[Heavy metal exposure and reproductive toxicity: Advances in studies].
Heavy metals are among the major pollutants affecting the environment, with a higher density of metal element than that of water and an extensive presence in the natural environment. Trace elements such as zinc, copper, nickel and chromium mediate important physiological functions and metabolic regulation at normal levels, and insufficient intake of them will lead to related diseases. Heavy metals such as cadmium, lead and mercury do not participate in the normal metabolism of the human body and will cause damage to the body even at an extremely low dose. Heavy metal pollution mainly comes from industrial wastewater, fossil fuel combustion, wastewater, smelting, mining, vehicle exhaust, hazardous waste dumping, and fertilizer abuse. Unable to be biodegraded, heavy metals have a long biological half-life in nature, which in turn leads to bio-accumulation and -amplification. Eating contaminated vegetables is one way of being exposed to heavy metals. Heavy metals produce adverse effects not only on the human reproductive system, but also on the fetus by penetrating the placental barrier, and on the hypothalamic-pituitary-gonadal axis as well, consequently affecting sexual maturation and reproductive function. With the sharp increase of heavy metals in the environment, researches on their reproductive toxicity and antagonistic drugs have an important clinical significance.


Subtyping of properdin factor B (Bf) by isoelectrofocusing.
Properdin factor B (Bf) is a polymorphic protein in the human plasma. Two common alleles, BfS, BfF, and two rare alleles, BfF1, BfS1, have been demonstrated in Caucasians. We now report that BfF can be subtyped into two alleles, BfFa and BfFb by isoelectrofocusing. Family studies indicate that they are inherited in a co-dominant pattern. Gene frequencies for Caucasians are: BfS 0.808, BfF1 0.019, BfS1 0.005, BfFa 0.038 and BfFb 0.128.


Lateral sinus reconstructive surgery: treatment of intracranial hypertension by venous anastomosis.
Ten cases of venous by-pass for revascularization of the lateral sinus have been performed to treat intracranial hypertension following hindrance of cerebral venous drainage. Principles and indications of this technique are discussed. In correctly selected cases this technique proved to be efficient in normalizing hypertension of venous origin.


Intraocular twin cysticercosis.
A 20-year-old vegetarian male presented with a history of painful diminution of vision in the right eye for the past month. The patient had dense vitritis. B-scan ultrasonography (USG) revealed two cysts with scolices, one subretinally along with retinal detachment and another one in vitreous cavity. Orbital USG revealed no cystic lesions in the orbit or extraocular muscle. He underwent 23 gauge pars plana vitrectomy. Both intravitreal and subretinal cysts were cut and aspirated using cutter and removed from the eye, and silicon oil was injected. Postoperatively he was started on oral steroids and advised to maintain prone positioning for two weeks. At two months his best corrected visual acuity (BCVA) in the right eye was 20/125 with silicon oil in situ.


Capacitance of the double layer formed at the metal/ionic-conductor interface: how large can it be?
The capacitance of the double layer formed at a metal/ionic-conductor interface can be remarkably large, so that the apparent width of the double layer is as small as 0.3 A. Mean-field theories fail to explain such large capacitance. We propose an alternate theory of the ionic double layer which allows for the binding of discrete ions to their image charges in the metal. We show that at small voltages the capacitance of the double layer is limited only by the weak dipole-dipole repulsion between bound ions, and is therefore very large. At large voltages the depletion of bound ions from one of the capacitor electrodes triggers a collapse of the capacitance to the mean-field value.


Effect of atrial natriuretic peptide on urine flow and glomerular filtration during acute renal allograft rejection.
The effect of exogenous atrial natriuretic peptide (ANP) on urine excretion and glomerular filtration rate (GFR) during acute renal allograft rejection was evaluated in a canine model. Eight animals underwent simultaneous allotransplantation and unilateral native nephrectomy. No preoperative or postoperative immunosuppressive therapy was given. Acute renal function studies were performed on the allografts and companion, native kidneys following surgical exposure and mobilization on the third postoperative day. At reexploration, the allografts were found to be grossly enlarged (138 +/- 10 gm.) and contained moderate-to-marked perivascular interstitial infiltration. Glomerular filtration rate, determined by measurement of urinary inulin clearance, was significantly reduced from prenephrectomy baseline values (19 +/- 4 ml. per minute versus 32 +/- 5 ml. per minute, p < .05). During a 30 minute, intravenous ANP infusion, allograft urine flow rates increased from 1.4 +/- 0.5 ml. per minute to 3.3 +/- 0.4 ml. per minute (p < .01), and GFR increased from 19 +/- 4 ml. per minute to 24 +/- 4 ml. per minute (p < .05). During ANP infusion, mean arterial pressure declined from 136 +/- 7 mm. Hg to 116 +/- 7 mm. Hg (p < .05), and the hematocrit remained unchanged. These observations are consistent with previously described, ameliorative effects of ANP in other models of acute ischemic renal injury and provide an experimental basis for more extended studies examining the potential usefulness of ANP as adjunctive therapy in the treatment of acute renal allograft rejection.


The distribution of the secreted and intracellular forms of plasminogen activator inhibitor 2 (PAI-2) in human peripheral blood monocytes is modulated by serum.
Plasminogen activator inhibitor 2 (PAI-2) is produced by activated monocytes in two forms, intracellular and secreted. We have studied the distribution of these two forms in unstimulated human peripheral blood monocytes and after stimulation by thrombin. Fetal calf serum (FCS) in the culture medium was absolutely necessary for accumulation of intracellular PAI-2; but not for synthesis and secretion. Even at a concentration as low as 0.1%, FCS restored accumulation of intracellular PAI-2. Increasing concentrations of FCS resulted in an increase in the ratio of intracellular to secreted PAI-2. The factor that promoted accumulation of intracellular PAI-2 was not a platelet product. Failure of monocytes to accumulate PAI-2 did not reflect leakage due to cell death, as assessed by LDH in culture supernatants. We propose that accumulation of intracellular PAI-2 is not simply due to poor secretion, but is an active process that is modulated by factor(s) found in serum.


RoseAP: an analytical platform for gene function of Rosa rugosa.
Rosa rugosa, a perennial shrub belonging to family Rosaceae, is a well-known ornamental plant. Its petals contain an abundance of essential oils and anthocyanins with enormous economic and health benefits when used as edible or cosmetic ingredients. The whole genome of R. rugosa was sequenced in 2021, which provided opportunities and challenges for gene regulation. However, many gene functions remain unknown. Therefore, an analytical platform named RoseAP (http://www.gzybioinformatics.cn/RoseAP/index.php) for the functional analysis of R. rugosa genes was constructed. It improved the gene annotation rate by integrating and analyzing genomic and transcriptomic datasets. First, 38,815 genes, covering 97.76% of the coding genes, were annotated functionally and structurally using a variety of algorithms and rules. Second, a total of 33 transcriptome samples were integrated, including 23 samples from our lab and 10 samples from the SRA database. A co-expression network containing approximately 29,657 positive or negative gene pairs, covering 74.7% of the coding genes, was constructed based on PCC and MR algorithms. Network analysis revealed that the DFR function was closely related to anthocyanin metabolism. It demonstrated the reliability of the network. Several SAUR genes of R. rugosa shared similar expression patterns. RoseAP was used to determine the sequence, structure, functional annotation, expression profile, regulatory network, and functional modules at the transcriptional and protein levels by inputting gene IDs. In addition, auxiliary analytical tools, including BLAST, gene set enrichment, orthologue conversion, gene sequence extraction, gene expression value extraction, and JBrowse, were utilized. Regular updates to RoseAP are expected to facilitate mining of gene function and promote genetic improvement in R. rugosa.


Characterization of six textile dyes as fluorescent stains for flow cytometry.
Few fluorescent stains specific for cell constituents other than DNA are available. To assess their potential use as fluorescent stains for flow cytometry, the cell staining specificity of 55 compounds, originally synthesized for use as textile dyes and fluorescent brighteners, was explored and their excitation and emission wavebands determined. From these, six dyes were chosen for more detailed analysis. All six are vital stains, with excitation wavelengths allowing their use with an argon ion laser, and specific for a range of cell structures including mitochondria, Golgi bodies, lipid droplets, nuclear membrane, and endoplasmic reticulum. Concentrations as low as 0.01-0.25 microM were found to be adequate for most purposes, and high background fluorescence was not a problem. Their specificity allows differentiation between non-cycling and cycling cells. The properties of two of the stains allows their combination with propidium iodide or ethidium bromide for simultaneous determination of DNA content profiles. Being vital stains, usable at very low concentrations, and specific for a range of cell organelles, these six stains may be of considerable utility in flow cytofluorometry. We suggest that other textile dyes may be of use in flow cytofluorometry, or that their structures may form a starting point for the synthesis of further fluorescent stains of enhanced specificity.


Generation and absolute reactivity of an aryl enol radical cation in solution.
Laser flash photolysis of 1-bromo-1-(4-methoxyphenyl)acetone in acetonitrile leads to the formation of the alpha-acyl 4-methoxybenzyl radical that under acidic conditions rapidly protonates to give detectable amounts of the radical cation of the enol of 4-methoxyphenylacetone. This enol radical cation is relatively long-lived in acidic acetonitrile (tau approximately equal to 200 micros), which is on the same order of magnitude as the radical cations of other 4-methoxystyrene derivatives. Rate constants for deprotonation of the radical cation and the acid dissociation constant for the enol radical cation were also determined using time-resolved absorption spectroscopy. Deprotonation is rapid, taking place with a rate constant of 3.9 x 10(6) s(-1), but the enol radical cation is found to be only moderately acidic in acetonitrile having a pK(a) = 3.2. The lifetime of the enol radical cation was also found to be sensitive to the presence of oxygen and chloride. The sensitivity toward oxygen is explained by oxygen trapping the vinyloxy radical component of the enol radical cation/vinyloxy equilibrium, while chloride acts as a nucleophile to trap the enol radical cation.


Allergic asthma: An indication for allergen immunotherapy.
. Allergen immunotherapy (AIT) as a validated, disease-modifying treatment is nowadays a widely recommended therapy option for allergic rhinitis and allergic asthma. The registration of allergen extracts used for AIT is based on allergen standardization, dose finding trials, and phase 3 trials proving their efficacy in high-quality, statistically significant randomized clinical trials. Real-world evidence (RWE) studies confirm the clinical relevance of these findings. The most data are available for the treatment of patients suffering from allergic rhinitis. Due to the similar inflammatory mechanisms, allergic rhinitis is often associated with allergic asthma. AIT, which induces tolerance against individual allergens, is the approach to treat the underlying mechanisms of these two interrelated respiratory diseases. Some trials have been published focusing primarily on the effect of AIT on parameters of allergic asthma. Here we give a summary of the evidence for the efficacy of AIT in the indication of allergic asthma.


