Secretion of insulin-like growth factors and their binding proteins by human normal and hyperplastic prostatic cells in primary culture.
Benign prostatic hyperplasia (BPH) is the most common benign proliferative disorder of unknown etiology found in men. Because insulin-like growth factors (IGFs) with their binding proteins (IGFBPs) are involved in the control of cellular proliferation, differentiation, and metabolism, we compared their secretion by prostatic epithelial and stromal cells in primary culture from the four different zones of normal prostate and from hyperplastic tissue to assess their contributions to the hyperplastic development. IGF-I could not be detected in the conditioned medium from either epithelial or stromal cells from normal and BPH tissues. IGF-II concentrations were the same in the conditioned medium from the epithelial cells of the different zones of the normal prostate and that of BPH cells. IGF-II concentrations secreted in stromal cell culture medium, however, were higher in the periurethral zone than in the peripheral and central zones. Moreover, in the periurethral zone, stromal cells secreted higher concentrations of IGF-II than did epithelial cells. Also, BPH stromal cells secreted more IGF-II than did BPH epithelial cells. IGFBP-3, IGFBP-2, and IGFBP-4 were all secreted by both epithelial and stromal cells. In contrast, IGFBP-5 was only produced by stromal cells of the periurethral zone of the normal prostate and BPH tissue. IGFBP-3 was predominantly secreted by normal stromal cells of the transitional zone. We observed that BPH stromal cells presented the same pattern of IGF-II and IGFBP production as normal stromal cells of the periurethral zone. These data support the hypothesis that the periurethral zone is the main region of the prostate implicated in the development of BPH. They also suggest that the variability in both IGF-II secretion and the secreted forms of IGFBPs, depending on anatomical location within the organ, may be important for the autocrine regulation of normal and hyperplastic prostate growth.


Efficacy and safety of fluoride varnishes.
Clinical studies show that fluoride varnishes, such as Duraphat, are effective in increasing the fluoride content in the enamel and preventing caries. Varnish application is fast and easy. A professional prophylaxis before varnish application is not necessary, which decreases the application time. Patients receive significant preventive benefits with only semiannual varnish applications. Finally, and most importantly, studies show that fluoride varnishes are safe. Effectiveness, application ease, and safety give fluoride varnishes an advantage over other types of topical fluoride treatments, such as gels and rinses.


[Sequential pacing following cardiopulmonary bypass].
Twenty patients with combined mitral valve disease were studied to evaluate whether the mode of cardiac pacing can influence myocardial performance after cardiopulmonary bypass. All patients underwent the same surgical procedure (mitral-valve-replacement) under standardized anaesthetic procedure. After weaning from extracorporeal circulation the following haemodynamic measurements were performed either under ventricular pacing or under sequential ("physiological") pacing: blood-pressure (radial artery), central venous pressure (CVP, jugular vein), cardiac output (as cardiac index, C. I.), pulmonary artery pressure (PAP) using Swan-Ganz-thermodilution catheter (jugular vein) and left atrial pressure (LAP). All patients were investigated as well under ventricular pacing as under sequential pacing (heart rate: 90 X min-1; AV-delay: 200 msec; stimulation with a pacemaker Medtronics 5330). Compared with the situation under ventricular pacing the haemodynamic parameters changed, when sequential pacing was applied: arterial pressure and cardiac output increased, whereas CVP as well as PAP and LAP decreased. The data indicate that there is some influence on cardiac work by the mode of pacing. Physiological pacing compared to ventricular pacing seems to lead to a marked improvement in cardiac performance. Particularly patients with severe dysrhythmia following cardiopulmonary bypass should be treated by physiological (sequential) pacing.


[Comparative study on water-induced micronuclei and chromosomal aberrations in human embryonic lung fibroblast cells].
The paper reported the induction of micronuclei (MN) and structural chromosomal aberration (SCA) in human embryonic lung fibroblast cell (KMB) by water supply. The correlation of SCA and MN, NDI and MI was also reported. The organic extracts of both source and drinking water could induce the SCA and MN formation at different doses. NDI and MI decreased with the increase of sample doses (r = -0.904 and -0.980 in source water and r = -0.882 and -0.918 in drinking water, respectively). These data suggested a good correlation between chromosome damage as measured by MNBN and aberrant cells and cytotoxicity as measured by NDI and MI. Correlation coefficients of source and drinking water were 0.886, 0.958, 0.994 and 0.960 respectively.


