Changes in temperature modulate heme oxygenase-1 induction by curcumin in renal epithelial cells.
The stress protein heme oxygenase-1 (HO-1) plays an essential role in the prevention of transplant-associated organ injury and rejection. Prior to transplantation, organs are normally subjected to variable periods of cold storage in appropriate preservation solutions. Here, we examined whether curcumin, a phenolic plant extract which strongly induces HO-1 in many cell types, could up-regulate HO-1 protein in cultured renal epithelial cells at temperatures lower than the physiological 37 degrees C. We found that stimulation of HO-1 following incubation of cells with curcumin for 6h was dramatically reduced by decreasing the temperature from 37 to 10 degrees C. Interestingly, renal cells displayed high HO-1 expression and heme oxygenase activity when exposed to a programmed change in temperature that consisted of 3h at 37 degrees C followed by 1.5h at 20 degrees C and 1.5h at 10 degrees C. Increased HO-1 levels were observed also after incubation of cells with curcumin during the programmed change in temperature under hypoxia, another feature typical of cold storage procedures. Upon challenge with an oxidant-generating system, cells pretreated with curcumin at 37 degrees C or during the programmed change in temperature exhibited increased resistance to oxidative stress-mediated injury. These findings highlight the feasibility of modulating HO-1 expression during hypothermic storage to confer tissues a better protection to counteract the damage characteristic of organ transplantation.


[Pathogenetic and morphological characteristics of acute inflammation of the central nervous system].
Virus, bacteria, mycoplasma, protozoa can be the causes of acute neuroinfections. The agents can penetrate into the brain by blood, nerve, lymphatic vessels, from the sinuses directly. Peculiarities of manifestations of acute neuroinfections depend on the agent tropism to receptors of nervous cell and specificity of brain immunoreactivity. The brain injuries can be induced by microorganism action or through immunopathologic processes. Dynamics of morphological changes in acute neuroinfections of different etiology are summarized. Histological, cytological, bacteriological, serological, immunofluorescent, histochemical methods are evaluated. Acute neuroinfection pathogenesis has many unresolved problems.


The interactions with Ro60 and La differentially affect nuclear export of hY1 RNA.
Ro RNPs are evolutionarily conserved ribonucleoprotein particles that consist of a small RNA, known as Y RNA, associated with several proteins, such as La, Ro60, and Ro52. The Y RNAs (Y1-Y5), which are transcribed by RNA polymerase III, have been shown to reside almost exclusively in the cytoplasm as Ro RNPs. To obtain more insight into the nuclear export pathway of Y RNAs, hY1 RNA export was studied in Xenopus laevis oocytes. Injection of various hY1 RNA mutants showed that an intact Ro60 binding site is a prerequisite for nuclear export, whereas the presence of an intact La binding site resulted in strong nuclear retention of hY1 RNA. Competition studies with various classes of RNAs indicated that, in addition to Ro60, another titratable factor was necessary for nuclear export of hY1 RNA. This factor appears also to be involved in nuclear export of tRNA. Because export of hY1 RNA could not be blocked by a synthetic peptide containing the recently identified nuclear export signal of the HIV-1 Rev protein, nuclear export of hY1 RNA does not seem to be dependent on a Rev-like nuclear export signal.


Stimulation of ribosomal frameshifting by antisense LNA.
Programmed ribosomal frameshifting is a translational recoding mechanism commonly used by RNA viruses to express two or more proteins from a single mRNA at a fixed ratio. An essential element in this process is the presence of an RNA secondary structure, such as a pseudoknot or a hairpin, located downstream of the slippery sequence. Here, we have tested the efficiency of RNA oligonucleotides annealing downstream of the slippery sequence to induce frameshifting in vitro. Maximal frameshifting was observed with oligonucleotides of 12-18 nt. Antisense oligonucleotides bearing locked nucleic acid (LNA) modifications also proved to be efficient frameshift-stimulators in contrast to DNA oligonucleotides. The number, sequence and location of LNA bases in an otherwise DNA oligonucleotide have to be carefully manipulated to obtain optimal levels of frameshifting. Our data favor a model in which RNA stability at the entrance of the ribosomal tunnel is the major determinant of stimulating slippage rather than a specific three-dimensional structure of the stimulating RNA element.


Ni2P promotes the hydrogenation activity of naphthalene on wrinkled silica nanoparticles with tunable hierarchical pore sizes in a large range.
Herein, a series of wrinkled silica nanoparticles with hierarchical pore (HPWSNs) supports were successfully prepared by dual-templating, and the special wrinkle pore structures in the monodisperse HPWSN samples were found to be beneficial for reducing the diffusion resistance of macromolecular aromatic compounds and achieving high dispersion of Ni2P active phases. Moreover, the distance between wrinkles in silica nanoparticles could be easily tuned by changing the ratios of SDS/CTAB through charge-reversed interactions. It was found that the Ni2P/HPWSNs-0.13 catalyst with smallest Ni2P particles had highest surface area and biggest pore volume. Furthermore, the Ni2P/HPWSNs-0.13 catalyst exhibited highest naphthalene hydrogenation conversion as well as 99.9% selectivity to decalin at 320 °C. To correlate the internal relationship between the macroscopic catalytic performance in the experiment and the atomic chemistry in the microscopic point of view, DFT calculations were performed, and the results showed that stronger adsorptions of naphthalene and tetralin occurred over the Ni(2) sites than those over the Ni(1) sites. Therefore, it can be concluded that the superior catalytic activity of the Ni2P/HPWSNs-0.13 catalyst is due to the synergistic effect of the center-radical framework structure and the small sizes of Ni2P particles, which are conducive to exposing more Ni(2) sites on the support surface, thus inducing more H for the naphthalene hydrogenation reaction.


Behavioral discrimination of click intensity in cat.
Avoidance conditioning procedures were used to train cats to discriminate intensity differences between successive clicks. The discriminative behavior was applied in a modified method of adjustment to determine a difference limen (DL) for click intensity. The obtained DLs were consistent within and between subjects, and averaged 4.4 db. This value is greater than previously reported intensity DLs for pure tones in cats.


Mechanism and regulation of the Two-component FMN-dependent monooxygenase ActVA-ActVB from Streptomyces coelicolor.
The ActVA-ActVB system from Streptomyces coelicolor is a two-component flavin-dependent monooxygenase involved in the antibiotic actinorhodin biosynthesis. ActVB is a NADH:flavin oxidoreductase that provides a reduced FMN to ActVA, the monooxygenase that catalyzes the hydroxylation of dihydrokalafungin, the precursor of actinorhodin. In this work, using stopped-flow spectrophotometry, we investigated the mechanism of hydroxylation of dihydrokalafungin catalyzed by ActVA and that of the reduced FMN transfer from ActVB to ActVA. Our results show that the hydroxylation mechanism proceeds with the participation of two different reaction intermediates in ActVA active site. First, a C(4a)-FMN-hydroperoxide species is formed after binding of reduced FMN to the monooxygenase and reaction with O(2). This intermediate hydroxylates the substrate and is transformed to a second reaction intermediate, a C(4a)-FMN-hydroxy species. In addition, we demonstrate that reduced FMN can be transferred efficiently from the reductase to the monooxygenase without involving any protein.protein complexes. The rate of transfer of reduced FMN from ActVB to ActVA was found to be controlled by the release of NAD(+) from ActVB and was strongly affected by NAD(+) concentration, with an IC(50) of 40 microm. This control of reduced FMN transfer by NAD(+) was associated with the formation of a strong charge.transfer complex between NAD(+) and reduced FMN in the active site of ActVB. These results suggest that, in Streptomyces coelicolor, the reductase component ActVB can act as a regulatory component of the monooxygenase activity by controlling the transfer of reduced FMN to the monooxygenase.


Ethnobotanical survey in the Palestinian area: a classification of the healing potential of medicinal plants.
An ethnobotanical survey was carried out in the West Bank to evaluate the relative efficacy of the plants used to treat skin diseases and prostate cancer. A total number of 102 informants, 30 years and older and either native born or had been living in the West Bank for more than 30 years, were interviewed using a previously prepared questionnaire. Of about 165 plant species mentioned by the informants, 63 (38.1%) were mentioned by three or more informants. On the basis of their primary uses, 21 of these plants were reported to relieve skin disorders, 17 for urinary system disorders, 16 for gastric disorders, nine for cancer and prostate disorders, eight for arthritis, five for respiratory problems, and five for other ailments. Indices on fidelity levels (FLs), relative popularity level (RPL), and rank-order priority (ROP) were calculated. Plants were classified in two groups: 'popular' (RPL=1) or 'unpopular' (RPL<1). The following plant species were classified as popular in this study: Teucrium polium, Matricaria aurea, Urtica pilulifera, Paronychia argentea, Petroselinum sativum, and Salvia fruticosa. The remaining 57 species were classified as 'unpopular'. Fifty-nine plants were claimed to be effective against cancer and prostate disorders, which include Arum dioscorides, U. pilulifera, Allium sativum, Viscum cruciatum, and Allium cepa.


A Cardiopulmonary Exercise Testing for Prescribing High-Intensity Interval Training Sessions with Elastic Resistance.
This study aims to analyze the agreement of cardiopulmonary variables between a cardiopulmonary exercise test with elastic resistance (CPxEL) and high-intensity interval exercise with elastic resistance (EL-HIIE). Twenty-two physically independent participants were recruited. Visit one consisted of conducting a health survey and anthropometric assessment. On visit two, the participants performed CPxEL. After seven days, on visit three, the participants performed EL-HIIE. The CPxEL was carried out on a rubber mat demarcated by lines representing eight stages. The test consisted of alternating back and forth steps against elastic resistance. The increments were performed at a rate of one stage per minute, following a cadence controlled by a metronome calibrated by beats per minute (bpm). The EL-HIIE was performed at the stage corresponding to an intensity of ~85% VO2max, as determined by CPxEL. The EL-HIIE consisted of 10 × 1 min (work):1 min (passive rest), with a cadence of 200 bpm. Cardiopulmonary parameters, heart rate (HR), and oxygen consumption (VO2) were measured during exercise. Bland-Altman was applied to analyze the agreement between the HR and VO2 found in EL-HIIE and the values prescribed by CPxEL (~85-90% VO2max). The HRpeak and VO2peak in the EL-HIIE showed good agreement with the VO2CPxEL and HRCPxEL values, showing an average difference of (-1.7 mL·kg-1·min-1) and (0.3 bpm). The results of the present study demonstrate the agreement of cardiopulmonary variables between the CPxEL and the EL-HIIE. Therefore, for a more specific prescription of EL-HIIE intensity, CPxEL can be used.


