We have developed a technique that utilizes simple chemistry to confine fluorescent marker beads, 0.1 and 1 µm in diameter, in PA gels, within 1.6 μm of the surface. We coat a coverslip with poly-D-lysine (PDL) and fluorescent beads. PA gel solution is then sandwiched between the coverslip and an adherent surface. The fluorescent beads transfer to the gel solution during curing. After polymerization, the PA gel contains fluorescent beads on a plane close to the gel surface.


The interaction of thrombin with blood platelets.
Thrombin is a potent agonist of platelets. In the current article, the research on the interaction of thrombin with blood platelets is reviewed starting with the first studies demonstrating the direct action of thrombin on platelets and ending with an analysis of the importance of the protease-activated receptors (PARs) and the GpIb complex. The antithrombin activity of platelets is discussed in terms of the binding of thrombin to receptor(s) on the platelet surface. Evaluation of the PAR receptors and the GpIb supports a model where thrombin binds to the GpIb receptor prior to the proteolysis of the PAR receptor(s). Thus, the maximal hemostatic response requires both PAR receptors and the GpIb receptors.


Benign nontraumatic inflammatory stricture of mid portion of common bile duct mimicking malignant tumor: Report of two cases.
Benign nontraumatic inflammatory stricture of the common bile duct (CBD) may result in obstructive jaundice, which can be misdiagnosed as a malignant tumor of the CBD preoperatively. Two cases with strictures of the mid portion of the common bile duct presenting with obstructive jaundice are reported herein. Preoperative radiological studies prompted us to confidently make the diagnosis of cholangiocarcinoma. However, the postoperative diagnosis on histological examination of the resected lesions was chronic inflammation and fibrosis. The complications of chronic duodenal ulcer are considered as the etiology of these two disorders.


Evidence for an African cluster of human head and body lice with variable colors and interbreeding of lice between continents.
Human head lice and body lice have been classified based on phenotypic characteristics, including geographical source, ecotype (preferred egg laying site hair or clothes), shape and color. More recently, genotypic studies have been based on mitochondrial genes, nuclear genes and intergenic spacers. Mitochondrial genetic analysis reclassified lice into three genotypes (A, B and C). However, no previous study has attempted to correlate both genotypic and phenotypic data. Lice were collected in four African countries: Senegal, Burundi, Rwanda and Ethiopia and were photographed to compare their colors. The Multi-Spacer-Typing (MST) method was used to genotype lice belonging to the worldwide Clade A, allowing a comparison of phenotypic and genotypic data. No congruence between louse color and genotype has been identified. Phylogenetic analysis of the spacer PM2, performed including lice from other sources, showed the existence of an African cluster of human lice. However, the analysis of other spacers suggested that lice from different areas are interbreeding. We identified two geotypes of Clade A head and body lice including one that is specifically African, that can be either black or grey and can live on the head or in clothing. We also hypothesized that lice from different areas are interbreeding.


The syndromes of isolated gonadotropin deficiency.
Six theoretically possible syndromes of IGD are shown in Table 1. 1) IBGD is well-substantiated both in males and in females, and appears to be either of pituitary or more frequently of nonpituitary origin. 2) An example of isolated FSH deficiency has been described. The defect appears to reside at the pituitary level and may be localized to the FSH beta subunit. Recently a male patient has been studied with isolated FSH deficiency and a concordant testicular picture viz germinal cell aplasia. However, the syndrome is complicated by an associated chromosomal abnormality (XO/XXY/XY) whose significance is unclear. 3) Several examples of isolated hLH deficiency have been described. Several questions remain about the exact nature of the defect in some of the published reports of this syndrome.