Toll-Like Receptor- and Protein Kinase R-Induced Type I Interferon Sustains Infection of Leishmania donovani in Macrophages.
Leishmania donovani is a protozoan parasite that causes visceral leishmaniasis, provoking liver and spleen tissue destruction that is lethal unless treated. The parasite replicates in macrophages and modulates host microbicidal responses. We have previously reported that neutrophil elastase (NE) is required to sustain L. donovani intracellular growth in macrophages through the induction of interferon beta (IFN-β). Here, we show that the gene expression of IFN-β by infected macrophages was reduced by half when TLR4 was blocked by pre-treatment with neutralizing antibodies or in macrophages from tlr2-/- mice, while the levels in macrophages from myd88-/- mice were comparable to those from wild-type C57BL/6 mice. The neutralization of TLR4 in tlr2-/- macrophages completely abolished induction of IFN-β gene expression upon parasite infection, indicating an additive role for both TLRs. Induction of type I interferon (IFN-I), OASL2, SOD1, and IL10 gene expression by L. donovani was completely abolished in macrophages from NE knock-out mice (ela2-/-) or from protein kinase R (PKR) knock-out mice (pkr-/-), and in C57BL/6 macrophages infected with transgenic L. donovani expressing the inhibitor of serine peptidase 2 (ISP2). Parasite intracellular growth was impaired in pkr-/- macrophages but was fully restored by the addition of exogenous IFN-β, and parasite burdens were reduced in the spleen of pkr-/- mice at 7 days, as compared to the 129Sv/Ev background mice. Furthermore, parasites were unable to grow in macrophages lacking TLR3, which correlated with lack of IFN-I gene expression. Thus, L. donovani engages innate responses in infected macrophages via TLR2, TLR4, and TLR3, via downstream PKR, to induce the expression of pro-survival genes in the host cell, and guarantee parasite intracellular development.


Enzyme-based antigen localization and quantitation in cell and tissue samples (Midwestern assay).
Quantitation of antigen concentration in cell and tissue samples typically requires antigen extraction, which precludes antigen localization in the same sample. Similarly, antigen immunolocalization in fixed cells or tissue sections provides limited information about antigen concentration. We have developed a rapid and sensitive assay for simultaneous antigen localization and quantitation in cell and tissue samples that does not involve antigen extraction, radioactive materials, or image analysis. Fixed cells and/or tissue sections are used with antigen-specific enzyme-linked probes to generate soluble reaction products that are spectrophotometrically quantifiable and deposited reaction products that are microscopically localizable. The amount of soluble reaction product is dependent on several variables, including antigen concentration, probe specificity and sensitivity, sample size, and enzyme reaction time. These variables can be experimentally controlled so that soluble reaction product is proportional to antigen concentration in the sample. This assay was used in multiple applications including detection of Ki-67 nuclear antigen immunoreactivity in human brain tumors, in which it showed a clear relationship with visually determined Ki-67 cell labeling indexes. This assay, termed the Midwestern assay, should be applicable to a wide variety of antigens in both clinical and research samples.


A swellable polymer as carbamazepine dissolution rate enhancer.
A superdisintegrant (cross-linked sodium carboxymethylcellulose, Ac-Di-Sol was used for the enhancement of the dissolution rate of carbamazepine, an anti-epileptic drug characterized by very low water solubility. Three different drug/polymer systems were prepared: a physical mixture and two loaded systems obtained using a solvent evaporation method and a spraying method. In vitro dissolution tests showed that the dissolution rate in water of carbamazepine from all the systems prepared (compared with that of the pure drug) always increases, particularly in the case of the physical mixture and of the loaded system obtained with the spraying method, while DSC analysis shows that no drug amorphisation has occurred.