Relationship of abdominal adiposity and dyslipemic status in women with a common mutation in the lipoprotein lipase gene. The REGICOR investigators.
Abdominal obesity constitutes an important risk factor for cardiovascular disease. Hypertriglyceridemia and low high-density lipoprotein (HDL) cholesterol concentration constitute the major lipid alterations observed in obesity. A common variant of the lipoprotein lipase (LPL) gene, the HindIII polymorphism, has been found to be associated with changes in triglyceride and HDL-cholesterol levels. We have investigated the impact of the LPL HindIII polymorphism on the relationship between abdominal adiposity and lipoprotein concentrations in 156 randomly selected women in a cross-sectional study conducted in the province of Gerona, in the northeast of Spain. The waist-to-hip ratio was used as an estimate of regional fat distribution. Serum lipid and lipoprotein measurements as well as lipoprotein lipase-HindIII genotypes were determined. Percentile 50 of waist-to-hip ratio (WHR) (0.81) was used as a cutoff to define low or high WHR groups, which significantly differed in blood pressure and lipid trait concentrations. Serum triglyceride concentrations and mean log triglyceride-to-HDL-cholesterol ratio were significantly higher in H+ homozygous women compared with H- carriers. Whereas no statistically-significant differences were observed in HDL-cholesterol concentration and log triglyceride-to-HDL-cholesterol ratio of H- carriers between WHR groups, H+ homozygous women showed significant differences in these lipid traits. It is noteworthy that high-WHR H- carrier women showed a mean HDL-cholesterol value similar to those of both genotypes in the low WHR group. A statistically significant interaction between WHR and genotype was observed for HDL-cholesterol concentration (P=0. 027) and log triglyceride-to-HDL-cholesterol ratio (P=0.040). These results stress the compensating effects that weight loss may have on women with adverse genetic factors. From a complementary viewpoint, the presence of the H- allele seems to confer a protective lipid profile, even when an adverse anthropometric factor such as abdominal adiposity is present.


Semisolid systems containing propolis for the treatment of periodontal disease: in vitro release kinetics, syringeability, rheological, textural, and mucoadhesive properties.
Formulations containing poloxamer 407 (P407), carbopol 934P (C934P), and propolis extract (PE) were designed for the treatment of periodontal disease. Gelation temperature, in vitro drug release, rheology, hardness, compressibility, adhesiveness, mucoadhesion, and syringeability of formulations were determined. Propolis release from formulations was controlled by the phenomenon of relaxation of polymer chains. Formulations exhibited pseudoplastic flow and low degrees of thixotropy or rheopexy. In most samples, increasing the concentration of C934P content significantly increased storage modulus (G'), loss modulus (G''), and dynamic viscosity (eta'), at 5 degrees C, G'' exceeded G'. At 25 and 37 degrees C, eta' of each formulation depended on the oscillatory frequency. Formulations showed thermoresponsive behavior, existing as a liquid at room temperature and gel at 34-37 degrees C. Increasing the C934P content or temperature significantly increased formulation hardness, compressibility, and adhesiveness. The greatest mucoadhesion was noted in the formulation containing 15% P407 (w/w) and 0.25% C934P (w/w). The work of syringeability values of all formulations were similar and very desirable with regard to ease of administration. The data obtained in these formulations indicate a potentially useful role in the treatment of periodontitis and suggest they are worthy of clinical evaluation.


Spirometry and Bronchodilator Test.
Spirometry is a physiological test for assessing the functional aspect of the lungs using an objective indicator to measure the maximum amount of air that a patient can inhale and exhale. Acceptable spirometry testing needs to be conducted three times by an acceptable and reproducible method for determining forced vital capacity (FVC). Until the results of three tests meet the criteria of reproducibility, the test should be repeated up to eight times. Interpretation of spirometry should be clear, concise, and informative. Additionally, spirometry should guarantee optimal quality prior to the interpreting spirometry results. Our guideline adopts a fixed normal predictive value instead of the lower limit of normal as the reference value because fixed value is more convenient and also accepts FVC instead of vital capacity (VC) because measurement of VC using a spirometer is impossible. The bronchodilator test is a method for measuring the changes in lung capacity after inhaling a short-acting β-agonist that dilates the airway. When an obstructive ventilatory defect is observed, this test helps to diagnose and evaluate asthma and chronic obstructive pulmonary disease by measuring reversibility with the use of an inhaled bronchodilator. A positive response to a bronchodilator is generally defined as an increase of ≥12% and ≥200 mL as an absolute value compared with a baseline in either forced expiratory volume at 1 second or FVC.


Purification and characterization of a transcription factor that confers promoter specificity to human RNA polymerase I.
A whole-cell HeLa extract was fractionated into two components required for accurate in vitro transcription of human rRNA. One fraction contained endogenous RNA polymerase I, and the second component contained a factor (SL1) that confers promoter selectivity to RNA polymerase I. Analysis of mutant templates suggests that the core control element of the rRNA promoter is required for activation of transcription by SL1. We purified SL1 approximately 100,000-fold by column chromatography and have shown that the addition of SL1 can reprogram the otherwise nonpermissive mouse transcription system to recognize and initiate accurate RNA synthesis from human rDNA. Antibodies raised against SL1 bind preferentially to a protein localized in the nucleolus of primate cells and specifically inhibit in vitro transcription initiating from the human rRNA promoter. By contrast, anti-SL1 does not react with the nucleolus of rodent cells and has no effect on the in vitro synthesis of mouse rRNA by a transcription system derived from mouse cells. These findings suggest that SL1 is a selectivity factor present in the nucleolus that imparts promoter recognition to RNA polymerase I and that can discriminate between rRNA promoters from different species.


Imperatorin ameliorates kidney injury in diabetic mice by regulating the TGF-β/Smad2/3 signaling axis, epithelial-to-mesenchymal transition, and renal inflammation.
Diabetic nephropathy (DN) is a serious concern in patients with diabetes mellitus. Prolonged hyperglycemia induces oxidative damage, chronic inflammation, and build-up of extracellular matrix (ECM) components in the renal cells, leading to kidney structural and functional changes. Imperatorin (IMP) is a naturally occurring furanocoumarin derivative with proven antioxidative and anti-inflammatory properties. We investigated whether IMP could improve DN and employed high glucose (HG)-induced HK-2 cells and high-fat diet-fed streptozotocin (HFD/STZ)-generated DN experimental model in C57BL/6 J mice. In vitro, IMP effectively reduced the HG-activated reactive oxygen species generation, disturbance in the mitochondrial membrane potential (MMP) and epithelial-to-mesenchymal transition (EMT)-related markers, and the transforming growth factor (TGF)-β and collagen 1 expression in HK-2 cells. In vivo, we found an elevation of serum creatinine, kidney histology alterations, and collagen build-up in the kidneys of the DN control group. Also, we found that altered expression of EMT-related markers, upregulation of the TGF-β/Smad2/3 axis, and elevated pro-inflammatory molecules, TNF-α, IL-1β, IL-18 and phospho-NF-kB (p65) in the DN control group. IMP treatment did not significantly reduce the blood glucose level compared to the DN control group. However, IMP treatment effectively improved renal damage by ameliorating kidney histological changes and serum renal injury markers. IMP treatment restored renal antioxidants and exhibited anti-inflammatory effects in the kidneys. Moreover, the abnormal manifestation of EMT-related attributes and elevated levels of TGF-β, phospho-Smad2/3, and collagen 1 were also normalized in the IMP treatment group. Our findings highlight that IMP may be a potential candidate for treating DN.


Working under pressure: a pilot study of nurse work in a postoperative setting.
Postoperative services provide an excellent setting to study nursing work due to the patients' needing highly technical, yet highly comforting, care. The current study examined nursing work in postoperative services in an attempt to discern how nursing work is structured. Observations of nursing interactions in a 14-bed postoperative unit of a large Swedish university hospital found that nursing work in this setting is highly intensive and multidimensional. The need to provide nursing interactions that are caring and respectful of patients, while at the same time ensuring a high level of technical capacity, was obvious throughout all stages of patient stays in this unit. Furthermore, although each interaction is necessarily time-limited there is a caring relationship sustained with each patient. There is a pattern of caring that emerges that can be encapsulated as a "contingent routine." Nursing work cannot be broken down into "dimensions of caring." The work is high-pressure and involves, by necessity, multitasking. There are many dimensions of nursing care, but, usually, these are supplied simultaneously.


Night heart rate variability and particulate exposures among boilermaker construction workers.
Although studies have documented the association between heart rate variability (HRV) and ambient particulate exposures, the association between HRV, especially at night, and metal-rich, occupational particulate exposures remains unclear. Our goal in this study was to investigate the association between long-duration HRV, including nighttime HRV, and occupational PM(2.5) exposures. We used 24-hr ambulatory electrocardiograms (ECGs) to monitor 36 male boilermaker welders (mean age of 41 years) over a workday and nonworkday. ECGs were analyzed for HRV in the time domain; rMSSD (square root of the mean squared differences of successive intervals), SDNN (SD of normal-to-normal intervals over entire recording), and SDNN(i) (SDNN for all 5-min segments) were summarized over 24-hr, day (0730-2130 hours), and night (0000-0700 hours) periods. PM(2.5) (particulate matter with an aerodynamic diameter </= 2.5 microm) exposures were monitored over the workday, and 8-hr time-weighted average concentrations were calculated. We used linear regression to assess the associations between HRV and workday particulate exposures. Matched measurements from a nonworkday were used to control for individual cardiac risk factors. Mean (+/- SD) PM(2.5) exposure was 0.73 +/- 0.50 mg/m(3) and ranged from 0.04 to 2.70 mg/m(3). We observed a consistent inverse exposure-response relationship, with a decrease in all HRV measures with increased PM(2.5) exposure. However, the decrease was most pronounced at night, where a 1-mg/m(3) increase in PM(2.5) was associated with a change of -8.32 [95% confidence interval (CI), -16.29 to -0.35] msec nighttime rMSSD, -14.77 (95% CI, -31.52 to 1.97) msec nighttime SDNN, and -8.37 (95% CI, -17.93 to 1.20) msec nighttime SDNN(i), after adjusting for nonworking nighttime HRV, age, and smoking. Metal-rich particulate exposures were associated with decreased long-duration HRV, especially at night. Further research is needed to elucidate which particulate metal constituent is responsible for decreased HRV.


Frequency of facial angiofibromas in Japanese patients with multiple endocrine neoplasia type 1.
The high frequency of cutaneous manifestations in patients with multiple endocrine neoplasia type 1 (MEN 1) has recently been reported. Since prevalence of some cutaneous diseases varies among different ethnic groups, we examined the frequency of facial angiofibromas in Japanese patients with familial MEN 1. Among 27 patients with germline MEN1 gene mutation and one asymptomatic gene carrier, angiofibromas were identified in 43% (12/28) of the subjects. This frequency was significantly lower than that of Caucasian patients, but nonetheless almost equaled those of pituitary tumors and pancreas endocrine tumors. Angiofibromas should be considered as one of major manifestations in MEN 1 regardless of patients' ethnic origin, and clinicians should pay careful attention to the cutaneous lesions in patients with endocrine tumors.