Challenges Toward the Identification of Predictive Markers for Human Mesenchymal Stromal Cells Chondrogenic Potential.
Human bone marrow derived mesenchymal stromal cells (BMSCs) represent a putative cell source candidate for tissue engineering-based strategies to repair cartilage and bone. However, traditional isolation of BMSCs by adhesion to plastic leads to very heterogeneous cell populations, accounting for high variability of chondrogenic differentiation outcome, both across donors and across clonally derived strains. Identification of putative surface markers able to select BMSC subpopulations with higher chondrogenic capacity (CC) and reduced variance in chondrogenic differentiation could aid the development of BMSC-based cartilage and bone regeneration approaches. With the goal to identify predictive markers for chondrogenic BMSC populations, we assessed the gene expression profile of single cell-derived clones with high and low CC. While a clustering between high and low CC clones was observed for one donor, donor-to-donor variability hampered the possibility to achieve conclusive results when different donors were considered. Nevertheless, increased NCAM1/CD56 expression correlated in clones derived from one donor with higher CC, the same trend was observed for three additional donors (even if no significance was achieved). Enriching multiclonal BMSCs for CD56+ expression led to an increase in CC, though still highly affected by donor-to-donor variability. Our study finally suggests that definition of predictive marker(s) for BMSCs chondrogenesis is challenged by the large donor heterogeneity of these cells, and by the high complexity and plasticity of the BMSCs system. Multiple pathways and external parameters may be indeed involved in determining the chondrogenic potential of BMSCs, making the identification of putative markers still an open issue. Stem Cells Translational Medicine 2019;8:194&11.


Postoperative management of the patient undergoing pulmonary endarterectomy.
The postoperative care of the patient undergoing pulmonary endarterectomy presents challenges that occur not only with other types of cardiac surgery but also with significant respiratory system changes related to alterations in pulmonary blood flow. Postoperative mortality associated with this procedure has declined substantially over the years as a consequence of improved evaluative procedures and selective surgical referral, advances in surgical technique, and an understanding of the unique postoperative complications that may occur. However, postoperative acute lung injury and residual pulmonary hypertension continue to represent major causes of mortality associated with this procedure and represent areas where additional investigative efforts are necessary. Here we describe the unique hemodynamic and respiratory changes that occur in the postoperative pulmonary endarterectomy patient and an evidence-based approach to their optimal management.


Comparative short-term evaluation of penfluridol and trifluoperazine in chronic schizophrenia.
A double blind comparative study was conducted to evaluate the efficacy and safety of penfluridol and trifluoperazine in patients of chronic schizophrenia. Penfluridol was administered once weekly while trifluoperazine was administered twice daily by preparing identical capsules. The data revealed that both the compounds were similarly effective in maintaining control of symptoms of chronic schizophrenia. However, penfluridol has a definite advantage over trifluoperazine since it is administered once a week instead of twice a day.


Human biomonitoring of chromium and nickel from an experimental exposure to manual metal arc welding fumes of low and high alloyed steel.
The uptake and elimination of metals from welding fumes is currently not fully understood. In the Aachen Workplace Simulation Laboratory (AWSL) it is possible to investigate the impact of welding fumes on human subjects under controlled exposure conditions. In this study, the uptake and elimination of chromium or chromium (VI) respectively as well as nickel was studied in subjects after exposure to the emissions of a manual metal arc welding process using low or high alloyed steel. In this present study 12 healthy male non-smokers, who never worked as welders before, were exposed for 6h to welding fumes of a manual metal arc welding process. In a three-fold crossover study design, subjects were exposed in randomized order to either clean air, emissions from welding low alloyed steel, and emissions from welding high alloyed steel. Particle mass concentration of the exposure aerosol was 2.5mg m(-3). The content of chromium and nickel in the air was determined by analysing air filter samples on a high emission scenario. Urine analysis for chromium and nickel was performed before and after exposure using methods of human biomonitoring. There were significantly elevated chromium levels after exposure to welding fumes from high alloyed steel compared to urinary chromium levels before exposure to high alloyed welding fumes, as well as compared to the other exposure scenarios. The mean values increased from 0.27 µg l(-1) to 18.62 µg l(-1). The results were in good agreement with already existing correlations between external and internal exposure (German exposure equivalent for carcinogenic working materials EKA). The variability of urinary chromium levels was high. For urinary nickel no significant changes could be detected at all. Six-hour exposure to 2.5mg m(-3) high alloyed manual metal arc welding fumes lead to elevated urinary chromium levels far higher (7.11-34.16 µg l(-1)) than the German biological exposure reference value (BAR) of 0.6 µg l(-1) directly after exposure. On the other hand mean urinary nickel concentrations slightly increased, but did not exceed background levels due to lower bioavailability. We could underline with our single exposure experiment that a welding work related chromium exposure can be measured immediately after the work shift, while the same is not possible for nickel exposure due to lower nickel bioavailability. The data provide useful information for real occupational welding work places.