Tensile Strength and Moisture Absorption of Sugar Palm-Polyvinyl Butyral Laminated Composites.
Natural fiber reinforced composites have had a great impact on the development of eco-friendly industrial products for several engineering applications. Sugar palm fiber (SPF) is one of the newly found natural fibers with limited experimental investigation. In the present work, sugar palm fiber was employed as the natural fiber reinforcement. The composites were hot compressed with polyvinyl butyral (PVB) to form the structure of laminated composites and then were subjected to tensile testing and moisture absorption. The maximum modulus and tensile strength of 0.84 MPa and 1.59 MPa were registered for samples PVB 80-S and PVB 70-S, respectively. Subsequently, the latter exhibited the highest tensile strain at a maximum load of 356.91%. The moisture absorption test revealed that the samples exhibited better water resistance as the proportion of PVB increased relative to the proportion of SPF due to the remarkable hydrophobic property of PVB in comparison with that of SPF.


Neuropsychological performance, mood, and complaints of cognitive and motor difficulties in individuals infected with the human immunodeficiency virus.
Seventy-nine military medical beneficiaries infected with human immunodeficiency virus (HIV+) and 27 HIV-seronegative control subjects (HIV-) completed a neuropsychological evaluation and a semistructured interview inquiring about difficulties in function. More HIV+ than HIV- subjects reported difficulties. HIV+ subjects reporting difficulties were significantly more likely to be deficient on attention, response speed, motor function, and memory than those not reporting difficulties. Findings for early-stage HIV+ subjects were similar. HIV+ individuals who complained of difficulties reported depression and anxiety symptoms significantly more frequently than those who did not complain, but these symptoms were not related to neuropsychological performance. Complaints of difficulties by HIV+ individuals may reflect either actual neuropsychological deficiency or mood disturbance, but the effects of each appear to be independent.


Super-Resolution Three-Dimensional Imaging of Actin Filaments in Cultured Cells and the Brain via Expansion Microscopy.
Actin is an essential protein in almost all life forms. It mediates diverse biological functions, ranging from controlling the shape of cells and cell movements to cargo transport and the formation of synaptic connections. Multiple diseases are closely related to the dysfunction of actin or actin-related proteins. Despite the biological importance of actin, super-resolution imaging of it in tissue is still challenging, as it forms very dense networks in almost all cells inside the tissue. In this work, we demonstrate multiplexed super-resolution volumetric imaging of actin in both cultured cells and mouse brain slices via expansion microscopy (ExM). By introducing a simple labeling process, which enables the anchoring of an actin probe, phalloidin, to a swellable hydrogel, the multiplexed ExM imaging of actin filaments was achieved. We first showed that this technique could visualize the nanoscale details of actin filament organizations in cultured cells. Then, we applied this technique to mouse brain slices and visualized diverse actin organizations, such as the parallel actin filaments along the long axis of dendrites and dense actin structures in postsynaptic spines. We examined the postsynaptic spines in the mouse brain and showed that the organizations of actin filaments are highly diverse. This technique, which enables the high-throughput 60 nm resolution imaging of actin filaments and other proteins in cultured cells and thick tissue slices, would be a useful tool to study the organization of actin filaments in diverse biological circumstances and how they change under pathological conditions.


Maturation of the ventilatory response to CO2 in the newborn piglet.
In 12 piglets aged 0 to 1.5 d, we assessed the contribution of the peripheral and central chemoreceptors in mediating the ventilatory response to CO2 and the apneic threshold during normoxia (arterial O2 tension, 13 kPa) using the dynamic end-tidal forcing technique. With this technique, the ventilatory response is separated into a peripheral and a central component using a two-compartment model. Each component is described by a CO2 sensitivity, a time constant, a transport delay time, and an apneic threshold. The means of the estimated parameters per piglet were compared with those obtained in a previous study in piglets aged 2 to 11 d (Wolsink JG, Berkenbosch A, DeGoede J, Olievier CN: J Physiol (Lond) 456:39-48, 1992). The ratio of the peripheral CO2 sensitivity to the total CO2 sensitivity was found to be significantly lower in the younger group of piglets (0.14 +/- 0.10 versus 0.29 +/- 0.10), whereas the apneic threshold was significantly higher (2.52 +/- 1.12 kPa versus 1.06 +/- 1.46 kPa). We conclude that the peripheral chemoreceptors are responsive to CO2 shortly after birth. However, the ventilatory response to CO2 maturates in the first few days after birth by an increase in the relative contribution of the peripheral chemoreceptors to the total ventilatory response and a decreasing apneic threshold.