Removal of kidney stones by extracorporeal shock wave lithotripsy is associated with delayed progression of chronic kidney disease.
This study aimed to elucidate whether stone removal by extracorporeal shock wave lithotripsy (ESWL) is associated with delayed chronic kidney disease (CKD) progression. We conducted a retrospective analysis of 131 nephrolithiasis patients with stage 3 and 4 CKD. We collected baseline clinical and laboratory data, kidney stone characteristics, and history of receiving ESWL. We classified study patients into two groups according to whether they underwent ESWL or not (Non-ESWL group vs. ESWL group). We initially compared annual estimated glomerular filtration rate (eGFR) changes of Non-ESWL group with those of ESWL group before undergoing ESWL. In the next step, we sought to compare annual eGFR changes in the same patients before and after ESWL. Finally, we compared annual eGFR changes between success and failure groups among patients undergoing ESWL. The mean age of the patients was 62 years and 72.5% were male. The mean observation period was 3.2 years. Non-ESWL group and ESWL group before undergoing ESWL showed similar annual eGFR changes (-1.75±6.5 vs. -1.63±7.2 mL/min/1.73 m²/year, p=0.425). However, eGFR declined slower after undergoing ESWL than before ESWL (annual eGFR changes, -0.29±6.1 vs. -1.63±7.2 mL/min/1.73 m²/year, p<0.05). In addition, among patients in ESWL group, eGFR declined faster in the failure group than in the success group (annual eGFR change, -1.01±4.7 vs. -0.05±5.2 mL/min/1.73 m²/year, p<0.05). Our results suggest that stone removal by ESWL is associated with delayed deterioration of renal function in CKD patients with nephrolithiasis.


Genome-Wide Association Analyses Reveal Genomic Regions Controlling Canopy Wilting in Soybean.
Drought stress causes the greatest soybean [Glycine max (L.) Merr.] yield losses among the abiotic stresses in rain-fed U.S. growing areas. Because less than 10% of U.S. soybean hectares are irrigated, combating this stress requires soybean plants which possess physiological mechanisms to tolerate drought for a period of time. Phenotyping for these mechanisms is challenging, and the genetic architecture for these traits is poorly understood. A morphological trait, slow or delayed canopy wilting, has been observed in a few exotic plant introductions (PIs), and may lead to yield improvement in drought stressed fields. In this study, we visually scored wilting during stress for a panel of 162 genetically diverse maturity group VI-VIII soybean lines genotyped with the SoySNP50K iSelect BeadChip. Field evaluation of canopy wilting was conducted under rain-fed conditions at two locations (Athens, GA and Salina, KS) in 2015 and 2016. Substantial variation in canopy wilting was observed among the genotypes. Using a genome-wide association mapping approach, 45 unique SNPs that tagged 44 loci were associated with canopy wilting in at least one environment with one region identified in a single environment and data from across all environments. Several new soybean accessions were identified with canopy wilting superior to those of check genotypes. The germplasm and genomic regions identified can be used to better understand the slow canopy wilting trait and be incorporated into elite germplasm to improve drought tolerance in soybean.


Seasonality in depressive and anxiety symptoms among primary care patients and in patients with depressive and anxiety disorders; results from the Netherlands Study of Depression and Anxiety.
Little is known about seasonality of specific depressive symptoms and anxiety symptoms in different patient populations. This study aims to assess seasonal variation of depressive and anxiety symptoms in a primary care population and across participants who were classified in diagnostic groups 1) healthy controls 2) patients with a major depressive disorder, 3) patients with any anxiety disorder and 4) patients with a major depression and any anxiety disorder. Data were used from the Netherlands Study of Depression and Anxiety (NESDA). First, in 5549 patients from the NESDA primary care recruitment population the Kessler-10 screening questionnaire was used and data were analyzed across season in a multilevel linear model. Second, in 1090 subjects classified into four groups according to psychiatric status according to the Composite International Diagnostic Interview, overall depressive symptoms and atypical versus melancholic features were assessed with the Inventory of Depressive Symptoms. Anxiety and fear were assessed with the Beck Anxiety Inventory and the Fear questionnaire. Symptom levels across season were analyzed in a linear regression model. In the primary care population the severity of depressive and anxiety symptoms did not show a seasonal pattern. In the diagnostic groups healthy controls and patients with any anxiety disorder, but not patients with a major depressive disorder, showed a small rise in depressive symptoms in winter. Atypical and melancholic symptoms were both elevated in winter. No seasonal pattern for anxiety symptoms was found. There was a small gender related seasonal effect for fear symptoms. Seasonal differences in severity or type of depressive and anxiety symptoms, as measured with a general screening instrument and symptom questionnaires, were absent or small in effect size in a primary care population and in patient populations with a major depressive disorder and anxiety disorders.


Extrusion-based technologies for 3D printing: a comparative study of the processability of thermoplastic polyurethane-based formulations.
Thermoplastic polyurethanes (TPU) offer excellent properties for a wide range of dosage forms. These polymers have been successfully utilized in personalized medicine production using fused deposition modeling (FDM) 3D printing (3DP). However, direct powder extrusion (DPE) has been introduced recently as a challenging technique since it eliminates filament production before 3DP, reducing thermal stress, production time, and costs. This study compares DPE and single-screw extrusion for binary (drug-TPU) and ternary (drug-TPU-magnesium stearate [MS]) mixtures containing from 20 to 60% w/w of theophylline. Powder flow, mechanical properties, fractal analysis, and percolation theory were utilized to analyze critical properties of the extrudates. All the mixtures could be processed at a temperature range between 130 and 160 °C. Extrudates containing up to 50% w/w of drug (up to 30% w/w of drug in the case of single-screw extrusion binary filaments) showed toughness values above the critical threshold of 80 kg/mm2. MS improved flow in mixtures where the drug is the only percolating component, reduced until 25 °C the DPE temperature and decreased the extrudate roughness in high drug content systems. The potential of DPE as an efficient one-step additive manufacturing technique in healthcare environments to produce TPU-based tailored on-demand medicines has been demonstrated.


Dnmt3b Deficiency in Myf5+-Brown Fat Precursor Cells Promotes Obesity in Female Mice.
Increasing energy expenditure through activation of brown fat thermogenesis is a promising therapeutic strategy for the treatment of obesity. Epigenetic regulation has emerged as a key player in regulating brown fat development and thermogenic program. Here, we aimed to study the role of DNA methyltransferase 3b (Dnmt3b), a DNA methyltransferase involved in de novo DNA methylation, in the regulation of brown fat function and energy homeostasis. We generated a genetic model with Dnmt3b deletion in brown fat-skeletal lineage precursor cells (3bKO mice) by crossing Dnmt3b-floxed (fl/fl) mice with Myf5-Cre mice. Female 3bKO mice are prone to diet-induced obesity, which is associated with decreased energy expenditure. Dnmt3b deficiency also impairs cold-induced thermogenic program in brown fat. Surprisingly, further RNA-seq analysis reveals a profound up-regulation of myogenic markers in brown fat of 3bKO mice, suggesting a myocyte-like remodeling in brown fat. Further motif enrichment and pyrosequencing analysis suggests myocyte enhancer factor 2C (Mef2c) as a mediator for the myogenic alteration in Dnmt3b-deficient brown fat, as indicated by decreased methylation at its promoter. Our data demonstrate that brown fat Dnmt3b is a key regulator of brown fat development, energy metabolism and obesity in female mice.


Laser-Activated Gene Silencing via Gold Nanoshell-siRNA Conjugates.
The temporal and spatial control over the delivery of materials such as siRNA into cells remains a significant technical challenge. We demonstrate the pulsed near-infrared (NIR) laser-dependent release of siRNA from coated 40 nm gold nanoshells. Tat-lipid coating mediates the cellular uptake of the nanomaterial at picomolar concentration, while spatiotemporal silencing of a reporter gene (green fluorescence protein) was studied using photomasking. The NIR laser-induced release of siRNA from the nanoshells is found to be power- and time-dependent, through surface-linker bond cleavage, while the escape of the siRNA from endosomes occurs above a critical pulse energy attributed to local heating and cavitation. NIR laser-controlled drug release from functional nanomaterials should facilitate more sophisticated developmental biology and therapeutic studies.


Trophoblastic pseudotumor: An illustrative case.
A case of trophoblastic pseudotumor of the uterus is presented. Erroneous interpretations of the specimens derived from curettage and hysterectomy resulted in surgery and chemotherapy. Emphasis in this report is on histologic criteria which aid in distinguishing this lesion from choriocarcinoma. Hormone production and persistence of the tumor for several months after curettage are also documented.


Synthetic human alpha-atrial natriuretic peptide improves the management of postoperative hypertension and renal dysfunction after the repair of abdominal aortic aneurysm.
Delayed hypertension (HT) and renal dysfunction (RD) are observed after aortic operations accompanied by infra-renal aortic cross-clamping (AXC). Atrial natriuretic peptide (ANP) has effects on vasodilation and renal protection, and we examined the hypothesis that synthetic human alpha-ANP (hANP) improves the postoperative management for abdominal aortic aneurysm (AAA). Fifty patients undergoing elective aneurysmectomy for infrarenal-AAA between 1998 and 2001 (M:F = 43:7, mean age 70.5 +/- 7.7 years) were randomly allocated to one of 2 groups; Group H (n = 24) received hANP immediately after operation (initial dose: 0.025 microg/kg/min), and Group C (n = 26) served as a control group. All patients in Group C required nicardipine hydrochloride (4.41 +/- 1.68 mg/h) for prevention of postoperative HT, whereas only 6 patients in Group H required the increase in hANP dose due to HT (P < 0.0001). Maximum hANP dose was 0.035 +/- 0.019 microg/kg/min. Group H showed significantly smaller furosemide dosage in the initial 3 days (H vs. C; 9.2 +/- 11.0 vs. 58.8 +/- 41.5 mg, P < 0.0001), significantly lower peak-Crn (H vs. C; 1.16 +/- 0.53 vs. 2.58 +/- 1.42 mg/dL, P < 0.0001), and significantly lower plasma renin-activity (7.09 +/- 2.38 vs. 11.52 +/- 4.89 ng/mL/h, P = 0.0002) and aldosterone (51.6 +/- 12.7 vs. 81.2 +/- 34.2 pg/mL, P = 0.0002) on the first postoperative day than Group C did. These results imply that renin-angiotensin system may play a role in the incidence of postoperative HT and RD, and suggest that hANP infusion is a simple, reliable, and effective method for management during the immediate period after AAA operations.