Implementation and Operational Research: Implementation of Multiple Point-of-Care Testing in 2 HIV Antiretroviral Treatment Clinics in South Africa.
A plethora of point-of-care (POC) tests exist in the HIV and tuberculosis diagnostic pipeline which require rigorous evaluation to ensure performance in the field. The accuracy and feasibility of nurse-operated multidisciplinary-POC testing for HIV antiretroviral therapy (ART) initiation/monitoring was evaluated. Random HIV-positive adult patients presenting at 2 treatment clinics in South Africa for ART initiation/monitoring were consented and enrolled. POCT was performed by a dedicated nurse on a venipuncture specimen; Pima (CD4), HemoCue (hemoglobin), Reflotron (alanine aminotransferase, creatinine), Accutrend (lactate) and compared with laboratory testing. External quality assessment, training, workflow, and errors were assessed. n = 324 enrolled at site1; n = 469 enrolled at site 2. Clinical data on n = 305 participants: 65% (n = 198) female with a mean age of 39.8 (21-61) years; mean age of males 43.2 (26-61) years; 70% of patients required 3 or more POC tests/visit. External quality assessment material was suitable for POCT. CD4, hemoglobin and alanine aminotransferase testing showed good agreement with predicate methodology; creatinine and lactate had increased variability. Pima CD4 misclassified up to 11.6% of patients at 500 cells per microliter and reported 4.3%-6% error rate. A dedicated nurse could perform POCT on 7 patients/day; inclusion of Pima CD4 increased time for testing from 6 to 110 minutes. Transcription error rate was 1%. Nurses can accurately perform multidisciplinary POCT for HIV ART initiation/monitoring. This will however, require a dedicated nurse as current duties will increase if POC is added to workflow. The use of Pima CD4 will increase patients initiated on ART. Connectivity will be central to ensure quality management of results, but overall impact will need to still be addressed.


Effect of acaricides on the activity of glutathione transferases from the parasitic mite Sarcoptes scabiei.
Glutathione transferases (GSTs) are a family of multifunctional enzymes with fundamental roles in cellular detoxication. Here we report the molecular characterization of 3 recombinant GSTs belonging to the mu- and delta-class from the parasitic mite Sarcoptes scabiei. Kinetic constants were determined, and the effect of acaricides, including organothiophosphates, pyrethroid esters, a formamidine, a macrocyclic lactone, an organochlorine as well as a bridged diphenyl acaricide, on the activity of the GSTs were tested using 1-chloro-2,4-dinitrobenzene (CDNB) as model substrate. Our results showed that enzymes from the same class and with high amino acid sequence identity have significantly different kinetic properties. For instance, one mu-class GST lost more than 50% of its activity in the presence of one of the organothiophosphates while the activity of the second mu-class GST was only slightly reduced under identical conditions. Tertiary structure modulations indicated that structural differences were the crucial factor for the different kinetic patterns observed. Genome analysis showed that the two mu-class GSTs are organized in tandem in the S. scabiei genome. Taken together these results show that GSTs might be involved in the metabolism of acaricides in S. scabiei.


Photodissociation dynamics of enolic 1,2-cyclohexanedione at 266, 248, and 193 nm: mechanism and nascent state product distribution of OH.
The photodissociation dynamics of 1,2-cyclohexanedione (CHD), which exists in enolic form in gas phase, is studied using pulsed laser photolysis (LP)-laser induced fluorescence (LIF) "pump-and-probe" technique at room temperature. The nascent state distribution of the OH radical, formed after initial photoexcitation of the molecule to it is (π, π*) and Rydberg states, is determined. The initial (π, π*) and Rydberg states are prepared by excitation with the fourth harmonic output of Nd:YAG (266 nm)/KrF (248 nm) and ArF (193 nm) lasers, respectively. The ro-vibrational distribution of the nascent OH photofragment is measured in collision-free conditions using LIF. The OH fragments are formed in the vibrationally cold state at all the above wavelengths of excitation but differ in rotational state distributions. At 266 nm photolysis, the rotational population of OH shows a curvature in Boltzmann plot, which is fairly described by two types of Boltzmann-like distributions characterized by rotational temperatures of 3100 ± 100 and 900 ± 80 K. However, at 248 nm photolysis, the rotational distribution is described by a single rotational temperature of 950 ± 80 K. The spin-orbit and Λ-doublets ratios of OH fragments formed in the dissociation process are also measured. The average translational energy in the center-of-mass coordinate, partitioned into the photofragment pairs of the OH formation channels, is determined to be 12.5 ± 3.0, 12.7 ± 3.0, and 12.0 ± 3.0 kcal/mol at 266, 248, and 193 nm excitation, respectively. The energy partitioning into various degrees of freedom of products is interpreted with the help of different models, namely, statistical, impulsive, and hybrid models. To understand the nature of the dissociative potential energy surface involved in the OH formation channel, detailed ab initio calculations are performed using configuration interaction-singles (CIS) method. It is proposed that at 266 nm photolysis, the OH fragment is formed from two different excited state structures, one with a strong H bonding, similar to that in the ground state, and another without effective H bonding, whereas, at 248 nm photodissociation, it seems that the OH formation occurs mainly from the excited state, which lacks effective H-bonding. At 193 nm excitation, the initially prepared population in the Rydberg state crosses over to a nearby σ* repulsive state along the C-O bond, from where the dissociation takes place. The exit barrier for the OH dissociation channel is estimated to be 14 kcal/mol. The existence of dynamical constraint due to strong hydrogen bond in the ground state is effectively present in the dissociation process at 266 and somewhat deficient at 248 nm photolysis.


[Clinical features and prognosis in MLL-AF10 positive acute leukemia].
To analyze the clinical features and prognosis of acute leukemia patients with the mixed lineage leukemia(MLL)gene rearrangements AF10 positive. 6 cases with MLL-AF10 positive were analyzed retrospectively, related literatures were reviewed to clarify MLL-AF10 patients'clinical features and prognosis. The median age of 6 cases was 19.5 years old, 5 patients with fever onset, the onset white blood cells of 4 patients were less than 10×10⁹/L. 5 cases were as M₅ and 1 case M₄ according to FAB classification, the level of fusion gene(RQ-PCR)was 0.23%-22.60% when diagnosed, 4 cases had concomitant WT1 gene mutation, flow cytometry disclosed myeloid phenotype. Of 5 evaluated patients achieved the first complete remission after conventional chemotherapy, 2 cases of complex karyotype died, one case died of sepsis in induction, another died from failing of transplantation. 4 out of 5 transplant recipients gained long term survival. The MLL-AF10 positive patients were mostly young men, the majority FAB classification was M5 or M4, often onset with fever, low white blood cells and low level of fusion gene, usually associated with WT1 mutation. Conventional chemotherapy produced a high response rate, but easy to relapse, while the complex karyotype had a poor prognosis, allo-HSCT may have the potential to improve the prognosis of MLL-AF10 positive patients.


HEK293S cells have functional retinoid processing machinery.
Rhodopsin activation is measured by the early receptor current (ERC), a conformation-associated charge motion, in human embryonic kidney cells (HEK293S) expressing opsins. After rhodopsin bleaching in cells loaded with 11-cis-retinal, ERC signals recover in minutes and recurrently over a period of hours by simple dark adaptation, with no added chromophore. The purpose of this study is to investigate the source of ERC signal recovery in these cells. Giant HEK293S cells expressing normal wild-type (WT)-human rod opsin (HEK293S) were regenerated by solubilized 11-cis-retinal, all-trans-retinal, or Vitamin A in darkness. ERCs were elicited by flash photolysis and measured by whole-cell recording. Visible flashes initially elicit bimodal (R(1), R(2)) ERC signals in WT-HEK293S cells loaded with 11-cis-retinal for 40 min or overnight. In contrast, cells regenerated for 40 min with all-trans-retinal or Vitamin A had negative ERCs (R(1)-like) or none at all. After these were placed in the dark overnight, ERCs with outward R(2) signals were recorded the following day. This indicates conversion of loaded Vitamin A or all-trans-retinal into cis-retinaldehyde that regenerated ground-state pigment. 4-butylaniline, an inhibitor of the mammalian retinoid cycle, reversibly suppressed recovery of the outward R(2) component from Vitamin A and 11-cis-retinal-loaded cells. These physiological findings are evidence for the presence of intrinsic retinoid processing machinery in WT-HEK293S cells similar to what occurs in the mammalian eye.


Return of symptoms after discontinuation of clomipramine in patients with obsessive-compulsive disorder.
To evaluate the need for maintenance drug therapy in patients with obsessive-compulsive disorder, the authors assessed 21 patients with obsessive-compulsive disorder who manifested sustained improvement during 5 to 27 months of clomipramine treatment and who agreed to participate in a double-blind discontinuation study. Of 18 patients who completed the study, 16 had substantial recurrence of obsessive-compulsive symptoms by the end of the 7-week placebo period. In addition, 11 had a significant increase in depressive symptoms. Treatment duration before discontinuation of clomipramine was not related to the frequency or severity of obsessive-compulsive or depressive symptom appearance. These findings suggest that prolonged drug treatment may be warranted for obsessive-compulsive disorder.


A Patient with the GLA p.E66Q Mutation Exhibiting Vascular Parkinsonism and Bilateral Pulvinar Lesions.
A 76-year-old man was admitted to our hospital due to gait difficulty. Brain imaging indicated bilateral pulvinar lesions and moderate white matter lesions. The serum α-galactosidase A levels were measured for the differential diagnosis of bilateral pulvinar lesions and were found to be abnormally low. Therefore, the patient was suspected to have variant Fabry disease. A GLA mutation analysis showed the p.E66Q mutation, which is speculated to be a functional polymorphism rather than a disease-causing mutation of Fabry disease. Enzyme replacement therapy did not result in a marked improvement, however, the disease progression stopped.


Planning for effective use of on-line systems.
A perspective of developments in the field of computerized information retrieval is presented, and policies are suggested for the efficient use of on-line systems. Examples of MEDLINE, CHEMCON, AND TOXLINE searches are given with cost data and compared, where possible, with manual searches. The lowest costs were obtained with on-line searching by information scientists. MEDLINE is superior in quality to manual searching of Index Medicus, but on-line searching of Chemical Abstracts keywords is not an effective substitute for manual searching of Chemical Abstracts Substance Indexes.