Effects of recovery modes after knee extensor muscles eccentric contractions.
This study aimed to evaluate the benefit of using low-intensity running or electromyostimulation (EMS) to hasten the recovery process from eccentric-contraction-induced injury. Before and 30 min, 24 h, 48 h, and 96 h after a one-legged downhill run, electrical stimulations were applied to the femoral nerve of healthy volunteers. Superimposed twitches were delivered during isometric maximal voluntary contraction (MVC) to determine the voluntary activation level (%VA). For 4 d after the exercise, each subject performed either (i) 30 min of running at 50% VO2max, (ii) 30 min of low-frequency EMS on the lower limb extensor muscles, or (iii) passive recovery. Recovery time courses of the different variables did not differ significantly among the three experimental conditions. MVC decreased 30 min after the exercise and did not recover thereafter (P < 0.001). Percent VA was depressed after the exercise (P < 0.05) but did not contribute to MVC decrement thereafter. Mechanical responses to 80- and 20-Hz stimulation (P80 and P20, respectively) were significantly reduced over time (P < 0.01 and P < 0.001, respectively). Interestingly, MVC, P20, and P80 decrements were not statistically different (-9.6 +/- 14.5%, -13.2 +/- 14.2%, and -12.3 +/- 11.3%, respectively) at 48 h, and the P20.P80(-1) ratio showed complete recovery at this time. The different recovery modes had no significant effect on the recovery time course of contractile properties. The prolonged torque loss is mainly due to peripheral alterations. Our results suggest that an alteration of the excitation-contraction coupling might be involved during the first 2 d after the eccentric exercise. From 2 to 4 d, damage to force-generating structures could account for the remaining torque deficit.


Dissecting the mechanism of carotid atherosclerosis from the perspective of regulation.
Carotid atherosclerosis is a chronic inflammatory disease of the arterial wall. The present study aimed to identify changes in the gene expression and regulatory factors for atherosclerotic plaques of carotid atherosclerosis from an early to an advanced stage. The original data were downloaded from the NCBI GEO database under accession no. GSE28829. Differentially expressed genes (DEGs) were detected by the Robust Multiarray Average (RMA). The enriched Gene Ontology (GO) terms and pathways for DEGs using DAVID were subsequently identified. The transcriptional and microRNA (miRNA) regulatory network were constructed for the DEGs. Cis-regulatory signals were also investigated. More genes were activated in the advanced stage compared with the early stage. IGHG1 and SPP1 were upregulated, while MYBL1 and PLD were downregulated. The upregulated genes in the advanced stage were involved in atherosclerosis‑related GO terms such as immune, vascular and cell movement homeostasis. The DEGs were significantly enriched in cell adhesion molecules (CAMs) and the focal adhesion pathway. MMP9 and CFL2 played key roles in the transcriptional regulatory network. Moreover, miR-328 was identified as one of the hubs in the miRNA regulatory network. The results may therefore be used to determine the mechanism involved in carotid atherosclerosis.


Binding of anti-inflammatory alpha-melanocyte-stimulating-hormone peptides and proinflammatory cytokines to receptors on melanoma cells.
alpha-Melanocyte-stimulating hormone (alpha-MSH1-13), a peptide derived from proopiomelanocortin, has remarkable anti-inflammatory and antipyretic activities. This peptide and a tripeptide that forms the COOH-terminal portion of the molecule (alpha-MSH11-13; Lys Pro Val) inhibit inflammation when given centrally or peripherally. Because of the similarity in their actions, the tripeptide has been presumed to be the amino acid message sequence underlying the effects of alpha-MSH1-13. To test the possibility that the two peptides occupy the same receptors, competitive binding experiments were performed with B16 mouse melanoma cells that are known to have alpha-MSH1-13 receptors. In these experiments, alpha-MSH11-13 did not inhibit binding of a radiolabelled alpha-MSH1-13 analog. This finding suggests that alpha-MSH1-13 and alpha-MSH11-13 exert their anti-inflammatory/antipyretic/anticytokine effects via stimulation of separate receptors. Because alpha-MSH inhibits the effects of several cytokines including inflammation caused by interleukin (IL)-6 and IL-8, the capacity of these cytokines to compete for alpha-MSH binding sites was tested. There was no evidence that these proinflammatory cytokines bind to alpha-MSH receptors on murine melanoma cells. Although further tests with host cells involved in inflammation are required, the latter result is the first evidence that the mechanism of anticytokine action of alpha-MSH does not depend upon peptide/cytokine competition for binding sites.