Randomized controlled trial of a new portable calf compression device (Venowave) for prevention of venous thrombosis in high-risk neurosurgical patients.
Patients undergoing neurosurgical procedures are at risk of venous thromboembolism (VTE), but often have contraindications for anticoagulant prophylaxis. To assess the efficacy and tolerability of a new, lightweight, portable, battery-powered, intermittent calf compression device, Venowave, for the prevention of VTE in neurosurgical inpatients. We performed an open randomized controlled trial comparing Venowave with control for the prevention of VTE in patients undergoing neurosurgery. The primary outcome was the composite of asymptomatic deep vein thrombosis (DVT) detected by screening venography or compression ultrasound performed on day 9 (± 2 days) and symptomatic VTE. We randomized 75 patients to receive Venowave devices and 75 to the control group. All patients were prescribed graduated compression stockings and physiotherapy. VTE occurred in three patients randomized to Venowave and in 14 patients randomized to control (4.0% vs. 18.7%, relative risk 0.21; 95% confidence interval 0.05-0.75, P = 0.008). Similar reductions were seen for proximal DVT (2.7% vs. 8.0%) and symptomatic VTE (0% vs. 2.7%), and the results were consistent in all subgroups examined. Venowave devices are effective in preventing VTE in high-risk neurosurgical patients.


Monitoring of polycyclic aromatic hydrocarbon contamination at four oil spill sites using fluorescence spectroscopy coupled with parallel factor-principal component analysis.
Fluorescence spectroscopy analysis of oil and environmental samples collected from four oil spill incidents in Canada-a 2016 pipeline spill into the North Saskatchewan River (NSR), Saskatchewan; a 2015 train derailment in Gogama, Ontario; the 1970 sinking of the SS Arrow ship in Chedabucto Bay, Nova Scotia; and the 1970 sinking of the Irving Whale barge in the Gulf of St. Lawrence-permitted assessment of the PAH content of environmentally weathered samples. A recently developed fluorescence fingerprinting model based on excitation-emission matrix-parallel factor analysis-principal component analysis (EEM-PARAFAC-PCA) was applied to (i) evaluate the intensity of the abundant PAH groups in the samples, (ii) investigate changes in the PAH composition of environmental samples over time due to weathering, and (iii) classify the original spilled oil and environmental samples within the already established classes of the fingerprinting PCA model. The environmental sediment samples collected from the Husky Energy spill site show loss of PAHs occurring over the course of 15 months post-spill. However, the extent of weathering depends on several environmental factors rather than solely the time of weathering, the PAH loss was maximum at 15 months. There was a decrease in the PAH content of the environmental samples of Gogama spill collected 20 months post-spill. Almost all of Gogama environmental sediment samples underwent substantial weathering, making PCA classification impractical. The SS Arrow and Irving Whale samples fell within adjacent PCA groups, as they both had a similar type of spilled oil (Bunker C) with similarity in chemical composition.


Natural and engineered nicking endonucleases--from cleavage mechanism to engineering of strand-specificity.
Restriction endonucleases (REases) are highly specific DNA scissors that have facilitated the development of modern molecular biology. Intensive studies of double strand (ds) cleavage activity of Type IIP REases, which recognize 4-8 bp palindromic sequences, have revealed a variety of mechanisms of molecular recognition and catalysis. Less well-studied are REases which cleave only one of the strands of dsDNA, creating a nick instead of a ds break. Naturally occurring nicking endonucleases (NEases) range from frequent cutters such as Nt.CviPII (^CCD; ^ denotes the cleavage site) to rare-cutting homing endonucleases (HEases) such as I-HmuI. In addition to these bona fida NEases, individual subunits of some heterodimeric Type IIS REases have recently been shown to be natural NEases. The discovery and characterization of more REases that recognize asymmetric sequences, particularly Types IIS and IIA REases, has revealed recognition and cleavage mechanisms drastically different from the canonical Type IIP mechanisms, and has allowed researchers to engineer highly strand-specific NEases. Monomeric LAGLIDADG HEases use two separate catalytic sites for cleavage. Exploitation of this characteristic has also resulted in useful nicking HEases. This review aims at providing an overview of the cleavage mechanisms of Types IIS and IIA REases and LAGLIDADG HEases, the engineering of their nicking variants, and the applications of NEases and nicking HEases.


Self-reported dry mouth among ageing people: a longitudinal, cross-national study.
Focusing on Swedish and Norwegian cohorts of community-dwelling older adults between age 65 and 70, this study aimed to identify predictors of the prevalence and incident cases of daytime and night-time xerostomia. It was hypothesized that the prevalence increases with increasing age and is higher in women than in men and that the prevalence of persistent xerostomia and the 5-yr-incident cases are higher in people with consistent use of medication and need for health care. Of the Norwegian participants who completed the 2007 survey (age 65 yr), 70% (n = 2,947) participated in 2012. Individuals participating in both 2007 and 2012 constituted the Swedish panel (80%, n = 4,862). The prevalence of xerostomia was higher in women than in men and increased from age 65 to age 70, most markedly in the Swedish cohort. The risk of persistent xerostomia was greatest for participants with consistent use of medication (OR = 1.3) and contact with a physician (OR = 2.3). The risk of incident cases of xerostomia during daytime was greatest for participants with recent and consistent use of medication and recent contact with a physician. Dental professionals should identify patients with xerostomia, emphasize early prevention, and alleviate oral symptoms in collaboration with physicians.


Study of factors that may predispose domestic cats to road traffic accidents: Part 2.
Between March 2000 and February 2001, six veterinary practices in Cambridgeshire collected data on 117 owned cats which they had examined after a road traffic accident (RTA). The owners of 66 of these cats completed questionnaires and the information in them was compared with the information in questionnaires from a control population of 796 cats that had never been in a road accident. The RTA cats were, on average, younger than the controls; when adjusted for age the two populations did not differ with respect to the time they spent outdoors or the time they had lived at their current address. Proportionately more of the RTA cats wore reflective collars and/or lived in areas with higher levels of traffic than the controls. The accidents were evenly distributed throughout the year, and there was a trend for more accidents to happen during the night than the day. Forty-eight per cent of the accidents whose location was known occurred just outside or very near the cat's home.


[Mechanism of the anti-aggregation action of thyroxine and insulin].
Thyroxine and insulin inhibit the aggregation capacity of platelets. To study the mechanisms of the antiaggregation action of thyroxine and insulin, platelets obtained from patients with diffuse toxic goiter and from rabbits with experimental hyperinsulinemia were incubated with acetylsalicylic acid and indomethacin. Acetylsalicylic acid or indomethacin were found to suppress the aggregation activity of thyrotoxicosis patients' platelets. Acetylsalicylic acid did not inhibit the aggregation activity of platelets of the rabbits pretreated with insulin. Based on the data obtained a hypothesis is advanced according to which thyroxine inhibits the platelet aggregation, interfering with the release of arachidonic acid from phospholipids of platelets (thrombocytopathy A), whereas insulin--by blocking the cyclooxygenase activity (thrombocytopathy B).


FIESTA: an MR arthrography celebration of shoulder joint anatomy, variants, and their mimics.
Magnetic resonance (MR) arthrography is currently the gold standard radiological investigation for shoulder joint instability. Not only does this investigation allow for identification of important disease processes, but the reduced slice thickness and increased in-plane resolution allowed by the latest imaging sequences also gives excellent demonstration of shoulder joint internal anatomy. This article describes the technique of MR arthrography of the shoulder practiced at our institution, briefly outlining features of the FIESTA (fast imaging employing steady state acquisition) MR sequence employed, including its advantages and limitations. A pictorial review of shoulder MR arthrography performed with this technique is presented, concentrating on normal shoulder joint internal anatomy and anatomical variants that may mimic pathology.


Worsening renal function in patients with acute decompensated heart failure treated with ultrafiltration: predictors and outcomes.
Ultrafiltration (UF) is used to treat patients with diuretic-resistant acute decompensated heart failure. The aim of this study was to identify predictors and the effect of worsening renal failure(WRF) on mortality in patients treated with UF. Based on changes in serum creatinine, 99 patients treated with UF were divided into WRF and control groups. Overall creatinine increased from 1.9 ± 0.7 to 1.2 ± 1.0 mg/dL (P!.001),and WRF developed in 41% of the subjects. The peak UF rate was higher in the WRF group in univariate analysis (174 ± 75 vs 144 ± 52 mL/h; P = .03). Based on multivariate analysis, aldosterone antagonist treatment (odds ratio [OR] 3.38, 95% confidence interval [CI] 1.17-13.46, P = .04), heart rate ≤65 beats/min (OR 6.03, 95% CI 1.48-48.42; P = .03), and E/E0 ≥ 15 (OR 3.78, 95% CI 1.26-17.55; P 5 .04) at hospital admission were associated with WRF. Patients with baseline glomerular filtration rate (GFR) ≤60mg/dL who developed WRF during UF had a 75% 1-year mortality rate. WRF occurred frequently during UF. Increased LV filling pressures, lower heart rate, and treatment with aldosterone antagonist at hospital admission can identify patients at increased risk for WRF. Patients with baseline GFR ≤60 mg/dL and WRF during UF have an extremely high 1-year mortality rate.


CBX8 and CD96 Are Important Prognostic Biomarkers of Colorectal Cancer.
BACKGROUND Colorectal cancer (CRC) is one of the most common malignancies worldwide, with high morbidity and mortality rates. The purpose of this study was to identify potential biomarkers in the progression of CRC. MATERIAL AND METHODS Gene and isoform expression datasets of CRC was downloaded from The Cancer Genome Atlas (TCGA). EBSeq of R was used for the normalization of gene and isoform expression, as well as the identification of differential expression genes (DEGs) and isoforms (DEIs) of CRC samples compared with normal samples. The enriched functions of DEGs and DEIs were obtained based on the Database for Annotation, Visualization and Integrated Discovery (DAVID). An independent dataset, GSE38832, was downloaded from the Gene Expression Omnibus (GEO) database for survival analysis of genes with sustained decreased/increased expression values at both gene and isoform levels with the development of CRC. RESULTS A total of 2301 genes and 4241 isoforms were found to be significantly differentially expressed in stage I-IV CRC samples. They are closely associated with muscle or cell system activity. Sixteen genes were screened out with sustained decreased/increased expression values at both gene and isoform levels with the development of CRC. Aberrant CBX8 and CD96 expressions were found to be significantly associated with CRC survival. CONCLUSIONS Through combined analysis of gene and isoform expression profiles, we identified several potential biomarkers that may play an important role in the development of CRC and could be helpful in its early diagnosis and treatment.