Bombyx mori prothoracicostatic peptide receptor is allosterically activated via a Gα(i/o)-protein-biased signalling cascade by Drosophila sex peptide.
In insects, molting and metamorphosis are strictly regulated by ecdysteroids. Ecdysteroid synthesis is positively or negatively controlled by several neuropeptides. The prothoracicostatic peptide (PTSP) BmPTSP (Bombyx mori prothoracicostatic peptide), isolated from the larval brain of B. mori, has been demonstrated to inhibit ecdysteroid synthesis in the prothoracic glands (PGs) [Hua et al. (1999) J. Biol. Chem. 274, 31169-31173]. More recently, the newly recognized B. mori receptor for Drosophila melanogaster sex peptide (DmSP) has been identified as a receptor for BmPTSP. However, details on the signalling pathways and physiological functions of this receptor have remained elusive. In the present paper, we report the functional characterization of the BmPTSP receptor (BmPTSPR)/sex peptide (SP) receptor (SPR) using both mammalian and insect cells. Synthetic DmSP shows the potential to inhibit forskolin (FSK) or adipokinetic hormone (AKH)-induced cAMP-response element (CRE)-driven luciferase (Luc) activity in a manner comparable with synthetic BmPTSP1. However, DmSP displayed a much lower activity in triggering Ca²⁺ mobilization and internalization than did BmPTSP1. Additionally, 6-carboxy-fluorescein fluorophore (FAM)-labelled DmSP and BmPTSP3 were found to bind specifically to BmPTSPR/SPR. The binding of FAM-DmSP was displaced by unlabelled DmSP, but not by unlabelled BmPTSP1 and, vice versa, the binding of FAM-BmPTSP3 was blocked by unlabelled BmPTSP3, but not by unlabelled DmSP. Moreover, internalization assays demonstrated that BmPTSP1, but not DmSP, evoked recruitment of the Bombyx non-visual arrestin, Kurtz, to the activated BmPTSPR/SPR in the plasma membrane. This was followed by induction of internalization. This suggests that BmPTSP1 is probably an endogenous ligand specific for BmPTSPR/SPR. We therefore designate this receptor BmPTSPR. In contrast, DmSP is an allosteric agonist that is biased towards Gα(i/o)-dependent cAMP production and away from Ca²⁺ mobilization and arrestin recruitment.


A Sustainable Approach to Fabricating Ag Nanoparticles/PVA Hybrid Nanofiber and Its Catalytic Activity.
Ag nanoparticles were synthesized by using Ficus altissimaBlume leaf extract as a reducing agent at room temperature. The resulting Ag nanoparticles/PVA mixture was employed to create Ag nanoparticles/PVA (polyvinyl alcohol) hybrid nanofibers via an electrospinning technique. The obtained nanofibers were confirmed by means of UV-Vis spectroscopy, The X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and then tested to catalyze KBH₄ reduction of methylene blue (MB). The catalytic results demonstrate that the MB can be reduced completely within 15 min. In addition, the Ag nanoparticles/PVA hybrid nanofibers show reusability for three cycles with no obvious losses in degradation ratio of the MB.


Radiation-induced translational control of gene expression.
Radiation-induced gene expression has long been hypothesized to protect against cell death. Defining this process would provide not only insight into the mechanisms mediating cell survival after radiation exposure, but also a novel source of targets for radiosensitization. However, whereas the radiation-induced gene expression profiles using total cellular mRNA have been generated for cell lines as well as normal tissues, with few exception, the changes in mRNA do not correlate with changes in the corresponding protein. The traditional approach to profiling gene expression, i.e., using total cellular RNA, does not take into account posttranscriptional regulation. In this review, we describe the use of gene expression profiling of polysome-bound RNA to establish that radiation modifies gene expression via translational control. Because changes in polysome-bound mRNA correlate with changes in protein, analysis of the translational profiles provides a unique data set for investigating the mechanisms mediating cellular radioresponse.


Serial measurement of arterial plasma progesterone levels throughout gestation and parturition in individual rats.
Daily blood samples were taken from 6, chronically cannulated, fully conscious rats to measure plasma progesterone levels throughout gestation. Progesterone levels in individual rats fluctuated by up to 28 ng/ml per day, but tended to be consistently higher or lower than the group mean. The accuracy of predicting progesterone levels in individual rats from previous values was examined. Progesterone levels on day 7 of gestation were negatively correlated with foetal weights near term. There was little indication that high progesterone levels at any stage of gestation lead to increased foetal or placental weights. Progesterone levels on day 17 were positively correlated with the number of corpura lutea but there was little relationship between progesterone and either the number or total mass of the placentas. Serial blood samples taken from a second group of 6 rats at 2 hourly intervals showed that the time between the major fall in progesterone levels to below 12 ng/ml and the onset of parturition was relatively constant (varying by only 8 h) despite a 29 h range in the total length of gestation.


Pattern of hereditary renal tubular disorders in Egyptian children.
Hereditary renal tubular disorders (HRTD) represent a group of genetic diseases characterized by disturbances in fluid, electrolyte, and acid-base homeostasis. There is a paucity of studies on pediatric HRTD in Egypt. In this study, we aimed to study the pattern, characteristics, and growth outcome of HRTD at an Egyptian medical center. This study included children from one month to < 18-years of age with HRTD who were diagnosed and followed up at the Pediatric Nephrology Unit of Sohag University Hospital from January 2015 to December 2021. Data on patients` demographics, clinical features, growth profiles, and laboratory characteristics were collected. Fifty-eight children (57% males; 72% parental consanguinity; 60% positive family history) were diagnosed with seven HRTD types. The most commonly encountered disorders were distal renal tubular acidosis (distal renal tubular acidosis [RTA] 27 cases, 46.6%) and Bartter syndrome (16 cases 27.6%). Other identified disorders were Fanconi syndrome (6 cases with cystinosis), isolated proximal RTA (4 cases), nephrogenic diabetes insipidus (3 cases), and one case for each RTA type IV and Gitelman syndrome. The median age at diagnosis was 17 months with a variable diagnostic delay. The most common presenting features were failure to thrive (91.4%), developmental delay (79.3%), and dehydration episodes (72.4%). Most children showed marked improvement in growth parameters in response to appropriate management, except for cases with Fanconi syndrome. Last, only one case (with cystinosis) developed end-stage kidney disease. HRTD (most commonly distal RTA and Bartter syndrome) could be relatively common among Egyptian children, and the diagnosis seems challenging and often delayed.


The origin of mutants.
Nucleic acids are replicated with conspicuous fidelity. Infrequently, however, they undergo changes in sequence, and this process of change (mutation) generates the variability that allows evolution. As the result of studies of bacterial variation, it is now widely believed that mutations arise continuously and without any consideration for their utility. In this paper, we briefly review the source of this idea and then describe some experiments suggesting that cells may have mechanisms for choosing which mutations will occur.


Nano-Rifabutin entrapment within glucan microparticles enhances protection against intracellular Mycobacterium tuberculosis.
Recently, yeast-derived glucan particles (GP) have emerged as novel drug delivery agents that provide for receptor-mediated uptake by phagocytic cells expressing β-glucan receptors. In our previous study, we prepared GP loaded with high payload (40.5 + 1.9%) of rifabutin (RB) nano-particles [(RB-NPs)-GP]. We investigated the anti-mycobacterial efficacy and cellular activation responses within Mycobacterium tuberculosis (M. tuberculosis) infected J774 macrophage cells following exposure to the (RB-NPs)-GP formulation. The exposure was seen to augment a robust innate immune response including the induction of reactive oxygen and nitrogen species, autophagy and apoptosis within M. tuberculosis infected macrophage. Further, the efficacy testing of these particles in murine macrophage exhibited that the (RB-NPs)-GP formulation enhanced the efficacy of RB drug by ∼2.5 fold. The study suggests that the set of innate responses conducive to killing intracellular bacteria evoked by (RB-NPs)-GP play a pivotal role in impeding the intracellular M. tuberculosis survival, resulting in enhanced efficacy of the formulation. Our results establish that the (RB-NPs)-GP formulation not only activate M. tuberculosis infected, immune-suppressed macrophage, but also adds significantly to the efficacy of loaded drug, and thus forms a promising approach that should be explored further as an alternative or adjunct form of TB therapy. Highlights Nano-Rifabutin loaded Glucan microparticles [(RB-NPs)-GP] administered to M. tuberculosis infected macrophage. (RB-NPs)-GP induces appropriate innate immune responses in host macrophage. Mycobactericidal Effect of Rifabutin was markedly enhanced by its nano-entrapment in GP. Intracellular drug delivery supplements the innate response in M. tuberculosis infected macrophage.


Characterization of byproducts originating from hemp oil processing.
Valorization of hemp seed meal, a byproduct of hemp oil processing, was performed by measuring the distribution of nutritional and antinutritional compounds in different hemp seed meal fractions. According to chemical composition, two cotyledon-containing fractions (>180 and <180 μm) were significantly richer in protein (p < 0.05) (41.2% ± 0.04% and 44.4% ± 0.02%, respectively), lipid (15.1% ± 0.02% and 18.6% ± 0.04%, respectively), and sugar content (4.96% ± 0.11% and 3.46% ± 0.08%, respectively) in comparison to the hull-containing fractions (>350 and >250 μm), which were significantly richer in crude fiber content (29.5% ± 0.04% and 21.3% ± 0.03%, respectively). The free radical scavenging capacity (IC50) of fraction extracts increased (p < 0.05) with increasing mean particle size (from 17.18 ± 0.59 to 5.29 ± 0.30 mg/mL). Cannabisin B and N-trans-caffeoyltyramine were the most abundant phenolic compounds in the hull fractions (from 267 ± 15.9 to 287 ± 23.1 mg/kg), while cotyledon fractions had higher content of catechin (from 313 ± 12.4 to 744 ± 22.2 mg/kg) and p-hydroxybenzoic acid (from 124 ± 6.47 to 129 ± 8.56 mg/kg (P < 0.05). Well-balanced ω-6 to ω-3 fatty acid ratio (3:1) was determined in all fractions. Antinutrients (trypsin inhibitors, phytic acid, glucosinolates, and condensed tannins) were mostly located in the cotyledon fractions. These findings indicate that the separation of hemp seed meal into different fractions could be used to concentrate valuable target compounds and consequently facilitate their recovery.


Silica-based branched hollow microfibers as a biomimetic extracellular matrix for promoting tumor cell growth in vitro and in vivo.
A novel scaffold composed of loosely branched hollow silica microfibers that has been proven to be highly biocompatible is proposed for the 3D culture of cancer cells. The MCF-7 cancer cells can grow and proliferate freely inside the scaffold in the form of multicellular spheroids. MCF-7 cancer cells cultured on the current 3D silica scaffold retained significantly more oncological characters than those cultured on the conventional 2D substrate and can serve as in vitro tumor model for studying cancer treatment.