[Usefulness of antibodies against A60 mycobacterial antigen in tuberculosis diagnosis].
Diagnosis of tuberculosis is based on clinico-radiological symptoms and on identification of mycobacteria. Accuracy of both methods is limited. Therefore reliable serologic test would have considerable advantage. The goal of our study was to evaluate serologic response against A60 mycobacterial antigen in group of 270 patients (pts) (137 pts with active tuberculosis (TB), 15 pts with mycobacterial infections other than TB (MOTT), 58 pts with sarcoidosis, 26 pts with lung cancer and 34 healthy controls. We used commercially available ELISA based kits against antigen A60 (ANDA-TB). Specificity of 87% for IgG, of 94% for IgA and for IgM, of 85% for IgG + IgA, of 89% for IgA + IgM, of 80% for IgG + IgM, and of 79% for IgG + IgA + IgM was achieved. Sensitivity of 40% for IgG, of 30% for IgA, of 18% for IgM, of 56% for IgG + IgA, of 35% for IgM + IgA, of 50% for IgG + IgM, and of 59% for IgG + IgA + IgM was obtained. The results demonstrated that humoral response differs depends on the immunoglobulin class. Measurements of IgG or IgG and IgA as most sensitive against A60 are potentially more useful serological tests in clinical practice. It is not recommended to use tests based on antigen A60 for differentiation tuberculosis and MOTT.


Effect of endothelin-1 on bovine luteal cell function: role in prostaglandin F2alpha-induced antisteroidogenic action.
Endothelin-1 (ET-1) a vasoactive peptide, is synthesized and secreted by endothelial cells. In the bovine corpus luteum (CL), endothelial cells constitute a major proportion (53.5%) of total CL cells. This study was designed to examine the effects of ET-1 on bovine luteal cell functions and its involvement in the action of PGF2alpha. To better define the cells implicated in this process, we used CL slices, whole CL-derived cells, and steroidogenic large (LLC) and small (SLC) luteal-like cells. High affinity binding sites for ET-1 (K(d), approximately 0.3 x 10(-9)) were present in both steroidogenic luteal cells. The binding affinity of ET-1 was 3 orders of magnitude higher than that of ET-3, and a selective ETA receptor antagonist (BQ123) competed similarly to ET-1, suggesting the presence of ETA receptors. The lack of effect of ET-3 on CL-derived cells further supported this conclusion. Both basal progesterone secretion and bovine LH (5 ng/ml)-stimulated progesterone secretion from CL-derived cells were significantly inhibited by ET-1 in a dose-dependent manner, whereas preincubation of these cells with ETA receptor antagonist prevented the inhibitory effect of added ET-1. Incubation of LLC with 10(-8) M ET-1 inhibited their progesterone secretion (114.8 vs. 176.7 ng/10(5) cells-20 h; P < 0.05). On the other hand, ET-1 did not affect progesterone production from SLC despite the presence of ET-binding sites. PGF2alpha only inhibited LH-stimulated progesterone secretion by luteal slices. This antisteroidogenic effect of PGF2alpha could be prevented by the addition of a selective ETA receptor antagonist. Luteal tissue and microvascular endothelial cells isolated from bovine CL produced ET-1; in contrast, the peptide was undetectable in the culture medium or in cell extracts of either LLC or SLC. These data support the concept that ET-1 may play a paracrine regulatory role in bovine luteal function and propose a novel role for this peptide in mediating PGF2alpha-induced luteal regression.


Noncoding RNA Regulation of Dopamine Signaling in Diseases of the Central Nervous System.
Dopaminergic neurotransmission mediates a majority of the vital central nervous system functions. Disruption of these synaptic events provokes a multitude of neurological pathologies, including Parkinson's, schizophrenia, depression, and addiction. Growing evidence supports a key role for noncoding RNA (ncRNA) regulation in the synapse. This review will discuss the role of both short and long ncRNAs in dopamine signaling, including bioinformatic examination of the pathways they target. Specifically, we focus on the contribution of ncRNAs to dopaminergic dysfunction in neurodegenerative as well as psychiatric disease.