Psychological effect of detailed preanesthetic information.
Eighty-one patients admitted for minor surgery were followed with questionnaires and self-rating scales in the pre- and post-anesthetic period to evaluate the effect of giving either routine or detailed information. The patients were randomly allocated to two groups and received either routinely given information by the anesthetist for about 5 min or more detailed information for at least 20 min. The patients' experience of the effect of the preanesthetic visit was tranquillizing and adequate in both groups. The most significant difference with detailed information was a smaller number of side-effects like slow cerebration, nausea and a general feeling of discomfort compared to the routinely informed patients. Repetitive ratings on Spielberger's State of Anxiety Scale showed that the patients who had had previous anesthetic experience were less influenced by the degree of information given. In view of the considerable numbers of parameters investigated, there were relatively few significant differences between the groups, and it was concluded that there was no convincing benefit from expanding routine to detailed information.


Identification of a corticotropin-releasing factor-binding protein in the plasma membrane of AtT-20 mouse pituitary tumor cells and its regulation by dexamethasone.
CRF stimulates the synthesis and secretion of proopiomelanocortin-derived peptides from AtT-20 mouse pituitary tumor cells. This study has shown that there is a specific binding site for CRF located on the plasma membrane of these cells. Both [125I]iodo-Tyr0CRF and noniodinated CRF (10(-11)-10(-7) M) stimulated, in a dose-dependent manner, the secretion of equimolar amounts of beta-endorphin-like immunoactivity from AtT-20 cells. Disuccinimidyl suberate, a cross-linking agent, was used to demonstrate specific binding of [125I]iodo-Tyr0CRF to plasma membranes from these cells. After cross-linking [125I] iodo-Tyr0CRF, the membrane proteins were solubilized with sodium dodecyl sulfate and electrophoresed on a 10% polyacrylamide gel. A single radioactively labeled band, corresponding to a mol wt of 66,000, was identified by autoradiography. [125I]Iodo-Tyr0CRF binding to these membranes was inhibited by 10(-7) M unlabeled CRF or an equimolar concentration of the CRF analog sauvagine. Similar concentrations (10(-7) M) of TRH, GnRH, insulin, [Arg8]vasopressin, somatostatin, and ACTH did not inhibit [125I]iodo-Tyr0CRF binding to the plasma membranes. Incubation of AtT-20 cells for 24 h in the presence of 10 nM dexamethasone reduced [125I]iodo-Tyr0CRF binding by 80% compared to that in untreated cells. Dexamethasone also inhibited the CRF-stimulated beta-endorphin-like immunoactivity secretory response. These data indicate that binding of CRF to a specific membrane protein is an integral component in the stimulation of AtT-20 cells by CRF.


[Antimycotic antibiotics (author's transl)].
A number of antibiotics having an antimycotic action are reviewed. The physicochemical and pharmacotoxicological properties, antifungal range, mechanisms of action, dosage and preparations of griseofulvin, amphotericin-B, natamycin, nystatin and pecilocin are discussed.


Factors impacting the use of antenatal care and hospital child delivery services: a case study of rural residents in the Enshi Autonomous Prefecture, Hubei Province, China.
This study was undertaken to understand the factors that impact whether rural women obtain antenatal care (ANC) and choose to use hospital delivery services in central and western China. We chose to conduct field research with the rural residents in Hubei Province through a combination of random sampling and purposive sampling methods. A mixed method approach was taken to analyze the factors impacting the use of ANC and hospital delivery services from the perspective of the villagers. Our results indicate that the quality of the available ANC services is poor. In particular, women who have special circumstances and unplanned pregnancies or who become pregnant prior to marriage are confronted with inadequate ANC and hospital child delivery services. The factors that impact whether women use or not use ANC and hospital delivery services and that cause women to choose hospital or home delivery can be understood at three levels: macro, middle, and micro. We strongly suggest that the policies and projects that promote maternal healthcare in rural areas be sustained with an added focus on including women with special circumstances. Village doctors can be enlisted to regularly visit pregnant women at home and to provide extra explanation about the ANC services available and the purpose of maternal healthcare. These findings and suggestions can be used by local health providers and decision-makers to improve the quality of ANC and hospital delivery services.


Imaging Probes and Modalities for the Study of Solute Carrier O (SLCO)-Transport Function In Vivo.
Transporters of the solute carrier O (SLCO) family, former organic anion-transporting polypeptides, are now recognized as key players in pharmacokinetics. Imaging is increasingly regarded as a relevant method to elucidate and decipher the intrinsic role of SLCO in controlling drug disposition in plasma and tissues. Current research in this representative field of translational research is based on different imaging modalities including nuclear imaging, such as single-photon emission computed tomography or positron emission tomography, and magnetic resonance imaging. Imaging modalities can be compared in terms of sensitivity, quantitative properties, spatial resolution, variety of ligands, and radiation exposure. All these approaches rely on the use of SLCO substrates that are detected using corresponding modalities. The present review aims at reporting and comparing the imaging probes that have been proposed to study SLCO-transport function, in terms of in vitro specificity, in vivo behavior, and clinical validation.


Investigating the relationship between self-perception of fracture risk and prior fracture: findings from the Hertfordshire Cohort Study.
Self-perceived risk of fracture (SPR) is associated with fracture independent of FRAX calculated risk. To understand this better we considered whether lifestyle factors not included in the FRAX algorithm and psychosocial factors (social isolation, self-efficacy, or mental health status) explain the relationship between SPR and fracture. We studied 146 UK community-dwelling older adults from the Hertfordshire Cohort Study. SPR ranked as 'lower', 'similar' and 'higher' relative to others of the same age, was assessed by questionnaire. Social isolation was assessed using the six-item Lubben Social Network Scale; self-efficacy was assessed using a shortened General Self-Efficacy Scale (GSE); mental health status was assessed using the anxiety/depression item from the EuroQoL questionnaire. SPR in relation to previous self-reported fracture was examined using logistic regression. Among participants of median age 83.4 (IQR 81.5-85.5) years, SPR was lower for 54.1% of participants, similar for 30.8%, and higher for 15.1%; 74.7% reported no previous fractures. Greater SPR was associated with increased odds of previous fractures when adjusting for sex and age only (OR 1.72, 95% CI 1.03-2.87, per higher band of SPR). While further individual adjustment for social isolation (1.73, 1.04-2.89), self-efficacy (1.71, 1.02-2.85), or mental health (1.77, 1.06-2.97) did not attenuate the relationship, individual adjustment for diet quality and number of comorbidities did. Adjustment for social isolation, self-efficacy or mental health status did not attenuate the relationship between SPR and fracture. By contrast, lifestyle factors not included in FRAX, such as diet quality, did attenuate relationships, suggesting a possible future area of investigation.


Fertility in men after treatment for stage 1 and 2A seminoma.
The purpose of this article is to assess the long-term fertility and attitudes towards fecundity in men after radical inguinal orchiectomy and radiation therapy (RT) for seminoma, and also to assess how often sperm cryopreservation is being offered to patients with seminoma prior to treatment. A retrospective review was conducted at 3 institutions (Wilford Hall Air Force Medical Center, Brooke Army Medical Center, and Fitzsimmons Army Medical Center) to identify patients who had undergone treatment of stage 1 or 2A seminoma during the period from 1975 to 1997. Seventy-three of 212 (34%) patients meeting the selection criteria of stage 1 or 2A seminoma provided information for this analysis. This was thought to be a good response rate, given that many of the patients had changed duty stations or had separated from the military by the time this study started. We performed a review of RT and tumor board records of 73 patients who were treated for testicular seminoma at selected treatment facilities from 1975 to 1997. Patients completed questionnaires and phone interviews that focused on prior fertility, the desire to father (more) children, other fertility-affecting factors (varicocele, cryptorchidism, infection, and erectile dysfunction), and incidence of physician counseling with regard to cryopreservation. All patients were asked to obtain a current semen analysis (SA). Eleven (15%) patients reported that they had tried to father children since completion of their RT. Seven of 11 (64%) successfully achieved pregnancy within a mean time of 3.5 years since RT (range: 1 month to 5 years). Of the 4 couples that were not successful, 1 had severe female factor infertility problems and a second had organic erectile dysfunction. A third had a past surgical history remarkable for vasectomy with subsequent vasectomy reversal. Nine patients provided SA. Mean sperm count and motility were 24.2 Mil/mL (range: 5-81 Mil/mL) and 63.1% (range: 30-90%), respectively (normal SA values: count = 20-250 Mil/mL, motility >50%, and volume = 1.5-5.0 mL). No patients were azoospermic. Overall mean time interval from radiation therapy was 7.9 years. Radiation dose and time since RT did not correlate with either SA results or conception. Only 16 of 73 (22%) men had been offered pretreatment sperm cryopreservation by their counseling physician. It is concluded that (1) patients who are treated for early stage seminoma by orchiectomy and RT have greater than a 50% chance of regaining normal semen parameters, and all regain at least some spermatogenesis; 2) recovery of spermatogenesis is not related to therapeutic radiation dose with the use of modern shielding and RT portals; (3) the majority of treated patients who desire children can conceive; and (4) sperm cryopreservation remains an underutilized option for seminoma patients.


Ten-year study comparing enzyme-linked immunosorbent assay with the immunofluorescent antibody test for detection of feline leukemia virus infection in cats.
Immunodetection tests for feline retroviruses are powerful tools used in modern veterinary practice. Veterinarians must fully understand the characteristics--strengths and weaknesses--of the FeLV tests so that the information gained from them can be used properly. Any FeLV ELISA or immunofluorescent antibody (IFA) test is a method for detection of FeLV infection (the virus) and is not a diagnostic test for leukemia or other feline disease. From previous studies, it was determined that the most accurate test for detection of persistent FeLV infection is the IFA test, which detects FeLV antigens in cytoplasm of leukocytes in the blood of infected cats. In the study reported here, 1,142,600 FeLV IFA tests were performed between June 1972 and December 1990. During this period 19.8% of the IFA test results were positive and 78% were negative. Evaluation was not possible for the remaining 2.2% of the tests because of lack of enough leukocytes in the smears to evaluate, or nonspecific staining reactions. In 1979, 7 years after introduction of the IFA test, in-hospital FeLV ELISA were introduced, which enabled veterinarians to test for FeLV in their hospitals. Ever since that time, continual discrepancies have been reported between results of FeLV ELISA and IFA tests, particularly between positive ELISA results and their IFA test confirmation. A 10-year comparison was made between practitioner-performed in-hospital FeLV ELISA (n = 20, 240 tests) results and FeLV IFA test performed by a commercial laboratory. All samples tested by ELISA were submitted (for confirmation of results) by veterinarians from the United States, Canada, Europe, Japan, and Australia.(ABSTRACT TRUNCATED AT 250 WORDS)


Magnesium, essential for base excision repair enzymes, inhibits substrate binding of N-methylpurine-DNA glycosylase.
N-Methylpurine-DNA glycosylase (MPG) initiates base excision repair in DNA by removing a wide variety of alkylated, deaminated, and lipid peroxidation-induced purine adducts. MPG activity and other DNA glycosylases do not have an absolute requirement for a cofactor. In contrast, all downstream activities of major base excision repair proteins, such as apurinic/apyrimidinic endonuclease, DNA polymerase beta, and ligases, require Mg(2+). Here we have demonstrated that Mg(2+) can be significantly inhibitory toward MPG activity depending on its concentration but independent of substrate type. The pre-steady-state kinetics suggests that Mg(2+) at high but physiologic concentrations decreases the amount of active enzyme concentrations. Steady-state inhibition kinetics showed that Mg(2+) affected K(m), but not V(max), and the inhibition could be reversed by EDTA but not by DNA. At low concentration, Mg(2+) stimulated the enzyme activity only with hypoxanthine but not ethenoadenine. Real-time binding experiments using surface plasmon resonance spectroscopy showed that the pronounced inhibition of activity was due to inhibition in substrate binding. Nonetheless, the glycosidic bond cleavage step was not affected. These results altogether suggest that Mg(2+) inhibits MPG activity by abrogating substrate binding. Because Mg(2+) is an absolute requirement for the downstream activities of the major base excision repair enzymes, it may act as a regulator for the base excision repair pathway for efficient and balanced repair of damaged bases, which are often less toxic and/or mutagenic than their subsequent repair product intermediates.