Undergraduate medical education in prepaid health care plan settings.
The authors in this article focus on prepaid health care plan (PHCP) involvement in undergraduate medical education and report the results of two surveys undertaken to determine the extent of such involvement. Additionally, the authors provide a review of published studies that have examined the costs of such training. The survey findings show that current use of PHCPs for educational purposes is distributed throughout all four years of undergraduate medical education and is apparently on the rise. In addition to 26 medical schools reporting formal educational arrangements with health maintenance organizations, 35 other schools indicated that they either planned or were seriously considering such arrangements with PHCPs had ongoing ad hoc arrangements with PHCPs, or attributed their lack of an arrangement to an absence of appropriate opportunities rather than to any conceptual reservations. Three studies represented the extent of the published research that could be identified on the costs of formal undergraduate clinical training in PHCPs. Serious inconsistencies in the methodologies employed in those studies resulted in widely varying and even contradictory findings.


Proteomic characterization of differentially expressed proteins in breast cancer: Expression of hnRNP H1, RKIP and GRP78 is strongly associated with HER-2/neu status.
The human epidermal growth factor receptor type 2 (HER-2/neu) oncoprotein is overexpressed in about 30% of breast cancers and associates with metastatic phenotypes of breast tumours. Dissecting the HER-2/neu-modulated molecules in cancer will be helpful in elucidating the underlying molecular mechanisms of HER-2/neu-driven tumourigenesis. We investigated the differential proteome profiles between microdissected HER-2/neu-positive and -negative tumours and unambiguously identified 21 proteins with diverse biological functions by peptide sequencing and NCBInr database interrogation. Six proteins were up-regulated whereas 15 were down-regulated in the HER-2/neu-positive tumours. Differential expressions of heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1), 78 kDa glucose-regulated protein (GRP78/Bip) and Raf-1 kinase inhibitor protein (RKIP), which have not been previously reported as being linked to HER-2/neu signalling, were further verified. Immunohistochemical staining on tissue microarray sections demonstrated a positive correlation of hnRNP H1 (p = 0.008) and negative correlations of GRP78 and RKIP (p = 0.018 and 0.013, respectively) with HER-2/neu. Heregulin α1 enhanced hnRNP H1, but reduced GRP78 and RKIP expression in BT474 cells in a dose-dependent manner, providing evidence of crosstalk between HER-2/neu signalling and these modulators. Our studies have identified novel modulators that are likely to be intricately involved in HER-2/neu-driven tumour proliferation, invasion and metastasis.


Respiratory consequences of intra-abdominal hypertension.
Intra-abdominal hypertension (IAH) is a common complication in critically ill patients that may lead to multiorgan failure and is associated to worse outcome. Respiratory failure is among the most important consequences of IAH and it is originated by different mechanisms, such as chest wall elastance increase, functional residual capacity reduction, compression atelectasis and lung edema formation through reduction in lymphatic drainage. Many experimental studies showed that total lung capacity and functional residual capacity can be decreased by 40% during abdominal hypertension, while respiratory system and chest wall pressure-volume curves can be significantly shifted downward and to the right. Moreover, the relationship between intra-abdominal volume and airway pressure has been found to be exponential, meaning that small increases in volume can translate in dramatic increases in pressure. Clinical studies confirmed relevant atelectasis in dependent lung regions during IAH, with significant reductions in functional residual capacity and compromised oxygenation. Moreover, sepsis-related capillary leak and fluid overload may aggravate IAH and respiratory failure, thus establishing a dangerous vicious circle. Respiratory management of patients with IAH is challenging and there is no univocal answer. The measurement of intra-abdominal pressure and esophageal pressure (as a surrogate of pleural pressure) may be useful in assessing the condition and guiding mechanical ventilation. Positive end-expiratory pressure (PEEP) must be carefully selected to counteract IAH-related diaphragm displacement, but too high PEEP levels are associated with hemodynamic failure. Continuous negative extra-abdominal pressure is a promising approach, but its clinical application needs more investigation.


[Pelvic actinomycosis abscess and intrauterine device].
A case of association between IUD and a left tubal actinomycotic abscess is presented. The 45 year old patient was wearing an IUD for five years. The symptomatology was mainly that of pelvic pain with an associated mass in the left iliac fossa. The working diagnosis was that of a digestive tumor or an adnexal mass. The surgical procedure allowed to identify an inflammatory reaction with a pseudotumoral abscess formation in the left fallopian tube. The etiology was confirmed by the pathology and bacteriology reports. Treatment consists in surgical extirpation of the infected structures and long term antibacterial therapy. Actinomycosis is a rare but potentially serious pelvic disease. It may involve various organs and readily takes on the aspect of tumor formation.


Metachronal waves in concentrations of swimming Turbatrix aceti nematodes and an oscillator chain model for their coordinated motions.
At high concentration, free swimming nematodes known as vinegar eels (Turbatrix aceti), collectively exhibit metachronal waves near a boundary. We find that the frequency of the collective traveling wave is lower than that of the freely swimming organisms. We explore models based on a chain of oscillators with nearest-neighbor interactions that inhibit oscillator phase velocity. The phase of each oscillator represents the phase of the motion of the eel's head back and forth about its mean position. A strongly interacting directed chain model mimicking steric repulsion between organisms robustly gives traveling wave states and can approximately match the observed wavelength and oscillation frequency of the observed traveling wave. We predict body shapes assuming that waves propagate down the eel body at a constant speed. The phase oscillator model that impedes eel head overlaps also reduces close interactions throughout the eel bodies.


Mouse Memory CD8 T Cell Subsets Defined by Tissue-Resident Memory Integrin Expression Exhibit Distinct Metabolic Profiles.
Tissue-resident memory CD8 T cells (TRM) principally reside in peripheral nonlymphoid tissues, such as lung and skin, and confer protection against a variety of illnesses ranging from infections to cancers. The functions of different memory CD8 T cell subsets have been linked with distinct metabolic pathways and differ from other CD8 T cell subsets. For example, skin-derived memory T cells undergo fatty acid oxidation and oxidative phosphorylation to a greater degree than circulating memory and naive cells. Lung TRMs defined by the cell-surface expression of integrins exist as distinct subsets that differ in gene expression and function. We hypothesize that TRM subsets with different integrin profiles will use unique metabolic programs. To test this, differential expression and pathway analysis were conducted on RNA sequencing datasets from mouse lung TRMs yielding significant differences related to metabolism. Next, metabolic models were constructed, and the predictions were interrogated using functional metabolite uptake assays. The levels of oxidative phosphorylation, mitochondrial mass, and neutral lipids were measured. Furthermore, to investigate the potential relationships to TRM development, T cell differentiation studies were conducted in vitro with varying concentrations of metabolites. These demonstrated that lipid conditions impact T cell survival, and that glucose concentration impacts the expression of canonical TRM marker CD49a, with no effect on central memory-like T cell marker CCR7. In summary, it is demonstrated that mouse resident memory T cell subsets defined by integrin expression in the lung have unique metabolic profiles, and that nutrient abundance can alter differentiation.


[Effect of axillary lymph node status on prognosis of different types of invasive breast cancer].
Objective: To investigate the effect of axillary lymph node status on the prognosis of different types of invasive breast cancer. Methods: Patients with invasive breast cancer of different molecular subtypes diagnosed in the breast cancer prevention and treatment center of Beijing Cancer Hospital from January 2000 to July 2011 were collected as a historical cohort, and the influence of lymph node status on the prognosis of different types of breast cancer was analyzed. Results: A total of 4 269 female breast cancer patients with molecular subtypes [aged (50.8±11.2) years] information and 3 824 female breast cancer patients with complete axillary lymph node status information [aged (50.5±10.9) years] were included in the study, including 3 135 cases with both molecular subtypes and lymph node status information. The 10-year event free survival (EFS) rates of hormone receptor (HR)+/human epidermal growth factor receptor-2(HER2)-, HR-/HER2-and HER2+were 82.2%, 79.0% and 76.8%, respectively; the 10-year overall survival (OS) rates were 88.1%, 83.1% and 84.4%, respectively, and the differences of 3 molecular subtypes in EFS and OS were statistically significant (both P<0.001). The 10-year EFS rate of lymph node positive and negative patients was 68.8% and 88.2%, respectively; the 10-year OS rate was 76.7% and 92.5%, respectively, and the differences of lymph node status in EFS and OS were statistically significant (both P<0.001). In lymph node negative subgroup, 3 subtypes showed similar EFS and OS rate (both P>0.05); In lymph node positive subgroup, 3 subtypes showed significantly different EFS and OS (both P<0.05). No modification effect was detected of lymph node status on the correlation of molecular subtypes and EFS, DDFS and OS(all Pinteractive>0.1). Conclusions: Different molecular subtypes of breast cancer have different prognosis. Compared with molecular subtype, lymph node status may be a more important prognostic factor.


Using Healthcare Data in Embedded Pragmatic Clinical Trials among People Living with Dementia and Their Caregivers: State of the Art.
Embedded pragmatic clinical trials (ePCTs) are embedded in healthcare systems as well as their data environments. For people living with dementia (PLWD), settings of care can be different from the general population and involve additional people whose information is also important. The ePCT designs have the opportunity to leverage data that becomes available through the normal delivery of care. They may be particularly valuable in Alzheimer's disease and Alzheimer's disease-related dementia (AD/ADRD), given the complexity of case identification and the diversity of care settings. Grounded in the objectives of the Data and Technical Core of the newly established National Institute on Aging Imbedded Pragmatic Alzheimer's Disease and AD-Related Dementias Clinical Trials Collaboratory (IMPACT Collaboratory), this article summarizes the state of the art in using existing data sources (eg, Medicare claims, electronic health records) in AD/ADRD ePCTs and approaches to integrating them in real-world settings. J Am Geriatr Soc 68:S49-S54, 2020.


Electrophysiologic monitoring during surgery to repair the thoracoabdominal aorta.
The repair of aneurysms and dissections that involve the thoracoabdominal aorta represent a major stress to the cardiovascular surgery team because of the feared complication of paraplegia. Here, the etiology of this complication is explained through a description of the relevant surgical anatomy and characteristics of hemodynamic support. In addition, recent advances in the neurophysiologic assessment of the descending motor pathways and their application to perioperative monitoring are discussed.


Design and implementation of monitoring programmes for internal exposure (project OMINEX).
The costs of monitoring for internal exposure in the workplace are usually significantly greater than the equivalent costs for external exposure. Therefore, there is a need to ensure that resources are employed with maximum effectiveness. The EC-funded OMINEX (optimisation of monitoring for internal exposure) project is developing methods for optimising the design and implementation of internal exposure monitoring programmes. Current monitoring programmes are being critically reviewed, the major sources of uncertainty in assessed internal dose investigated, and guidance formulated on factors such as programme design, choice of method/techniques, monitoring intervals, and monitoring frequency. OMINEX will promote a common, harmonised approach to the design and implementation of internal dose monitoring programmes throughout the EU.