Combined alizarin red-reticulum stain for tissue localization of calcium deposits.
A method combining alizarin red and a modified silver stain for reticulum fibers in tissue sections is described. The method allows precise localization of calcium deposits and crystals in relation to epithelial and interstitial connective tissue elements. The deposits and their spatial relationships are clearly discernible by light microscopy, especially with polarization. The method is particularly useful for investigating calculogenesis and may prove to be of value in the study of the mechanism and evolution of pathologic calcification in various organs.


Serial measurement of soluble interleukin 2 receptor levels: an early indicator of treatment response for Lyme disease.
Detection of antibodies produced in response to infection with Borrelia burgdorferi provides a valuable aid for diagnosing Lyme disease. However, anti-Borrelial antibody titers are of little value in determining treatment success or providing evidence of persistent infection as levels of specific antibodies can remain elevated even after successful treatment. Pretreatment and posttreatment measurement of soluble interleukin 2 receptor (sIL-2R) levels was evaluated for use in predicting treatment response in Lyme disease. Results indicate that serial measurement of serum sIL-2R levels can provide an early indicator of response to treatment and outcome.


Status report -- Childhood overweight and obesity in Canada: an integrative assessment.
Obesity is a complex risk factor for chronic disease that is associated with a number of socioecological determinants. In this status report, we provide an overview of the socioecological framework that is now guiding our ongoing surveillance efforts in the area of childhood overweight and obesity. This framework considers individual risk and protective factors (sociodemographic, lifestyle, psychosocial and early-life) through the lens of the life stage, levels of influence and environments in which these factors play a role. Using data from the Canadian Community Health Survey and the Canadian Health Measures Survey, univariate and bivariate analyses were used to report on behavioural, psychosocial, and early life factors associated with excess weight among Canadian children. Estimates of early-life (e.g. breastfeeding), behavioural (e.g. physical activity), and psychosocial factors (e.g. sense of community) are presented as they relate to age group, sex, income adequacy and weight status. Building upon our recent reporting on trends in and sociodemographic factors associated with childhood obesity in Canada, this work illustrates the remaining risk and protective factors shown in our surveillance framework. This analysis supports the shift towards a holistic appraisal of determinants related to healthy weights.


Carotid artery disease: stenting vs endarterectomy.
Several multicentre, randomized trials have validated the efficacy of carotid endarterectomy (CEA). Comparative randomized trials are also currently developing insight into the role of carotid angioplasty and stenting (CAS), and identifying factors for optimal patient selection. Although these interventions are aimed at embolic stroke prevention, anaesthetic management might prevent the subset of strokes that are haemodynamic in nature by maintaining tight physiological control. The perioperative risk of myocardial events is increased in this population. Hence, preoperative attention to cardiovascular disease, hypertension, renal insufficiency, and diabetes mellitus might reduce neurological and cardiovascular complications. During carotid artery cross-clamping, the risk of cerebral ischaemia can be decreased by maintaining normal to high perfusion pressure. Although there is no demonstrable advantage of a specific anaesthetic technique for patients undergoing CEA, it is imperative that cerebral blood flow is optimized, that there is minimal cardiac stress, and that anaesthetic recovery is rapid. Carotid angioplasty and stenting is performed under light sedation with antithrombotic therapy and vigilance for bradycardia and hypotension. Tight haemodynamic control remains a priority in the immediate postoperative period for both interventions.