Partial HIF-1alpha deficiency impairs pulmonary arterial myocyte electrophysiological responses to hypoxia.
Chronic hypoxia depolarizes and reduces K+ current in pulmonary arterial smooth muscle cells (PASMCs). Our laboratory previously demonstrated that hypoxia-inducible factor-1 (HIF-1) contributed to the development of hypoxic pulmonary hypertension. In this study, electrophysiological parameters were measured in PASMCs isolated from intrapulmonary arteries of mice with one null allele at the Hif1a locus encoding HIF-1alpha [Hif1a(+/-)] and from their wild-type [Hif1a(+/+)] littermates after 3 wk in air or 10% O2. Hematocrit and right ventricular wall and left ventricle plus septum weights were measured. Capacitance, K+ current, and membrane potential were measured with whole cell patch clamp. Similar to our laboratory's previous results, hypoxia-induced right ventricular hypertrophy and polycythemia were blunted in Hif1a(+/-) mice. Hypoxia increased PASMC capacitance in Hif1a(+/+) mice but not in Hif1a(+/-) mice. Chronic hypoxia depolarized and reduced K+ current density in PASMCs from Hif1a(+/+) mice. In PASMCs from hypoxic Hif1a(+/-) mice, no reduction in K+ current density was observed, and depolarization was significantly blunted. Thus partial deficiency of HIF-1alpha is sufficient to impair hypoxia-induced depolarization, reduction of K+ current density, and PASMC hypertrophy.


[Removing breast foreign body resulted from augmentation with polyacrylamide hydrogel injection and silicone prosthesis implantation at one stage].
This study was to investigate an operation, in which removing breast cysts of foreign body resulted from augmentation with polyacrylamide hydrogel injection was performed simultaneously with silicone prosthesis implantation under SEPS endoscope in order to relieve tissue injury and increase the accuracy of clearance. Eight patients were included in this study. Preoperative type B ultrasound examination was performed to mark the mass. Through an axillary approach, the cysts of foreign body that were distributed in the subcutaneous tissue, breast or muscle were separated and ablated under SEPS endoscope. After removal of the foreign body, a silicone implant was located submuscularly for breast augmentation. The operations were completed without hematoma and infection. Follow-up of the eight patients for 3 to 12 months showed that preoperative symptoms relating to the injected material, such as breast pain, lump and asymmetry, have no longer existed. The shapes of the breasts were satisfactory. We believe that endoscope-assisted mammoplasty offers more satisfactory clinical results with less injury, less morbidity, less scars, more accuracy and greater patient acceptance.


Transient ischemic attack incidence in joinville, Brazil, 2010: a population-based study.
There are scarce data on transient ischemic attack incidence in low- and middle-income countries. We aimed to measure transient ischemic attack incidence and the distribution of the ABCD2 risk score in Joinville, Brazil. In 2009 to 2010, using a multiple overlapping sources, we ascertained all first ever probable and definite transient ischemic attacks. We recorded 74 definite and probable transient ischemic attacks. The crude incidence was 15 (12-18) per 100 000 population. Age adjusted to European population the incidence was 28 (22-35). One fourth was in the higher risk of stroke by the ABCD2 scale. The transient ischemic attack incidence in Joinville, Brazil, is lower than other well-designed studies. New studies could clarify whether the measured rates were due to underascertainment or reflect a truly low incidence.


Role of local authority homes in the care of the dependent elderly: a prospective study.
A two-year prospective study of 11 local authority homes showed no increase in the degrees of behavioural disabilities or the prevalence of dependency or dementia among the residents. This finding, which differed from trends reported in other studies, was unlikely to be due to the design of the study and occurred in the absence of a co-ordinated service for the elderly. It was probably the effect of changes in the admission policy of the social-work services and suggests that, in some parts of Britain at least, residential homes are no longer absorbing additional numbers of dependent or demented old people in need of institutional care.