Ibuprofen in the treatment of postoperative pain in small children. A randomized double-blind-placebo controlled parallel group study.
The efficacy of ibuprofen as a pre-emptive analgesic for postoperative pain was investigated in 81 children in the age between one and four years subjected to elective surgery. The patients were randomized into two groups receiving rectally either ibuprofen 40 mg.kg-1.d-1, divided into four equal doses, or placebo in a double blind manner. Additional pain relief was provided by morphine. In the recovery room ibuprofen provided superior pain relief during the first hour and significantly reduced the need of morphine. Heart rate and arterial blood pressure were lower in children who received ibuprofen, probably reflecting better analgesia. The side effects were mild and similar in both groups. We conclude that rectal ibuprofen is a safe analgesic in children in the age between 1 and 4 years and reduces the need of opioids for postoperative pain relief.


Accuracy of Echocardiography to Estimate Pulmonary Artery Pressures With Exercise: A Simultaneous Invasive-Noninvasive Comparison.
Exercise echocardiography is often applied as a noninvasive strategy to screen for abnormal pulmonary hemodynamic response, but it is technically challenging, and limited data exist regarding its accuracy to estimate pulmonary arterial pressure during exercise. Among 65 patients with exertional intolerance undergoing upright invasive exercise testing, tricuspid regurgitation (TR) Doppler estimates and invasive measurement of pulmonary arterial pressure at rest and peak exercise were simultaneously obtained. TR Doppler envelopes were assessed for quality. Correlation, Bland-Altman, and receiver-operating characteristic curve analyses were performed to evaluate agreement and diagnostic accuracy. Mean age was 62±13 years, and 31% were male. High-quality (grade A) TR Doppler was present in 68% at rest and 34% at peak exercise. For grade A TR signals, echocardiographic measures of systolic pulmonary arterial pressure correlated reasonably well with invasive measurement at rest (r=0.72, P<0.001; bias, -2.9±8.0 mm Hg) and peak exercise (r=0.75, P<0.001; bias, -1.9±15.6 mm Hg). Lower quality TR signals (grade B and C) correlated poorly with invasive measurements overall. In patients with grade A TR signals, mean pulmonary arterial pressure-to-workload ratio at a threshold of 1.4 mm Hg/10 W was able to identify abnormal pulmonary hemodynamic response during exercise (>3.0 mm Hg/L per minute increase), with 91% sensitivity and 82% specificity (area under the curve, 0.90; 95% confidence interval, 0.77-1.0; P=0.001). Agreement between echocardiographic and invasive measures of pulmonary pressures during upright exercise is good among the subset of patients with high-quality TR Doppler signal. While the limits of agreement are broad, our results suggest that in those patients, sensitivity is adequate to screen for abnormal pulmonary hemodynamic response during exercise.


Foundational Nutrition: Implications for Human Health.
Human nutrition, and what can be considered "ideal" nutrition, is a complex, multi-faceted topic which many researchers and practitioners deliberate. While some attest that basic human nutrition is relatively understood, it is undeniable that a global nutritional problem persists. Many countries struggle with malnutrition or caloric deficits, while others encounter difficulties with caloric overconsumption and micronutrient deficiencies. A multitude of factors contribute to this global problem. Limitations to the current scope of the recommended daily allowances (RDAs) and dietary reference intakes (DRIs), changes in soil quality, and reductions in nutrient density are just a few of these factors. In this article, we propose a new, working approach towards human nutrition designated "Foundational Nutrition". This nutritional lens combines a whole food approach in conjunction with micronutrients and other nutrients critical for optimal human health with special consideration given to the human gut microbiome and overall gut health. Together, this a synergistic approach which addresses vital components in nutrition that enhances the bioavailability of nutrients and to potentiate a bioactive effect.


Snapshots of Postsynthetic Modification in a Layered Metal-Organic Framework: Isometric Linker Exchange and Adaptive Linker Installation.
Terminal ligand exchange and framework linker exchange have been frequently practiced as powerful tools to functionalize reticular structures such as metal-organic frameworks (MOFs). Herein, we report the postsynthetic modification (PSM) of a 6-connected layered MOF (hxl topology) to achieve a 12-connected fcu framework. In the PSM process, isometric linker exchange in the layers and linker installation between adjacent layers by the substitution of modulating ligands happen simultaneously. Snapshots of PSM at different time points reveal that the hxl domain is adaptively reorganized to create sites for new linker installation, and gradually the fcu domain dominates the crystal. Detailed kinetic analysis suggests that, although adaptive linker installation requires interlayer expansion of stackings in situ, it is kinetically faster than isometric linker exchange in the layers.


Immunosuppression in patients with severe acute pancreatitis.
In severe acute pancreatitis (SAP), immunologic impairment in the early phase may be linked to subsequent infectious complications. In this study, immunologic alterations in patients with SAP were analyzed, and immunologic parameters related to infectious complications were clarified. A total of 101 patients with SAP were analyzed retrospectively. Various immunologic parameters on admission were analyzed and compared between the infection group and noninfection group during SAP. Furthermore, chronologic change in the lymphocyte count was investigated, and its utility for predicting infection was compared with conventional scoring systems. Serum immunoglobulin G (IgG), serum IgM, lymphokine-activated killer cell activity, and natural killer cell activity were low, and the incidence of abnormally low values was 50.0%, 65.0%, 45.5%, and 42.4%, respectively. Serum complement factor 3 was significantly negatively correlated with the APACHE II score. The lymphocyte count was decreased below the normal range, and was significantly negatively correlated with the APACHE II score. CD4-, CD8-, and CD20-positive lymphocyte counts were below the normal range, and CD4- and CD8-positive lymphocyte counts were significantly lower in the infection group. The lymphocyte count on day 14 after admission was significantly lower in the infection group and was more useful for predicting infection than conventional scoring systems. Immunosuppression occurs from the early phase in SAP, and quantitative impairment of lymphocytes, mainly T lymphocytes, may be closely related to infectious complications during SAP. CD4- and CD8-positive lymphocyte counts on admission and the lymphocyte count on day 14 after admission may be useful for predicting infection.


Temperature-sensitive heparin-modified poloxamer hydrogel with affinity to KGF facilitate the morphologic and functional recovery of the injured rat uterus.
Endometrial injury usually results in intrauterine adhesion (IUA), which is an important cause of infertility and recurrent miscarriage in reproductive women. There is still lack of an effective therapeutic strategy to prevent occurrence of IUA. Keratinocyte growth factor (KGF) is a potent repair factor for epithelial tissues. Here, a temperature-sensitive heparin-modified poloxamer (HP) hydrogel with affinity to KGF (KGF-HP) was used as a support matrix to prevent IUA and deliver KGF. The rheology of KGF-HP hydrogel was carefully characterized. The cold KGF-HP solution was rapidly transited to hydrogel with suitable storage modulus (G') and loss modulus (G″) for the applications of uterus cavity at temperature of 33 °C. In vitro release demonstrated that KGF was released from HP hydrogels in sustained release manner for a long time. In vivo bioluminescence imaging showed that KGF-HP hydrogel was able to prolong the retention of the encapsulated KGF in injured uterus of rat model. Moreover, the morphology and function of the injured uterus were significantly recovered after administration of KGF-HP hydrogel, which were evaluated by two-dimensional ultrasound imaging and receptive fertility. Not only proliferation of endometrial glandular epithelial cells and luminal epithelial cells but also angiogenesis of injured uterus were observed by Ki67 and CD31 staining after 7 d of treatment with KGF-HP hydrogel. Finally, a close relatively relationship between autophagy and proliferation of endometrial epithelial cells (EEC) and angiogenesis was firstly confirmed by detecting expression of LC3-II and P62 after KGF treatment. Overall, KGF-HP may be used as a promising candidate for IUA treatment.


[Analysis of the model binding site of anti-2,4-dichlophenoxyacetic acid antibodies].
Models of three-dimensional structures of Fv domains of three antibodies specific to the pesticide 2,4-dichlorophenoxyacetic acid (2,4-D) have been derived from the sequence data by comparative modeling. The same binding site cavities were observed in all cases. The most important residue in antigen binding is tyrosine, which serves as a wall of cavity and putatively forms pi-stacking interaction with aromatic moiety of the ligand. Another cavity wall is formed by hydrophobic residues. At the entrance of cavity a glutamate residue is located in 2 of 3 structures. Docking of 2,4-D and its analogs on the models was performed. On the basis of docking results an experimental cross-reactivity data were qualitatively explained. Using results of the modeling, mutation of glutamate to serine or lysine was suggested to eliminate electrostatic repulsion between antibody and ligand and to improve 2,4-D binding efficiency. Target mutations in the antibody binding site were checked on the model.


One-carbon metabolism factors and leukocyte telomere length.
Dietary and genetic factors involved in the one-carbon metabolism pathway may affect telomere length through DNA methylation and synthesis, but this has not been comprehensively investigated in epidemiologic studies. We cross-sectionally examined associations between dietary and genetic factors in the one-carbon metabolism pathway and relative peripheral blood leukocyte telomere length. A total of 1715 participants from the Nurses' Health Study (NHS) had measurements of relative telomere length and plasma concentrations of folate, vitamin B-6, vitamin B-12, cysteine, and homocysteine. Food-frequency questionnaire (FFQ) measurements were also used for the assessment of folate, choline, methionine, riboflavin, vitamin B-6, vitamin B-12, and alcohol intakes. Genotyping was performed on 475 participants with telomere measurements on 29 mostly nonsynonymous single-nucleotide polymorphisms (SNPs) involved in one-carbon metabolism. Unconditional logistic and linear regression models were used. There were no significant dose-response relations between any plasma- or FFQ-measured dietary factors and relative telomere length in multivariate analyses. For folate, vitamin B-6, and vitamin B-12, results from the use of FFQ data were consistent with plasma-biomarker findings. We showed no significant associations that involved SNPs and relative telomere length after we accounted for the false discovery rate. Our analyses involving plasma and questionnaire measurements of one-carbon metabolism factors show that some key dietary and genetic factors in this metabolic network are not associated with relative peripheral blood leukocyte telomere length.