Phospholamban as a crucial determinant of the inotropic response of human pluripotent stem cell-derived ventricular cardiomyocytes and engineered 3-dimensional tissue constructs.
Human (h) embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) serve as a potential unlimited ex vivo source of cardiomyocytes (CMs). However, a well-accepted roadblock has been their immature phenotype. hESC/iPSC-derived ventricular (v) CMs and their engineered cardiac microtissues (hvCMTs) similarly displayed positive chronotropic but null inotropic responses to β-adrenergic stimulation. Given that phospholamban (PLB) is robustly present in adult but poorly expressed in hESC/iPSC-vCMs and its defined biological role in β-adrenergic signaling, we investigated the functional consequences of PLB expression in hESC/iPSC-vCMs and hvCMTs. First, we confirmed that PLB protein was differentially expressed in hESC (HES2, H9)- and iPSC-derived and adult vCMs. We then transduced hES2-vCMs with the recombinant adenoviruses (Ad) Ad-PLB or Ad-S16E-PLB to overexpress wild-type PLB or the pseudophosphorylated point-mutated variant, respectively. As anticipated from the inhibitory effect of unphosphorylated PLB on sarco/endoplasmic reticulum Ca2+-ATPase, Ad-PLB transduction significantly attenuated electrically evoked Ca2+ transient amplitude and prolonged the 50% decay time. Importantly, Ad-PLB-transduced hES2-vCMs uniquely responded to isoproterenol. Ad-S16E-PLB-transduced hES2-vCMs displayed an intermediate phenotype. The same trends were observed with H9- and iPSC-vCMs. Directionally, similar results were also seen with Ad-PLB-transduced and Ad-S16E-transduced hvCMTs. However, Ad-PLB altered neither the global transcriptome nor ICa,L, implicating a PLB-specific effect. Engineered upregulation of PLB expression in hESC/iPSC-vCMs restores a positive inotropic response to β-adrenergic stimulation. These results not only provide a better mechanistic understanding of the immaturity of hESC/iPSC-vCMs but will also lead to improved disease models and transplantable prototypes with adult-like physiological responses.


THE MANAGEMENT OF AN ORAL ANAPLASTIC SARCOMA IN A PYGMY HIPPOPOTAMUS (CHOEROPSIS LIBERIENSIS) USING INTRALESIONAL CHEMOTHERAPY.
An adult female captive pygmy hippopotamus (Choeropsis liberiensis) was diagnosed with an oral anaplastic sarcoma. The tumor was surgically debulked and intralesional chemotherapy with mitomycin C (0.4 mg/cm3 of tumor) and cisplatin (1 mg/cm3 of tumor) was administered. Chemotherapeutic treatment proved difficult due to the risks of repeated anesthetics and unknown drug efficacies. Marked proliferation of the mass was observed during estrus, and chemotherapy was repeated as an experimental treatment to slow tumor progression in order for the animal to remain in the species breeding program. Tumor proliferation was detected during the first trimester of pregnancy; however, in the lactation period, the mass became quiescent. No adverse reactions to chemotherapeutic drugs were observed and the animal continues to be monitored for tumor progression. This is the first report of an anaplastic sarcoma and of chemotherapy use in a pygmy hippopotamus and it highlights logistical considerations for treating neoplasia in this species.


Combining Intra- and Interindividual Approaches in Epistemic Beliefs Research.
We combined inter- and intraindividual approaches to investigate university students' biology- and psychology-specific specific epistemic beliefs (beliefs about the nature and structure of knowledge). We expected that university students would perceive the discipline of biology as more absolute and less multiplistic than the discipline of psychology (intraindividual perspective). Furthermore, we expected students from so-called "hard" disciplines to perceive biology as more absolute and less multiplistic than students from soft disciplines (interindividual perspective). Finally, we expected that students from hard disciplines, compared to their peers from soft disciplines, would perceive stronger differences between biology and psychology (combined perspective). Hypotheses were tested, using Bayes factors, in N = 938 university students from a multitude of disciplines. Results revealed that university students perceive biology as considerably more absolute and less multiplistic compared to psychology. However, the findings also suggest that there are no strong interindividual differences between students from hard and soft disciplines regarding the perception of biology. Finally, results revealed that students enrolled in harder disciplines perceive a slightly stronger difference between biology and psychology. In sum, intraindividual effects were considerably stronger, which elicits doubt that students from hard disciplines espouse a fundamentally different set of epistemic beliefs than their peers from soft disciplines.