A case of cholangiolocellular carcinoma asynchronously developing 3 years after the resection of hepatocellular carcinoma.
Cholangiolocellular carcinoma (CLC) is a rare malignant primary liver tumor, categorized as a subtype of cholangiocellular carcinoma. CLC is considered to originate from hepatic progenitor cells, and sometimes accompanies a component of cholangiocellular carcinoma and/or hepatocellular carcinoma (HCC). We report herein a case of a 53-year-old Japanese male with CLC occurring asynchronously after a resection of HCC. At the age of 50, the patient underwent a first hepatectomy due to HCC, followed by intrahepatic recurrence. At 53, a new type of hepatic tumor was detected. Dynamic computed tomography revealed a multinodular enhanced tumor in the hepatic arterial phase, and an iso-density tumor in the portal venous and delayed phases. Living donor liver transplantation was performed for the treatment of this liver tumor because of his poor liver function. Histological findings confirmed the diagnosis of CLC. Nineteen months after the liver transplantation, bone metastasis of CLC was detected. Although the preoperative diagnosis of CLC is difficult in general, CLC should be considered as a differential diagnosis when a tumor with atypical image findings for HCC is observed after the resection of HCC. Once the diagnosis of CLC is made, postoperative surveillance of the patient must be performed, including the bone.


The International Conference on Intelligent Biology and Medicine (ICIBM) 2018: systems biology on diverse data types.
Between June 10-12, 2018, the International Conference on Intelligent Biology and Medicine (ICIBM 2018) was held in Los Angeles, California, USA. The conference included 11 scientific sessions, four tutorials, one poster session, four keynote talks and four eminent scholar talks that covered a wide range of topics in 3D genome structure analysis and visualization, next generation sequencing analysis, computational drug discovery, medical informatics, cancer genomics and systems biology. Systems biology has been a main theme in ICIBM 2018, with exciting advances presented in many areas of systems biology, covering various different data types such as gene regulation, circular RNAs expression, single-cell RNA-Seq, inter-chromosomal interactions, metabolomics, proteomics and phosphoproteomics. Here, we describe ten high quality papers to be published in BMC Systems Biology.


Inhibition of LncRNA SNHG14 protects chondrocyte from injury in osteoarthritis via sponging miR-137.
Long-chain noncoding small nucleolar RNA host gene 14 (LncRNA SNHG14) is highly expressed in various diseases and promotes diseases progression, but the role and mechanism of LncRNA SNHG14 on targeting miR-137 in promoting osteoarthritis (OA) chondrocyte injury remains unclear. To measure the expression of the LncRNAs SNHG14 and miR-137, cell survival, inflammatory response, chondrocyte apoptosis, and extracellular matrix (ECM) levels, we subjected human chondrocytes to a variety of lipopolysaccharide (LPS) concentrations. To measure the luciferase activity of SNHG14-WT and SNHG14-MUT transfected with miR-137 mimic or miR-NC mimic, luciferase reporter genes were utilized. The results showed that chondrocyte viability was significantly inhibited with LPS treatment and chondrocyte inflammatory response, apoptosis and extracellular matrix degradation were significantly increased. However, the above results were significantly reversed after LncRNA SNHG14 inhibition. The luciferase activity bound to miR-137 was decreased in SNHG14-WT group, but there was no change in SNHG14-mut group, which indicated that LncRNA SNHG14 inhibited miR-137 expression as a miRNA sponge. In conclusion, inhibition of LncRNA SNHG14 attenuates chondrocyte inflammatory response, apoptosis and extracellular matrix degradation by targeting miR-137 in LPS induced chondrocytes.


Therapeutic efficacy of Citrus aurantifolia (lime) juice in experimental Eimeria tenella-infected broiler chickens.
The purpose of the present experiment was to explore the therapeutic effect of the crude fruit juice of Citrus aurantifolia (CAJ) on Eimeria tenella disorder in chickens. One hundred twenty 3-week-old Ross 308 broilers of equal sexes were assigned to six experimental groups of 20 birds each. Groups A, B, C, D, and E were experimentally infected with 20,000 sporulated Eimeria tenella oocysts. Broilers in groups A, B, and C were infected and allocated to three treatment-graded doses of C. aurantifolia fruit juice (20, 10, and 5 mL/kg body weight, respectively) which were administered orally for 7 consecutive days of the trial. Group D was infected and treated with a reference drug, Amprolium 1.5 g/L of drinking water (positive control), group E served as infected-untreated control, and group F was uninfected and non-treated (negative control). Oocysts per gram of feces were counted using the McMaster counting device, weight gain was calculated, and blood samples from each experimental group were collected on days 0, 7, 14, 21, and 28 post-infection for hematological evaluation. Results revealed that medication of broilers with C. aurantifolia fruit juice dose-dependently increased body weight, improved cecal lesion, decreased the E. tenella oocyst production rate, and significantly (P<0.05) increased the PCV of the infected broilers. C. aurantifolia provided valuable therapeutic effects against E. tenella-induced coccidiosis in broiler chickens. The plant fruit juice should be further validated to explore the vital compounds responsible for the anticoccidial efficacy.


Activation of Lymphocyte Cytolytic Machinery: Where are We?
Target cell recognition by cytotoxic lymphocytes implies the simultaneous engagement and clustering of adhesion and activating receptors followed by the activation of an array of signal transduction pathways. The cytotoxic immune synapse represents the highly specialized dynamic interface formed between the cytolytic effector and its target that allows temporal and spatial integration of signals responsible for a defined sequence of processes culminating with the polarized secretion of lytic granules. Over the last decades, much attention has been given to the molecular signals coupling receptor ligation to the activation of cytolytic machinery. Moreover, in the last 10 years the discovery of genetic defects affecting cytotoxic responses greatly boosted our knowledge on the molecular effectors involved in the regulation of discrete phases of cytotoxic process at post-receptor levels. More recently, the use of super resolution and total internal reflection fluorescence imaging technologies added new insights on the dynamic reorganization of receptor and signaling molecules at lytic synapse as well as on the relationship between granule dynamics and cytoskeleton remodeling. To date we have a solid knowledge of the molecular mechanisms governing granule movement and secretion, being not yet fully unraveled the machinery that couples early receptor signaling to the late stage of synapse remodeling and granule dynamics. Here we highlight recent advances in our understanding of the molecular mechanisms acting in the activation of cytolytic machinery, also discussing similarities and differences between Natural killer cells and cytotoxic CD8(+) T cells.


Histopathologic features and expression of Bcl-2 and p53 proteins in primary gastric lymphomas.
The aim of this study is to present a histopathologic and immunohistochemical analysis of primary gastric lymphomas which were reclassified according to the concept of mucosa associated lymphoid tissue (MALT). The resected specimens from 41 patients with primary gastric lymphoma were investigated retrospectively. Immunohistochemical study was done to analyze the immunophenotype and bcl-2 and p53 proteins expression. Twenty three of the cases had tumors mainly located in the antrum. Histologically, 12 were low grade and 20 were high grade B-cell lymphoma of MALT, 9 other B-cell nonHodgkin's lymphomas. Helicobacter pylori was identified in 72% of the cases. According to Musshoff's modification, most of the MALT lymphoma cases had stage I or II disease. There was significant difference between low and high grade cases, in respect to depth of invasion in gastric wall. Immunohistochemically, the neoplastic cells in all MALT lymphomas expressed B-cell phenotype. Bcl-2 protein was found to be expressed in 59% and p53 protein expression was detected in 72% of cases. Among the B-cell lymphoma of MALT, bcl-2 positivity decreased and p53 positivity increased significantly as the histological grade advanced. So, an inverse correlation was observed between the expression of bcl-2 and p53. In conclusion, most primary gastric lymphomas are low or high grade B-cell MALT lymphomas and appear to arise in MALT acquired as a reaction to Helicobacter pylori infection. Expression of bcl-2 and p53 in gastric lymphomas may be associated with transformation from low-grade to high-grade disease.


Eelgrass (Zostera marina L.) in the Gulf of California:.
Discovery of Its Nutritional Value by the Seri Indians Zostera marina occurs in the northern Gulf of California. The grain of eelgrass is harvested in the spring and formed an important part of traditional Seri diet and culture. This is the only known case of a grain from the sea being used as a human food source. Eelgrass has considerable potential as a general food resource for mankind. Its cultivation would not require fresh water, pesticides, or artificial fertilizer.


[Immunomorphological characteristics of vesicular stomatitis].
The aim of the present study was to evaluate the immunomorphological characteristics of vesicular stomatitis. The patients were divided into 3 groups: 15 patients with mild stomatitis, 14 patients with moderate stomatitis, 11 patients with severe stomatitis. The cytological smears were stained by Papanicolaou method. We have evaluated indexes of maturation (MI), keratinisation (KI), destruction (DI) and inflammation-destruction (IDI). The immunocytochemistry was used to evaluate the local immune responses. Anti-CD20 (pan-B marker), Anti-CD3 (pan-T marker), CD4 (marker of T helper), CD8 (marker of T cytotoxic lymphocytes) monoclonal antibodies were used (LSAB, DAB). The comparative analysis of cytological indexes in acute and remission phases of chronic recurrent ulcerative stomatitis showed that DI and IDI decreased in remission phase compared with acute phase, but did not return to norm. It seems that inflammation persists in remission phase despite the absence of symptomatic vesicular lesion. Therefore, the evaluation of clinical efficacy of treatment requires assessing cytological indexes. In various types of vesicular stomatitis the dynamic quantitative changes of immunocompetent cells in acute and remission phases show the increased number of CD8+ T lymphocytes indicating a potential viral etiology and a persistent immunopathological reaction mediated by T cells. The presented data can be taken into account during the treatment planning and evaluation of therapeutic efficacy.