A dynamic pressure view cell for acoustic stimulation of fluids--Micro-bubble generation and fluid movement in porous media.
The development and baseline operation of an acoustic view cell for observing fluids, and fluid-fluid and fluid-solid interfaces in porous media over the frequency range of 10-5000 Hz is described. This range includes the industrially relevant frequency range 500-5000 Hz that is not covered by existing devices. Pressure waveforms of arbitrary shape are generated in a 17.46 mm ID by 200 mm and 690.5 mm long glass tubes at flow rates up to 200 ml/min using a syringe pump. Peak-to-peak amplitudes exceeding 80 kPa are readily realized at frequencies from 10 to 5000 Hz in bubble free fluids when actuated with 20 Vpp as exemplified using castor oil. At resonant frequencies, peak-to-peak pressure amplitudes exceeding 500 kPa were obtained (castor oil at 2100 Hz when actuated with 20 Vpp). Impacts of vibration on macroscopic liquid-liquid and liquid-vapour interfaces and interface movement are illustrated. Pressure wave transmission and attenuation in a fluid saturated porous medium, randomly packed 250-330 μm spherical silica beads, is also demonstrated. Attenuation differences and frequency shifts in resonant peaks are used to detect the presence and generation of dispersed micro-bubbles (<180 μm diameter), and bubbles within porous media that are not readily visualized. Envisioned applications include assessment of the impacts of vibration on reaction, mass transfer, and flow/flow pattern outcomes. This knowledge will inform laboratory and pilot scale process studies, where nuisance vibrations may affect the interpretation of process outcomes, and large scale or in situ processes in aquifers or hydrocarbon reservoirs where imposed vibration may be deployed to improve aspects of process performance. Future work will include miscible interface observation and quantitative measurements in the bulk and in porous media where the roles of micro-bubbles comprise subjects of special interest.


Synthesis and characterization of Ag-polymer nanocomposites.
We report the synthesis of Ag nanoparticles in polyethylene terephthalate (PET) matrix using atom beam co-sputtering. Metal filling factor was evaluated by Rutherford backscattering spectrometry. Microstructural evolutions of the nanocomposites films were investigated by transmission electron microscopy, which confirmed the formation of irregular shaped Ag nanoparticles. The X-ray photoelectron spectroscopy measurements of the sputter deposited PET film and co-sputtered deposited Ag-PET as well as PET bulk foil (from Goodfellows) were performed to study chemical composition of the nanocomposite films. The optical properties of these nanocomposites were studied by light absorption/transmission, which revealed a narrow transmission of UV light approximately 320 nm and a broad surface plasmon resonance absorption extending up to infrared region (approximately 2400 nm). Swift heavy ion irradiation of Ag-PET nanocomposite resulted in narrowing the full width at half maximum of transmission band.


Death process of primitive erythrocytes and phagocytosis by liver macrophages of the mouse embryo.
Primitive erythrocytes from the yolk sac are nucleated cells which have a short life span of several days in the embryonic circulation of the mouse. The death process of primitive erythrocytes was ultrastructurally investigated in embryonic mice. At 12 days of gestation, primitive erythrocytes accounted for 96.1% of the circulating erythrocytes. The percentages in 13-, 14-, 15- and 18-day-embryos were 43.8%, 15.4%, 7.7% and 0.0%, respectively. Between 13 and 15 days, anucleate primitive erythrocytes made up from 1.5% to 5.9% of circulating erythrocytes. During the gestational period, the nuclei of primitive erythrocytes markedly decreased in volume, and the chromatin underwent condensation and marginated to crescents along the nuclear envelope. Following nuclear fragmentation and dissolution of condensed chromatin, nuclear residues were finally formed in aging primitive erythrocytes. Formation of annulate lamellae was also observed, associated with the nuclear shrinkage. The nuclei had an apoptotic-like appearance, but TUNEL-positive reactions could not be identified in any nuclei of the primitive erythrocytes. Dying erythrocytes with nuclear residues were phagocytosed in toto by hepatic macrophages and disposed of from embryonic circulation without enucleation.


Losartan has no additive effect on the response to heavy-resistance exercise in human elderly skeletal muscle.
Our purpose here was to investigate the potential of blocking the angiotensin II type I receptor (AT1R) on the hypertrophy response of elderly human skeletal muscle to 4 mo of heavy-resistance exercise training. Fifty-eight healthy elderly men (+65 yr) were randomized into three groups, consuming either AT1R blocker (losartan, 100 mg/day) or placebo for 4 mo. Two groups performed resistance training (RT) and were treated with either losartan or placebo, and one group did not train but was treated with losartan. Quadriceps muscle biopsies, MR scans, and strength tests were performed at baseline and after 8 and 16 wk. Biopsies were sectioned for immunohistochemistry to determine the number of satellite cells, capillaries, fiber type distribution, and fiber area. Gene expression levels of myostatin, connective tissue, and myogenic signaling pathways were determined by real-time RT-PCR. Four months of heavy-resistance training led in both training groups to expected improvements in quadriceps (∼3-4%) and vastus lateralis (∼5-6%), cross-sectional area, and type II fiber area (∼10-18%), as well as dynamic (∼13%) and isometric (∼19%) quadriceps peak force, but with absolutely no effect of losartan on these outcomes. Furthermore, no changes were seen in satellite cell number with training, and most gene targets failed to show any changes induced by training or losartan treatment. We conclude that there does not appear to be any effect of AT1R blocking in elderly men during 4 mo of resistance training. Therefore, we do not find any support for using AT1R blockers for promoting muscle adaptation to training in humans. NEW & NOTEWORTHY Animal studies have suggested that blocking angiotensin II type I receptor (AT1R) enhances muscle regeneration and prevents disuse atrophy, but studies in humans are limited. Focusing on hypertrophy, satellite cells, and gene expression, we found that AT1R blocking did not result in any greater responses with 4 mo of resistance training. These results do not support previous findings and question the value of blocking AT1R in the context of preserving aging human muscle.


Activation of human factor VII by factors IXa and Xa on human bladder carcinoma cells.
Single chain factor VII is converted by limited proteolysis to its activated form, factor VIIa, by a number of blood coagulation proteases including factor IXa and factor Xa. We have determined the relative rate of human factor VII activation by human factors IXa and Xa in two different systems: one containing Ca++ and human bladder carcinoma (J82) cells, and the other containing Ca++ and mixed brain phospholipids. The rate of factor VII activation was determined by a one stage coagulation assay, and proteolytic cleavage of factor VII was assessed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting techniques. On a molar basis, factor Xa was sixfold more efficient than factor IXa beta in activating factor VII when the activation reaction occurs on J82 cell surfaces. In contrast, when incubation takes place in a suspension of mixed phospholipids, factor Xa was 18-fold more efficient in activating factor VII than factor IXa beta. In addition, factor IXa alpha activated factor VII at a rate approximately one-half that observed using factor IXa beta. In the absence of cells or phospholipids, no activation of factor VII by either factors IXa or Xa was observed. The addition of stoichiometric amounts of either recombinant human factor VIII (des B-domain) or plasma-derived factor VIIIa failed to augment the rate of factor VII activation by either factors IXa alpha or IXa beta. Likewise, purified human factor Va failed to influence the rate of factor VII activation by factor Xa in either system. Collectively, our studies reveal that J82 cells possess procoagulant phospholipid capable of readily supporting the activation of factor VII by either factors IXa beta or Xa. Our data also demonstrate that the relative ability of factor IXa beta and Xa to activate factor VII is significantly different when these reactions occur on tumor cell surfaces as compared with suspensions of mixed phospholipids.


7-prenyloxi-6-methoxycoumarin from Polygala sabulosa A.W. Bennett Regulates p38 MAPK and NF-kB Pathways Inhibiting the Inflammation Induced by Carrageenan in the Mouse Model of Pleurisy.
Polygala sabulosa, popularly known as "timutu-pinheirinho," has been used in Brazilian folk medicine for the treatment of bowel and kidney disorders and as an expectorant. Evaluate the anti-inflammatory effects of the crude extract (CE), acetonic fraction (Ac), and the main compound, 7-prenyloxi-6-methoxycoumarin (PC) on a mouse model of carrageenan-induced pleurisy. A mouse model of carrageenan-induced pleurisy was used to investigate the effects of P. sabulosa CE, Ac and PC on leukocyte migration, exudate formation, activities of myeloperoxidase (MPO), and adenosine-deaminase (ADA), levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and nitric oxide (NO). In addition, the effect of the plant material on lung histology was also evaluated. The effects of PC on the TNF-α, IL-1β and NO synthase 2 (NOS2) mRNA expression, were also investigated. Finally, the effect of PC on the nuclear factor-kappa B (NF-κB) and p38 mitogen-activated protein kinase (p38 MAPK) was also evaluated. CE, Ac and PC reduced inflammation in the pleural cavity and lungs. This effect was evidenced by reduction on all inflammatory parameters evaluated; the exception being the inability of the CE to inhibit exudate formation. In isolation, PC showed reduction on mRNA levels of TNF-α, IL-1β and NOS2, and on activation of the NF-κB and p38 MAPK pathways. The presented results show that P. sabulosa has significant anti-inflammatory activity, as does its main compound, PC. Moreover, the results suggest that PC exerts its effects mainly by inhibited the NF-κB and p38 MAPK pathways.


Chum-RNA allows preparation of a high-quality cDNA library from a single-cell quantity of mRNA without PCR amplification.
Linear RNA amplification using T7 RNA polymerase is useful in genome-wide analysis of gene expression using DNA microarrays, but exponential amplification using polymerase chain reaction (PCR) is still required for cDNA library preparation from single-cell quantities of RNA. We have designed a small RNA molecule called chum-RNA that has enabled us to prepare a single-cell cDNA library after four rounds of T7-based linear amplification, without using PCR amplification. Chum-RNA drove cDNA synthesis from only 0.49 femtograms of mRNA (730 mRNA molecules) as a substrate, a quantity that corresponds to a minor population of mRNA molecules in a single mammalian cell. Analysis of the independent cDNA clone of this library (6.6 x 10(5) cfu) suggests that 30-fold RNA amplification occurred in each round of the amplification process. The size distribution and representation of mRNAs in the resulting one-cell cDNA library retained its similarity to that of the million-cell cDNA library. The use of chum-RNA might also facilitate reactions involving other DNA/RNA modifying enzymes whose Michaelis constant (K(m)) values are around 1 mM, allowing them to be activated in the presence of only small quantities of substrate.


[Variety regulation of aloe-emodin-3-CH2-O-beta-D-glucopyranoside and emodin-8-O-beta-D-glucopyranoside in five processed pieces from Rheum palmatum].
To compare the contents of two another anthraquinone-O-glucosides in five different processed products from Rheum palmatum. Aloe-emodin-3-CH2-O-beta-D-glucopyranoside and emodin-8-O-beta-D-glucopyranoside were determined simultaneously by HPLC on an Agilent TC-C18 (2) column at 35 degrees C with the tetrahydrofuran-1% glacial acetic acid (25:75). The detection wavelength was set at 410 nm and the flow rate was 0.9 mL x min(-1). The calibration curves for two components were linear within the range of 0.0090-0.2704 microg (r = 0.9996), 0.0396-1.188 microg (r = 0.9996), and the average recoveries were 97.85%, 97.19% respectively. The results showed the remarkable variation regulations among the five different processed pieces. The contents of the crude pieces and the pieces roasted vinegar were almost the same, while the pieces roasted with millet wine were a little higher than that of the crude pieces, and the contents at the two components in prepared pieces and charring pieces evidently reduced.