Osteosarcoma of the uterine cervix associated with hyperplastic and atypical mesonephric rests.
The authors describe a unique case of osteosarcoma associated with atypical mesonephric rests occurring in the right lateral wall of the uterine cervix. The tumor was examined histologically, cytologically, immunohistochemically, and ultrastructurally and was compared with another osteosarcoma that filled an entire uterine cavity. Comparison with other neoplasms of the uterine cervix indicates that the lesion should be classified separately. Previously reported neoplasms associated with mesonephric rests within the cervix are also reviewed.


Physiological aspects of the thyroid trapping function and its suppression in iodine deficiency using 99mTc pertechnetate.
In an area of iodine deficiency, we investigated 190 individuals with and without euthyroid endemic goitre, who had a normal TSH response after TRH and an entirely homogeneous thyroid scintigram before and under suppression. In these subjects, the thyroid uptake of 99mTc pertechnetate, as a measure of the iodide trapping function, was determined before (TcUb) and under suppression (TcUs), using quantitatively evaluated scintigraphy. In this control group of individuals, without evidence of autonomy, the reference ranges of TcUb and TcUs were determined. The upper limit of the reference range for TcUb was 7.4% of the tracer activity injected, and for TcUs 1.6%. The reference range of TcUs is to be used to detect accurately thyroid autonomy in vivo. In addition, factors affecting the thyroid trapping function were investigated. With decreased iodine supply, trapping before suppression was increased, compensating for iodine deficiency. The effect of TSH on the trapping function was secondary, indicating that, to a considerable degree, the follicular cells adapt their iodide trapping to the iodine supply. The trapping before and under suppression increased with the estimated thyroid weight. delta TSH after TRH stimulation measured before suppression correlated inversely with the trapping under suppression. The two latter observations suggest that there is a continuum between low and increased levels of the TSH-independent thyroid function, even among these selected individuals without primary evidence of autonomous tissue. A correlation of the trapping function with sex, oestrogen treatment, and goitre type was not demonstrable. Age was found to have a small influence. Except for iodine contamination, the factors affecting the pertechnetate uptake of the thyroid, can be neglected under routine conditions.


Enhancement of human natural cell-mediated cytotoxicity by interferon.
The effect of exogenous Namalva interferon (IF) on the natural killer (NK) cell activity of human blood lymphocytes was examined against 5 target cell lines (K562, CCRF/CEM, Molt 4, Raji and Bri8) using the 51Cr-release assay. Addition of IF to the test significantly increased the cytotoxicity, though not as much as when effector cells were treated with IF before the test. Augmentation of cytotoxicity was evident after only 1 h pretreatment and was maximal by 6 h. The rate of lysis of susceptible targets by IF-treated effectors markedly exceeded that by their untreated counterparts. Separation of lymphocyte subpopulations (by SRBC-rosette sedimentation and nylon-fibre column filtration) demonstrated that the activities of IF-stimulated and unstimulated cells were similarly distributed, suggesting that the major effect of IF is enhancement of the activity of pre-existing NK cells rather than generation of new populations of effectors. Target cell lines with high and low susceptibility to NK cells showed increased cytotoxicity by IF-treated effector cells. These findings may be relevant to the current discussion of the role of NK cells in immunosurveillance against neoplasia.


Progress and challenges in studies of the evolution of development.
Plant evolutionary developmental genetics (EDG) has made considerable progress over the last decade. This is in part due to the accumulation of large amounts of sequence data that have provided robust organismal phylogenies and, increasingly, broad assessments of molecular evolution. Attempts to use primary sequence data to identify genes that have changed function in evolutionary time have not been as successful as initially hoped. The coding sequences of most genes, which are more amenable to statistical analysis than are regulatory sequences, are generally under purifying selection, as would be expected if much evolutionary change is the result of changes in cis-regulatory sequences. Sequence-based analysis of the regulatory sequences themselves remains difficult. Comparative studies of gene expression have been useful to identify genes whose developmental role may have changed in evolutionary time and will be critical to the future development of EDG. Such studies can be used to test hypotheses of gene function. Transformation experiments are often illuminating, but can be hard to interpret, particularly if genes from multiple species are all placed into a single heterologous system such as Arabidopsis. The ideal experiment would be a gene swap or promoter swap between two species, but this awaits development of good transformation systems. The immediate need for EDG is studies of gene expression on a massive scale, far broader than any studies undertaken to date.