High-sugar, high-fat, and high-protein diets promote antibiotic resistance gene spreading in the mouse intestinal microbiota.
Diet can not only provide nutrition for intestinal microbiota, it can also remodel them. However, is unclear whether and how diet affects the spread of antibiotic resistance genes (ARGs) in the intestinal microbiota. Therefore, we employed selected high-sugar, high-fat, high-protein, and normal diets to explore the effect. The results showed that high-sugar, high-fat, and high-protein diets promoted the amplification and transfer of exogenous ARGs among intestinal microbiota, and up-regulated the expression of trfAp and trbBp while significantly altered the intestinal microbiota and its metabolites. Inflammation-related products were strongly correlated with the spread of ARGs, suggesting the intestinal microenvironment after diet remodeling might be conducive to the spreading of ARGs. This may be attributed to changes in bacterial membrane permeability, the SOS response, and bacterial composition and diversity caused by diet-induced inflammation. In addition, acceptor bacteria (zygotes) screened by flow cytometry were mostly Proteobacteria, Firmicutes and Actinobacteria, and most were derived from dominant intestinal bacteria remodeled by diet, indicating that the transfer of ARGs was closely linked to diet, and had some selectivity. Metagenomic results showed that the gut resistance genome could be affected not only by diet, but by exogenous antibiotic resistant bacteria (ARB). Many ARG markers coincided with bacterial markers in diet groups. Therefore, dominant bacteria in different diets are important hosts of ARGs in specific dietary environments, but the many pathogenic bacteria present may cause serious harm to human health.


Cellular immune responses against CT7 (MAGE-C1) and humoral responses against other cancer-testis antigens in multiple myeloma patients.
The type I melanoma antigen gene (MAGE) proteins CT7 (MAGE-C1) and MAGE-A3 are commonly expressed in multiple myeloma (MM), and their expression correlates with increased plasma cell proliferation and poor clinical outcome. They belong to the cancer-testis antigen (CTAg) group of tumor-associated proteins, some of which elicit spontaneous immune responses in cancer patients. CT7 and MAGE-A3 are promising antigenic targets for therapeutic tumor vaccines in myeloma; therefore, it is critical to determine if they are immunogenic in MM patients. We analyzed cellular and humoral immune responses against CTAgs in patients with plasma cell dyscrasias: MM, monoclonal gammopathy of undetermined significance (MGUS), and Waldenström's macroglobulinemia (WM). Bone marrow lymphocytes from two of four untreated MM patients exhibited CT7-specific cellular immune responses as measured by an autologous cellular immunity assay, the first such immune response to CT7 to be reported in cancer patients. Sera from 24 patients were screened by ELISA for humoral immune responses to CTAgs. Two patients with MM demonstrated positive titers, one for MAGE-A1 and the other for SSX1. These data demonstrate that CTAgs, particularly CT7, are immunogenic in MM patients and merit further exploration as targets of immunological therapy in MM.


Capsular glucan and intracellular glycogen of Mycobacterium tuberculosis: biosynthesis and impact on the persistence in mice.
Mycobacterium tuberculosis and other pathogenic mycobacterial species produce large amounts of a glycogen-like alpha-glucan that represents the major polysaccharide of their outermost capsular layer. To determine the role of the surface-exposed glucan in the physiology and virulence of these bacteria, orthologues of the glg genes involved in the biosynthesis of glycogen in Escherichia coli were identified in M. tuberculosis H37Rv and inactivated by allelic replacement. Biochemical analyses of the mutants and complemented strains indicated that the synthesis of glucan and glycogen involves the alpha-1,4-glucosyltransferases Rv3032 and GlgA (Rv1212c), the ADP-glucose pyrophosphorylase GlgC (Rv1213) and the branching enzyme GlgB (Rv1326c). Disruption of glgC reduced by half the glucan and glycogen contents of M. tuberculosis, whereas the inactivation of glgA and Rv3032 affected the production of capsular glucan and glycogen, respectively. Attempts to disrupt Rv3032 in the glgA mutant were unsuccessful, suggesting that a functional copy of at least one of the two alpha-1,4-glucosyltransferases is required for growth. Importantly, the glgA mutant was impaired in its ability to persist in mice, suggesting a role for the capsular glucan in the persistence phase of infection. Unexpectedly, GlgB was found to be an essential enzyme.


Generalization of visuomotor adaptation to different muscles is less efficient: experiment and model.
Reaching to visual targets engages the nervous system in a series of transformations between sensory information and motor commands to muscles. We recently showed that visuomotor adaptation requiring modulation of the activity of the same muscles is more efficient than adaptation requiring a transition to different muscles. Here I specifically tested for adaptation at the level of the final transformation into muscle activation by assessing generalization to unpracticed areas of the workspace, and propose a computational model with modulation of muscle synergies. In the experiment, a visuomotor rotation was applied during a center-out isometric torque production task carefully configured such that adaptation and generalization could be achieved either by only rescaling the contribution of the same muscles, or by additionally requiring the recruitment of different muscles. Consistent with our previous finding, the time course of directional errors revealed that the degree of adaptation was substantially lower (by 28.1%) for the latter case. More importantly, directional error obtained for generalization that required, in principle, to recruit different muscles from these implicated in the adaptation was more than twice that of other generalization areas. Taken together, these results suggest that modulation within an original muscle synergy contributed to visuomotor adaptation, and that synergy recomposition imposed a limitation on both adaptation and generalization. I reproduced these results with a model of the sensorimotor transformation which includes two population codes, one for the sensory network and one for the motor network. Muscle synergies are defined as linear combination of muscles by connections of the motor network, and modulation of these synergies are elicited by adaptation of the weight of these connections. Finally, I speculate that the limitation imposed on synergy recomposition originates in the balance of inhibitory and excitatory mechanisms that operate at different levels of the nervous system, and that contribute to the functional organization of muscle recruitment by focusing activity on relevant muscles.


Effects of reward sensitivity and regional brain volumes on substance use initiation in adolescence.
This longitudinal study examines associations between baseline individual differences and developmental changes in reward [i.e. behavioral approach system (BAS)] sensitivity and relevant brain structures' volumes to prospective substance use initiation during adolescence. A community sample of adolescents ages 15-18 with no prior substance use was assessed for substance use initiation (i.e. initiation of regular alcohol use and/or any use of other substances) during a 2-year follow-up period and for alcohol use frequency in the last year of the follow-up. Longitudinal 'increases' in BAS sensitivity were associated with substance use initiation and increased alcohol use frequency during the follow-up. Moreover, adolescents with smaller left nucleus accumbens at baseline were more likely to initiate substance use during the follow-up period. This study provides support for the link between developmental increases in reward sensitivity and substance use initiation in adolescence. The study also emphasizes the potential importance of individual differences in volumes of subcortical regions and their structural development for substance use initiation during adolescence.


Global Burden of Severe Tooth Loss: A Systematic Review and Meta-analysis.
The goal of the Global Burden of Disease 2010 Study has been to systematically produce comparable estimates of the burden of 291 diseases and injuries and their associated 1,160 sequelae from 1990 to 2010. We aimed to report here internally consistent prevalence and incidence estimates of severe tooth loss for all countries, 20 age groups, and both sexes for 1990 and 2010. The systematic search of the literature yielded 5,618 unique citations. After titles and abstracts were screened, 5,285 citations were excluded as clearly not relevant to this systematic review, leaving 333 for full-text review; 265 publications were further excluded following the validity assessment. A total of 68 studies-including 285,746 individuals aged 12 yr or older in 26 countries-were included in the meta-analysis using modeling resources of the Global Burden of Disease 2010 Study. Between 1990 and 2010, the global age-standardized prevalence of edentate people decreased from 4.4% (95% uncertainty interval: 4.1%, 4.8%) to 2.4% (95% UI: 2.2%, 2.7%), and incidence rate decreased from 374 cases per 100,000 person-years (95% UI: 347, 406) to 205 cases (95% UI: 187, 226). No differences were found by sex in 2010. Prevalence increased gradually with age, showing a steep increase around the seventh decade of life that was associated with a peak in incidence at 65 years. Geographic differences in prevalence, incidence, and rate of improvement from 1990 to 2010 were stark. Our review of available quality literature on the epidemiology of tooth loss shows a significant decline in the prevalence and incidence of severe tooth loss between 1990 and 2010 at the global, regional, and country levels.


A drug target for erectile dysfunction to help improve fertility, sexual activity, and wellbeing: mendelian randomisation study.
To investigate the association of genetically proxied (using a surrogate biomarker) inhibition of phosphodiesterase 5 (PDE5), an established drug target for erectile dysfunction, with fertility, sexual behaviour, and subjective wellbeing. Two sample cis-mendelian randomisation study. Summary data on genetic associations obtained from the International Consortium for Blood Pressure and UK Biobank. Individuals of European ancestry from the International Consortium for Blood Pressure (n=757 601) for estimating PDE5 inhibition (using the surrogate biomarker of diastolic blood pressure reduction), and UK Biobank (n=211 840) for estimating the fertility, sexual behaviour, and subjective wellbeing outcomes in male participants. Genetically proxied PDE5 inhibition. Number of children fathered, number of sexual partners, probability of never having had sexual intercourse, and subjective wellbeing. Genetically proxied PDE5 inhibition was associated with male participants having 0.28 (95% confidence interval 0.16 to 0.39) more children (false discovery rate corrected P<0.001). This association was not identified in female participants. No evidence was found of an association between genetically proxied PDE5 inhibition and number of sexual partners, probability of never having had sexual intercourse, or self-reported wellbeing in male participants. The findings of this study provide genetic support for PDE5 inhibition potentially increasing the number of children fathered by male individuals. Absence of this association in female participants supports increased propensity for sustained and robust penile erections as a potential underlying mechanism. Further studies are required to confirm this, however, and these findings should not promote indiscriminate use of PDE5 inhibitors, which can also have harmful adverse effects.