Differential expression of antimicrobial peptides in human fungal keratitis.
To analyze a series of antimicrobial peptides (AMPs) in corneal tissue from individuals with fungal keratitis (FK) during the active phase of the fungus infection and after healing. Patients undergone lamellar keratoplasty for the treatment of severe FK or corneal scar had their corneal buttons sampled. Quantitative real-time polymerase chain reaction (PCR) was used to ascertain the gene expression of human beta-defensin (HBD)-1, -2, -3, -9, S100A7, 8, 9, and LL-37. All AMPs' messenger ribonucleic acid (mRNA) expression was considerably elevated in all samples (n=12). In contrast to controls, where HBD-2, -3, and S100A7 mRNAs were expressed at very low levels, it was discovered that HBD-1, -9, S100A8, S100A9, and LL-37 were constitutively expressed in all healed samples (n=4). HBD-1, -2 -3, S100A7, and LL-37 mRNAs were significantly increased in all active FK samples (n=8). The levels of HBD-9, S100A8, and S100A9 mRNAs were moderately upregulated in all active FK samples. Subgroup comparison showed that HBD-2 was significantly increased in Fusarium keratitis samples (n=5), and LL-37 mRNAs were significantly enhanced in Aspergillus keratitis samples (n=3). Whereas there was not significantly increased of HBD-1, -3, -9, S100A7, 8, 9 mRNA in Aspergillus keratitis samples compared with Fusarium keratitis samples. AMPs expression is increased in active FK, but not all AMPs are equally expressed. HBD-2 and LL-37 expression levels are the highest, showing some specificity of AMP expression related to FK. Human AMPs, particularly HBD-2 may play a significant role in Fusarium keratitis and LL-37 might be the key player in Aspergillus keratitis.


Recent advances in the study of testicular nuclear receptor 4.
Testicular nuclear receptor 4 (TR4), also known as NR2C2 (nuclear receptor subfamily 2, group C, member 2), is a transcriptional factor and a member of the nuclear receptor family. TR4 was initially cloned from human and rat hypothalamus, prostate, and testes libraries. For almost two decades, its specific tissue distribution, genomic organization, and chromosomal assignment have been well investigated in humans and animals. However, it has been very difficult to study TR4's physiological functions due to a lack of specific ligands. Gene knock-out animal techniques provide an alternative approach for defining the biological functions of TR4. In vivo studies of TR4 gene knockout mice (TR4(-/-)) found that they display severe spinal curvature, subfertility, premature aging, and prostate prostatic intraepithelial neoplasia (PIN) development. Upstream modulators, downstream target gene regulation, feedback mechanisms, and differential modulation mediated by the recruitment of other nuclear receptors and coregulators have been identified in studies using the TR4(-/-) phenotype. With the establishment of a tissue-specific TR4(-/-) mouse model, research on TR4 will be more convenient in the future.


Correlation between portal vein anatomy and bile duct variation in 407 living liver donors.
Our aim was to determine whether variant bile duct (BD) anatomy is associated with portal vein (PV) and/or hepatic artery (HA) anatomy. We examined the associations between BD anatomy and PV and/or HA anatomy in 407 living donor transplantation donors. We also examined whether the right posterior BD (RPBD) course was associated with the PV and/or HA anatomy. Variant PV, HA and BD anatomies were found in 11%, 25% and 25%, respectively, of 407 donors enrolled in this study. The presence of a variant BD was more frequently associated with a variant PV than with a normal PV (61% vs. 20%, p < 0.0001). By contrast, the presence of a variant HA was not associated with a variant BD. A supraportal RPBD was found in 357 donors (88%) and an infraportal RPBD was found in 50 donors (12%). An infraportal RPBD was significantly more common in donors with a variant PV than in donors with a normal PV (30% vs. 10%, p = 0.0004). Variant PV, but not variant HA, anatomies were frequently associated with variant BD anatomy. Additionally, an infraportal RPBD was more common in donors with a variant PV than in donors with a normal PV.


Perinatal Outcomes and Influence of Amniotic Fluid Volume Following Previable, Preterm Prelabor Rupture of Membranes (pPPROM): A Historical Cohort Study.
To determine perinatal outcomes and influence of amniotic fluid volume in pregnancies complicated by previable, preterm prelabor rupture of membranes (pPPROM). This was a historical cohort study from two tertiary-level maternity hospitals (January 1, 2009 to December 31, 2015). All pregnancies complicated by pPPROM were identified using ICD coding of discharge abstracts. Hospital charts were reviewed to collect maternal demographics, pregnancy and delivery events, and immediate postnatal outcomes (including survival). Post-processing review of stored ultrasound images was performed to evaluate the relationship between amniotic fluid volume and outcomes. A total of 113 pregnancies were eligible and 99 were included in the final analysis (74 with "expectant management" and 25 opting for elective termination). The median gestational age at pPPROM was 20+6 weeks [IQR 19+4 to 21+5]. For those choosing expectant management, the median latency between pPPROM and delivery was 7 days, median gestational at delivery was 23+1 weeks, and neonatal survival to discharge was 27.5% overall. There was a trend towards higher rates of pregnancy termination at one hospital (31.7%) compared to the other (15.4%), but no difference between sites with respect to latency, mode of delivery, or survival amongst those managed expectantly. There was a relationship between survival and gestational age at pPPROM (p<0.04), as well as initial amniotic fluid volume category: 52.6% of survivors had normal initial amniotic fluid volumes whereas the majority of previable losses had oligohydramnios and the majority of stillbirths had anhydramnios. After expectant management, more than one in four newborns following pPPROM survived to hospital discharge. While gestational age at rupture was most strongly correlated with survival, normal initial amniotic fluid volumes were mostly seen in survivors whereas stillbirths more frequently had anhydramnios. These findings will help to improve counseling and care of patients with pPPROM and in guiding long-term follow-up studies.


PDCD1 strengthens the sensitivity of ovarian cancer to cisplatin chemotherapy by promoting apoptosis.
The primary purpose of this study was to make clear the role of PDCD1 in the occurrence and progression of ovarian cancer, and explain its mechanism. RT-PCR, westem blot, MTT and immunohistochemistry were used to detect the expression levels of PDCD1 mRNA and protein in human ovarian cancer cell lines (SKOV3, 3AO, CAOV3 and OVCAR3), human normal ovary, serous cystadenoma, and serous cystadenocarcinoma tissue. SKOV3, SKOV3-MOCK, and SKOV3-PDCD1 cells were subcutaneously injected into the armpit of nude mice to observe the effect of PDCD1 expression on tumorigenic ability. Cisplatin, carboplatin, cyclophosphamide, etoposide and paclitaxel were used in the experiments. PDCD1 was lowly expressed in SKOV3 and 3AO, moderately expressed in CAOV3, and highly expressed in OVCAR3. PDCD1 significantly inhibited the proliferation and clone formation ability of the ovarian carcinoma cell line SKOV3. In the SKOV3-PDCD1 group, the tumor formation rate decreased significantly and the tumor formation time prolonged significantly. The CAOV3 and OVCAR3 cells with high expression of PDCD1 were more sensitive to cisplatin. The SKOV3 and 3AO cells with low expression of PDCD1 were less sensitive to cisplatin. Compared with the SKOV3- MOCK control group, the apoptosis rate and the expression levels of the caspase-3/8 proteins activity increased significantly in the PDCD1 overexpression group. The expression levels of caspase-9 and Bax increased slightly. No significant changes were observed in the expression of Bcl-2. The expression of PDCD1 decreased significantly in human ovarian cancer. Overexpression of PDCD1 can inhibit the proliferation capacity of ovarian cancer. PDCD1 strengthens the sensitivity of ovarian cancer to cisplatin by promoting cisplatin-induced apoptosis.


[Anticholinergic therapy of urinary incontinence and urinary frequency associated with the elderly--with special reference to dementia].
Pharmacotherapy with anticholinergic agents was studied in a total of 80 patients aged 65 years or older with chief complaints of urinary frequency (4 patients) and/or ugency incontinence (76 patients). The subjects were 45 men and 35 women at the age ranging between 65 and 92 (mean 73.7). The patients received anticholinergic agents (terodiline hydrochloride 24 mg/day, oxybutynin hydrochloride 6 mg/day, propantheline bromide 60 mg/day separately or in combination) for more than two weeks. Subjective symptoms and objective findings were assessed before and after the administration. In addition, according to the result of Hasegawa's dementia rating scale the patients were divided into dementia group and non-dementia group for further evaluation of the study drugs. As a result, cystometrogram revealed significant increase of maximum bladder capacity in either dementia group or non-dementia group. There was no significant difference in rate of objective improvement between both groups. On the other hand, rate of subjective improvement was significantly higher in non-dementia group (40%) than in dementia group (15%). As mentioned above, improvement of cystometrogram findings was not associated with improvement of subjective symptoms in the demented patients. This suggests that the major cause of incontinence in demented patients is not the bladder dysfunction but the specific conditions of demented patients such as agnosia and apraxia.


High-grade prostatic intraepithelial neoplasia.
High-grade prostatic intraepithelial neoplasia is considered the most likely precursor of prostatic carcinoma. The only method of detection is biopsy; prostatic intraepithelial neoplasia (PIN) does not significantly elevate serum prostate-specific antigen concentration and cannot be detected by ultra-sonography. The incidence of PIN in prostate biopsies averages 9% (range, 4%-16%), representing 115,000 new cases of PIN diagnosed each year in United States. PIN has a high predictive value as a marker for adenocarcinoma, and its identification warrants repeated biopsy for concurrent or subsequent invasive carcinoma. Carcinoma will develop in most patients with PIN within 10 years. PIN is associated with progressive abnormalities of phenotype and genotype that are intermediate between normal prostatic epithelium and cancer, indicating impairment of cell differentiation and regulatory control with advancing stages of prostatic carcinogenesis. Androgen deprivation therapy decreases the prevalence and extent of PIN, suggesting that this form of treatment may play a role in chemoprevention.