From real-time adaptation to social learning in robot ecosystems.
While evolutionary robotics can create novel morphologies and controllers that are well-adapted to their environments, learning is still the most efficient way to adapt to changes that occur on shorter time scales. Learning proposals for evolving robots to date have focused on new individuals either learning a controller from scratch, or building on the experience of direct ancestors and/or robots with similar configurations. Here we propose and demonstrate a novel means for social learning of gait patterns, based on sensorimotor synchronization. Using movement patterns of other robots as input can drive nonlinear decentralized controllers such as CPGs into new limit cycles, hence encouraging diversity of movement patterns. Stable autonomous controllers can then be locked in, which we demonstrate using a quasi-Hebbian feedback scheme. We propose that in an ecosystem of robots evolving in a heterogeneous environment, such a scheme may allow for the emergence of generalist task-solvers from a population of specialists.


Characterization of biofilm formation, antimicrobial resistance, and staphylococcal cassette chromosome mec analysis of methicillin resistant Staphylococcus hominis from blood cultures of children.
Methicillin resistant Staphylococcus hominis (MRSHo) has been recognized as an important human pathogen, particularly in immunocompromised patients. A total of 19 S. hominis isolates were collected from children at the Children's Medical Centre, Tehran, Iran, from March 2012 to February 2013. MRSHo susceptibility against 13 antimicrobial and 3 antiseptic agents was determined using disk diffusion (DAD) and minimum inhibitory concentration (MIC), respectively. All isolates were subjected to polymerase chain reaction (PCR) assay for 15 distinct resistance genes, staphylococcal cassette chromosome mec (SCCmec), and arginine catabolic mobile elements (ACMEs). Biofilm production of the isolates was determined using a colorimetric microtiter plate assay. Of the 19 isolates, 16 were resistant to oxacillin and harbored mecA. High resistance was also observed against trimethoprim/sulfamethoxazole (81.2%). All MRSHo isolates were susceptible to the three disinfectants tested (Septicidine-PC, Septi turbo, and Sayacept-HP). In total, 15 (78.9%) isolates produced biofilms. Three isolates had SCCmec types (V and VIII), 13 were untypable (UT), and 5 had ACME type II. The results indicate that MRSHo with high antibiotic resistance and unknown SCCmec might become a serious problem in the future for the treatment of patients such as children.


Integration of hepatitis B virus: analysis of unoccupied sites.
Hepatitis B virus (HBV) sequences integrated in the PLC/PRF/5 cell line (Alexander cells), which was derived from a human primary liver carcinoma, were previously extensively studied. Here we describe the analysis of the unoccupied sites of two linearly integrated forms of HBV DNA, AL-14 and AL-26, that were characterized previously. No major cellular DNA rearrangements were seen at the integration sites except for small deletions of host sequences: 2 kilobases of DNA in AL-14 and 17 base pairs (bp) in AL-26. The unoccupied site of AL-26 was found to be missing 182 bp, which previously mapped next to the right end of the integration sites of several independent clones. These were believed to be of cellular origin, but we show here that these 182 bp are in fact from unusual HBV sequences. Surprisingly, a region of this newly detected HBV DNA sequence is more homologous to that of woodchuck HBV DNA. Our analysis shows that the normal counterparts of both AL-14 and AL-26 contain minisatellite-like repetitive sequences. Based on the data presented here and our previous finding of HBV DNA integration at satellite sequences, we propose that genomic simple repetitive sequences are hot spots for HBV DNA integration.


Gymnothorax eurygnathos, a new moray from the Gulf of California (Anguilliformes: Muraenidae).
A new species of moray eel from deep water in the Gulf of California is described. It is dark brownish-black with an overall pattern of pale irregular blotches; a short, broad head; wide, triangular jaws; deeply serrate and partially biserial teeth; dorsal-fin origin above and behind gill opening; and 10 predorsal, 66 preanal, and 134 total vertebrae. This combination of characters is not shared by any other moray species.