NanoProbeArrays for the analysis of ultra-low-volume protein samples using piezoelectric liquid dispensing technology.
Antibody microarrays are gaining popularity as a high-throughput technology to investigate the proteome. However, protein extracts from most body fluid or biopsy samples are available in very small volumes and are often unsuitable for large-scale antibody microarray studies. To demonstrate the potential for protein analysis with as little as a few nanoliters of sample, we have developed a new technology called NanoProbeArrays based on piezoelectric liquid dispensing for non-contact printing and probing of antibody arrays. Instead of flooding the protein sample on the antibody microarray surface, as in conventional microarray screening, a piezoelectric inkjet printer is used to dispense nanoliters of fluorescently labeled proteins over the antibody spots on the array. The ability of NanoProbeArrays to precisely identify and reliably distinguish between test proteins from different sources, without any loss of sensitivity and specificity as compared with conventional antibody microarrays, is illustrated here. The utility of NanoProbeArrays for biomarker identification in a complex biological sample was tested by detecting the cytokine interleukin-4 in serum. The significant reduction in volume of sample during NanoProbeArray analysis, as compared with conventional antibody microarrays, offers new opportunities for basic and applied proteomic research.


Discrepancy of C-Reactive Protein, Procalcitonin and Interleukin-6 at Hospitalization: Infection in Patients with Normal C-Reactive Protein, Procalcitonin and High Interleukin-6 Values.
C-reactive protein (CRP) or procalcitonin (PCT) alone has limitations in the early detection of infection or inflammation due to shortcomings in specificity and varied cut-off values. Recently, interleukin (IL)-6 has been assessed, but it is not known to what extent the three values are homogeneous in reality. This retrospective study was conducted with two large datasets (discrepancy set with results within 24 h of admission [7149 patients] and follow-up set until 2 weeks of hospital stay [5261 tests]) consisting of simultaneous examinations of CRP, PCT, and IL-6 between January 2015 and August 2021. The specific discrepant group (n = 102, 1.4%) with normal CRP (<10 mg/L) and PCT (<0.1 ng/mL) and high IL-6 (≥100 pg/mL) values was extracted from the discrepancy set. Dimensionality reduction and visualization were performed using Python. The three markers were not clearly clustered after t-distributed stochastic neighbor embedding. Pearson's correlation coefficients between two markers were substantially low (0.23−0.55). Among the high normalized IL-6 levels (≥0.5) (n = 349), 17.8% and 38.7% of CRP and PCT levels were very low (≤0.01). 9.2% and 13.4% of normal CRP (n = 1522) had high PCT (≥0.5 ng/mL) and IL-6 (≥100 pg/mL) values, respectively. Infection and bacteremia among 102 patients occurred in 36 (35.3%) and 9 (8.8%) patients, respectively. In patients with bacteremia, IL-6 was the first to increase, followed by PCT and CRP. Our study revealed that CRP, PCT, and IL-6 levels were considerably discrepant, which could be misinterpreted if only CRP tests are performed.


Excessive gestational weight gain in the first trimester among women with normal glucose tolerance and resulting neonatal adiposity.
To assess whether weight gain above or below Institute of Medicine (IOM) recommended amounts in an ethnically diverse obstetric population with normal glucose tolerance is associated with differences in neonatal adiposity. In this prospective cohort study, healthy women with normal glucose tolerance based on the International Association of Diabetes and Pregnancy Study Groups guidelines were enrolled. Gestational weight at multiple time points were collected. Neonatal adiposity was measured by air displacement plethysmography at 24 to 72 h of life. Analyses included Fisher's exact test, analysis of variance and a trajectory analysis using a group-based weight gain trajectory model with a censored normal distribution. Overweight and obese women were more likely to exceed IOM weight gain guidelines. Regardless, there was no significant difference in %body fat of neonates born to mothers who either met or exceeded gestational weight gain (GWG) guidelines. GWG timing influenced neonatal anthropometrics: women who gained excessively by the first prenatal visit had neonates with significantly higher birth weight (3.91 vs 3.45 kg, P<0.001) and %body fat (13.7 vs 10.9%, P=0.0001) compared with women who had steady and moderate GWG. Avoidance of excessive GWG in the first trimester may prevent high amounts of neonatal adiposity.


Expanding the chemical structure space of opto-electronic molecular materials: unprecedented push-pull chromophores by reaction of a donor-substituted tetracyanofulvene with electron-rich alkynes.
The reaction of a 3,5-bis(N,N-dimethylanilino)-substituted 2,4,6,6-tetracyanopentafulvene (TCPF) with mono- and bis(N,N-dimethylanilino)acetylene provides facile access to push-pull chromophores with diverse new scaffolds. The starting TCPF reacts with bis(N,N-dimethylanilino)acetylene in a formal [2+2] cycloaddition at the exocyclic double bond, followed by retroelectrocyclization, to yield an ethenylene-extended push-pull pentafulvene. The transformation with 4-ethynyl-N,N-dimethylaniline also yields a similar extended pentafulvene as well as two other products that required X-ray analysis for their structure elucidation. One features an 8,8-dicyanoheptafulvene core formed by formal [2+2] cycloaddition, followed by ring opening via fragmentation. The second is a chiral cyclobutenylated tetrahydropentalene, resulting from a cascade of formal [6+2] and [2+2] cycloadditions. All new nonplanar push-pull chromophores display amphoteric redox behavior with both strong electron-donating and -accepting potency. Notably, the N,N-dimethylanilino-substituted extended pentafulvenes show remarkably low oxidation potentials (0.27/0.28 V vs Fc/Fc(+) reference) that are lower than those for N,N-dimethylaniline itself. The push-pull-substituted extended pentafulvenes feature intense electronic absorption bands, extending over the entire visible spectral range into the near infrared, and low highest occupied molecular orbital-lowest unoccupied molecular orbital gaps. These properties, together with high thermal stability and good solubility, suggest the potential use of the new chromophores as advanced materials in molecular electronics devices.


Kv 1.1 is associated with neuronal apoptosis and modulated by protein kinase C in the rat cerebellar granule cell.
Previously, we reported that apoptosis of cerebellar granular neurons induced by low-K+ and serum-free (LK-S) was associated with an increase in the A-type K+ channel current (I(A)), and an elevated expression of main alpha-subunit of the I(A) channel, which is known as Kv4.2 and Kv4.3. Here, we show, as assessed by quantitative RT-PCR and whole-cell recording, that besides Kv4.2 and Kv4.3, Kv1.1 is very important for I(A) channel. The expression of Kv1.1 was elevated in the apoptotic neurons, while silencing Kv1.1 expression by siRNA reduced the I(A) amplitude of the apoptotic neuron, and increased neuron viability. Inhibiting Kv1.1 current by dendrotoxin-K evoked a similar effect of reduction of I(A) amplitude and protection of neurons. Applying a protein kinase C (PKC) activator, phorbol ester acetate A (PMA) mimicked the LK-S-induced neuronal apoptotic effect, enhanced the I(A) amplitude and reduced the granule cell viability. The PKC inhibitor, bisindolylmaleimide I and Gö6976 protected the cell against apoptosis induced by LK-S. After silencing the Kv1.1 gene, the effect of PMA on the residual K+ current was reduced significantly. Quantitative RT-PCR and Western immunoblot techniques revealed that LK-S treatment and PMA increased the level of the expression of Kv1.1, in contrast, bisindolylmaleimide I inhibited Kv1.1 expression. In addition, the activation of the PKC isoform was identified in apoptotic neurons. We thus conclude that in the rat cerebellar granule cell, the I(A) channel associated with apoptotic neurons is encoded mainly by the Kv1.1 gene, and that the PKC pathway promotes neuronal apoptosis by a brief modulation of the I(A) amplitude and a permanent increase in the levels of expression of the Kv1.1 alpha-subunit.


Effectiveness of Acupuncture in Relieving Chemotherapy-induced Leukopenia in Patients With Breast Cancer: A Systematic Review With A Meta-Analysis and Trial Sequential Analysis.
Breast cancer is one of the most common cancers and a major cause of death in women worldwide. Chemotherapy is mainly used to treat and control the progression of breast cancer. Leukopenia is the most common side effect of chemotherapy which may decrease immune function and further lead to serious fatal infections. The purpose of this study was to evaluate the effect of acupuncture on regulating hematopoietic function in chemotherapy-induced leukopenia among patients with breast cancer. PubMed, Embase, Cochrane Library, CINAHL Plus, Web of Science, and Chinese articles in the Airiti Library and China National Knowledge Infrastructure (CNKI) databases were searched to August 2021 for papers to include in a systematic review and meta-analysis. A random-effects model was applied. The effect size was calculated by Hedges' g. Heterogeneity was determined using Cochran's Q test. Moderator analyses were performed to examine potential sources of heterogeneity. A trial sequential analysis (TSA) was conducted to determine whether the current sample size was sufficient. Ten randomized controlled trials involving 650 participants were eligible for inclusion. Analysis by the random-effects model showed a significant effect by acupuncture of ameliorating leukopenia during chemotherapy. Levels of white blood cells (WBCs) were increased (Hedges' g = 0.70, P < .001, I2 = 34%), neutrophil counts (Hedges' g = 0.80, P < .001, I2 = 0%) were significantly enhanced. Moreover, regardless of the manner through which acupuncture was applied, overall values of WBCs increased. The current meta-analysis supports acupuncture possibly ameliorating chemotherapy-induced leukopenia, as WBC and neutrophil values significantly increased after acupuncture in patients undergoing chemotherapy. Additionally, regardless of the type of acupuncture, values of WBCs increased. These findings are actionable and support both the clinical use of acupuncture to relieve chemotherapy-induced leukopenia and further research regarding the use of acupuncture in patients experiencing immunosuppression when undergoing chemotherapy.Trial Registration: PROSPERO-CRD42020215759.


Demineralization and sectioning of human kidney stones: A molecular investigation revealing the spatial heterogeneity of the stone matrix.
The molecular mechanisms by which kidney stones grow are largely unknown. Organic molecules from the urine combine with mineral crystals to form stones, but analysis of the stone matrix has revealed over a thousand different proteins, with no clues as to which are important for stone growth. Molecules that are present in every layer of a stone would be candidates for having an essential function, and thus the analysis of the stone matrix at a microscopic level is necessary. For this purpose, kidney stones were demineralized, sectioned, stained, and imaged by microscopy, using micro CT for precise orientation. Histological staining demonstrated heterogeneity in the density of adjacent layers within stones. Additional results also showed brilliant and unique autofluorescence patterns in decalcified nephroliths, indicating heterogeneous organic composition in adjacent layers. Regions of calcium oxalate (CaOx) stones were dissected using laser microdissection (LMD) for protein analysis. LMD of broad regions of demineralized CaOx stone sections yielded the same proteins as those found in different specimens of pulverized CaOx stones. These innovative methodologies will allow spatial mapping of protein composition within the heterogeneous stone matrix. Proteins that consistently coincide spatially with mineral deposition would be candidates for molecules essential for stone growth. This kind of analysis will be required to assess which of the thousand proteins in the stone matrix may be fundamental for stone growth.