Persistent organic pollutants and metals in the freshwater biota of the Canadian Subarctic and Arctic: an overview.
Over 1999-2002, an extensive series of contaminant studies was conducted on freshwater biota of Canada's Arctic and Subarctic regions. The majority of inorganic contaminant studies focused on mercury and fish. While mercury concentrations were low in benthic feeding fish such as whitefish, predatory fish such as lake trout, pike, and walleye frequently had mercury levels which exceeded 0.2 mug/g, the consumption guideline for frequent consumers of fish, and 0.5 microg/g, the guideline for the commercial use of fish. Numerous consumption advisories were issued for lakes along the Mackenzie River. Relatively high mercury levels appear to be due to a combination of relatively old fish populations (because of light fishing pressures) and tend to be more prevalent in smaller lakes where warmer summer water temperatures and watershed influences result in greater mercury and methyl mercury inputs. Mercury levels were substantially lower in char than in lake trout, possibly due to a combination of a less fish-rich diet, a colder environment, and smaller MeHg watershed inputs. Less research has been conducted on other metals but some, such as rubidium, show pronounced variations in concentration that may be related to geological influences. Temporal trend monitoring has revealed little evidence of declining mercury levels in fish that can be attributed to declining atmospheric inputs. Because mercury follows complex pathways in the environment, other factors may operate to counteract reductions in atmospheric mercury sources, e.g., climatic variability, changes in the commercial fishery, and interactions between fish species. Most organochlorine (OC) investigations were based on long term trend monitoring and focused on char (Cornwallis Island), burbot (Great Slave Lake, Yukon lakes, Slave River at Fort Smith, Mackenzie River at Fort Good Hope) and lake trout (Yukon lakes, Great Slave Lake). There was strong evidence of declining OC concentrations in char, particularly SigmaHCH and Sigmachlordane, which may reflect a response to declining atmospheric inputs. Endosulfan concentrations increased, as in the atmosphere. There also was evidence of declining OC concentrations in burbot in the Slave and Mackenzie rivers but not in Great Slave Lake and Yukon lakes. OC concentrations decreased in lake trout in Yukon lakes in the 2000s, most probably because of changes in the fish themselves (i.e., reduced lipid content, condition factor) and possibly climatic variability. Similarly, OCs declined in Great Slave Lake trout. New research on PDBEs and perfluorinated compounds determined that these contaminants are widespread in freshwater fish and concentrations may be increasing. Global warming is a major issue of concern for Arctic and Subarctic waters and may have adverse impacts on contaminant levels in fish and other biota. There is a need for contaminant studies in the north to be broadened to investigate climatic effects. In addition, monitoring studies should be broadened to consider factors affecting other aspects of fish biology. Foremost among these is integrating contaminant monitoring studies on lakes such as Lake Laberge and Great Slave Lake with stock assessment studies. Ecosystem based studies should be conducted on Great Slave Lake and Lake Laberge to more effectively understand contaminant trends and should consider inputs (atmospheric, river inflow, resupension), losses (sedimentation, volatilization), and biological pathways.


Macrophage depletion using Cytodex.
Cytodex (microcarrier) beads were adapted for use as an adhering surface to deplete macrophages from a mouse spleen cell population. Non-adherent cells recovered from the incubation of one mouse spleen with 50 mg of Cytodex showed good viability and had markedly reduced proliferative response to the T cell mitogens phytohemagglutinin and concanavalin A. Response to lipopolysaccharide was, however, less clearly affected. Peritoneal exudate cells, and adherent cells recovered from the Cytodex by trypsinization, were able to restore the mitogenic response of non-adherent cells.


Tracking the evolution of 3D gene organization demonstrates its connection to phenotypic divergence.
It has recently been shown that the organization of genes in eukaryotic genomes, and specifically in 3D, is strongly related to gene expression and function and partially conserved between organisms. However, previous studies of 3D genomic organization analyzed each organism independently from others. Here, we propose an approach for unified inter-organismal analysis of gene organization based on a network representation of Hi-C data. We define and detect four classes of spatially co-evolving orthologous modules (SCOMs), i.e. gene families that co-evolve in their 3D organization, based on patterns of divergence and conservation of distances. We demonstrate our methodology on Hi-C data from Saccharomyces cerevisiae and Schizosaccharomyces pombe, and identify, among others, modules relating to RNA splicing machinery and chromatin silencing by small RNA which are central to S. pombe's lifestyle. Our results emphasize the importance of 3D genomic organization in eukaryotes and suggest that the evolutionary mechanisms that shape gene organization affect the organism fitness and phenotypes. The proposed algorithms can be utilized in future studies of genome evolution and comparative analysis of spatial genomic organization in different tissues, conditions and single cells.


[Activities of hepatic ATP-citrate lyase and acetyl CoA carboxylase in herbivorous voles and C57BL/6J mice].
Activities of hepatic ATP-citrate lyase and acetyl CoA carboxylase, lipogenetic key enzymes, were measured in herbivorous voles and C57BL/6J mice. Hepatic ATP citrate lyase and acetyl CoA carboxylase activities in voles were very low, under one fifth and one half of those in C57BL/6J mice, respectively. It is considered to be one of characteristics as a herbivore that hepatic lipogenetic ability in voles is considerably low as compared to that in mice.


[Barley chromosome identification using genomic in situ hybridization in the genome of backcrossed progeny of barley-wheat amphiploids [H. geniculatum All. (2n = 28) x T. aestivum L. (2n = 42)] (2n = 70)].
Genomic in situ hybridization (GISH) has been used to study characteristics of the formation of alloplasmic lines detected among self-pollinated backcrossed progeny (BC1F5-BC1F8) of barley--wheat amphiploids [Hordeum geniculatum All. (2n = 28) x Triticum aestivum L. (2n = 42)] (2n = 70). The chromosome material of the wild barley H. geniculatum has been shown to contribute to these lines. For example, fifth-generation plants (BC1F5) had genotypes (2n = 42w + 2g), (2n = 42w + 1g + 1tg), and (2n = 41w + 1g), where w is common wheat chromosomes, g is barley (H. geniculatum) chromosomes, and tg is the telocentric chromosome of wild barley. Beginning from the BC1F6 generation, alloplasmic telocentric addition lines (2n = 42 + 2tg) and (2n = 42 + 1tg) appear. This lines has been found cytogenetically unstable. The progeny of each of these cytological types include not only the (2n = 42 + 2tg) and (2n = 42 + 2tg) addition plants, but also plants with the monosomic (2n = 41 + 1tg) and the disomic (2n = 40 + 2tg) substitutions, as well as the (2n = 41 + 2tg) plants, which lack one wheat chromosome and have two telocentric barley chromosomes. It has been demonstrated that the selection for well-filled grains favors the segregation of telocentric addition lines (2n = 42 = 2tg) and (2n = = 42 + 1tg).


ApoE genotype, past adult lead exposure, and neurobehavioral function.
Our objective in this study was to determine if the known relation between tibia bone lead levels and neurobehavioral test scores are influenced by the apolipoprotein E (ApoE) genotype. We collected data on 20 neurobehavioral tests in 529 former organolead workers who had an average of 16 years since last occupational exposure to lead. We used linear regression to model the relations between each of 20 neurobehavioral test scores and tibia lead, a binary variable for ApoE genotype (i.e., at least one Epsilon4 allele vs. none), and an interaction term between tibia lead and the binary term for ApoE genotype. At the time of testing, former lead workers were an average of 57.6 years of age; 82% were younger than 65 years. In regression analysis, we observed one statistically significant and one borderline significant coefficient for ApoE genotype alone. Coefficients for the ApoE and tibia lead interaction term were negative in 19 of the 20 regression models. This indicates that the slope for the relation between tibia lead and each neurobehavioral test was more negative for individuals with at least one Epsilon4 allele than for those who did not have an Epsilon4 allele. Four of 19 negative coefficients for the interaction term were statistically significant (digit symbol, Purdue pegboard assembly, Purdue pegboard-dominant hand, complex reaction time); another three of the remaining 16 coefficients (symbol digit, trail-making A, Stroop) were borderline significant (i.e., p < 0.10). This study suggests that individuals may vary in susceptibility to the long-term effects of lead on the central nervous system (CNS). In particular, the persistent CNS effect of lead may be more toxic in individuals who have at least one ApoE-Epsilon4 allele.


Recurrent splinter haemorrhages weeks after a tick bite.
A 52-year-old man developed fever, headache, tinnitus, and painful joints. He reported a tick bite contracted during a summer holiday in the Netherlands, followed by erythema on his left arm three weeks earlier. Initial treatment with doxycycline had failed and he had now developed signs of meningoencephalitis. Laboratory tests showed an increased white cell count (16.1 x 10(9)/1), and elevated ESR (51/1h).


Knockdown of PGC1α suppresses dysplastic oral keratinocytes proliferation through reprogramming energy metabolism.
Oral potentially malignant disorders (OPMDs) are precursors of oral squamous cell carcinoma (OSCC). Deregulated cellular energy metabolism is a critical hallmark of cancer cells. Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC1α) plays vital role in mitochondrial energy metabolism. However, the molecular mechanism of PGC1α on OPMDs progression is less unclear. Therefore, we investigated the effects of knockdown PGC1α on human dysplastic oral keratinocytes (DOKs) comprehensively, including cell proliferation, cell cycle, apoptosis, xenograft tumor, mitochondrial DNA (mtDNA), mitochondrial electron transport chain complexes (ETC), reactive oxygen species (ROS), oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and glucose uptake. We found that knockdown PGC1α significantly inhibited the proliferation of DOKs in vitro and tumor growth in vivo, induced S-phase arrest, and suppressed PI3K/Akt signaling pathway without affecting cell apoptosis. Mechanistically, downregulated of PGC1α decreased mtDNA, ETC, and OCR, while enhancing ROS, glucose uptake, ECAR, and glycolysis by regulating lactate dehydrogenase A (LDHA). Moreover, SR18292 (an inhibitor of PGC1α) induced oxidative phosphorylation dysfunction of DOKs and declined DOK xenograft tumor progression. Thus, our work suggests that PGC1α plays a crucial role in cell proliferation by reprograming energy metabolism and interfering with energy metabolism, acting as a potential therapeutic target for OPMDs.


Hydroxyapatite-reactive salivary protein revealed by iso-electrofocusing electrophoresis.
Salivary protein involvement in the formation of acquired enamel pellicle, so far, has been discussed in terms of hydroxyapatite (HA)-reactive salivary proteins only from the parotid gland. This study was undertaken to seek this type of protein in the human whole (mixed) saliva and to investigate its normal and pathological variations. Several kinds of hydroxyapatite, either biogenous or synthesized by solid phase reaction, were used as a powder (250 mesh). HA was incubated with concentrated whole saliva at 25 degrees for 30 min. After centrifugation and filtration salivary proteins were analysed on a Multiphor isoelectrofocusing gel electrophoresis. The control salivary proteins were separated into three major groups; acidic (A1-A8), neutral neutral (N1-N4), and basic (B1-B3) isoelectric point (pI). In the HA incubated sample, one of the major neutral bands (NI) preferentially disappeared at about pI 7.5. This NI band was missing or scarce in the parotid saliva and had an amino acid composition rich in glycine, lysine, serine, glutamic acid, aspartic acid, and histidine. This protein was considered to be one of the major HA-reactive proteins in human whole saliva.