Seizure outcome with surgical management of epileptogenic ganglioglioma: a study of 55 patients.
Ganglioglioma is a common seizure-associated tumor, and some factors that may influence the postoperative seizure outcome have not been discussed or are controversial. The goal of this study was to observe the postoperative seizure outcome and the prognostic factors in patients with epileptogenic gangliogliomas. In this retrospective study, 55 patients with epileptogenic gangliogliomas underwent surgery. Postoperative seizure outcome during follow-up was recorded, and possible postoperative prognostic factors were analyzed. There were 30 males and 25 females in our study. Twenty patients presented with chronic seizures. The mean age at surgery was 19.39 years, and the mean seizure duration prior to surgery was 4.47 years. Forty-three patients had complex partial seizures, 12 patients had simple partial seizures, and secondary generalization occurred in 18 patients. Brain magnetic resonance imaging (MRI) revealed 32 tumors were located in the temporal lobe and 23 in the extratemporal lobes. Intraoperative electrocorticography (ECoG) and intraoperative ultrasound (IOUS) were used in 42 and 11 patients, respectively. Gross total resection of the tumor was achieved in 42 patients (1 patient underwent reoperation), subtotal resection in 11, and partial resection in 2. Simple lesionectomy and tailored epilepsy surgery were performed in 24 and 31 patients, respectively. After a mean follow-up of 3.27 years, 48 patients, including 1 re-operated patient, were seizure free (Engel class I). None of the factors, including age at surgery, seizure duration prior to surgery, the type of seizures, use of intraoperative ECoG and IOUS, extent of tumor resection, and surgical strategy, proved to be significantly correlated with postoperative seizure outcome. Surgical treatment is effective and safe for patients with epileptogenic gangliogliomas. Early surgical intervention is necessary for achieving early seizure control. Neither intraoperative ECoG nor IOUS necessarily leads to better seizure control, although the latter can be helpful in achieving complete tumor resection. Simple lesionectomy is sufficient for favorable postoperative seizure outcome.


Bixin Prevents Colorectal Cancer Development through AMPK-Activated Endoplasmic Reticulum Stress.
Chemicals isolated from natural products have been broadly applied in the treatment of colorectal cancer (CRC). Bixin, an apocarotenoid from the seeds of Bixa orellana, exerts multiple pharmacological properties, including neuroprotective, anti-inflammatory, cardioprotective, and antitumor effects; yet, the therapeutic effects of Bixin on CRC are still unknown. Here, we described that Bixin treatment significantly inhibited the proliferation and motility of two CRC cell lines (CaCO2 and SW480) in vitro and in vivo. In addition, Bixin administration has sensitized CRC cells to TNF-related apoptosis-inducing ligand- (TRAIL-) induced cell apoptosis. Moreover, we showed that Bixin treatment initiated the activation of PERK/eIF-2α signal in CaCO2 and SW480 cells, leading to endoplasmic reticulum stress-associated apoptosis. Pharmacological inhibition of AMP-activated protein kinase (AMPK) abrogated the Bixin-induced activation of protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2 alpha (eIF-2α) pathway, as well as reversed the inhibitory effects of Bixin on CRC development. In conclusion, this study indicated that Bixin treatment inhibits the progression of CRC through activating the AMPK/PERK/eIF-2α pathway, providing a novel potential strategy for clinical prevention of CRC.


Comparative phosphoproteomics reveal new candidates in the regulation of spermatogenesis of Drosophila melanogaster.
The most common phenotype induced by the endosymbiont Wolbachia in insects is cytoplasmic incompatibility, where none or fewer progenies can be produced when Wolbachia-infected males mate with uninfected females. This suggests that some modifications are induced in host sperms during spermatogenesis by Wolbachia. To identify the proteins whose phosphorylation states play essential roles in male reproduction in Drosophila melanogaster, we applied isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic strategy combined with titanium dioxide (TiO2 ) enrichment to compare the phosphoproteome of Wolbachia-infected with that of uninfected male reproductive systems in D. melanogaster. We identified 182 phosphopeptides, defining 140 phosphoproteins, that have at least a 1.2 fold change in abundance with a P-value of <0.05. Most of the differentially abundant phosphoproteins (DAPPs) were associated with microtubule cytoskeleton organization and spermatid differentiation. The DAPPs included proteins already known to be associated with spermatogenesis, as well as many not previously studied during this process. Six genes coding for DAPPs were knocked down, respectively, in Wolbachia-free fly testes. Among them, Slmap knockdown caused the most severe damage in spermatogenesis, with no mature sperm observed in seminal vesicles. Immunofluorescence staining showed that the formation of individualization complex composed of actin cones was completely disrupted. These results suggest that Wolbachia may induce wide changes in the abundance of phosphorylated proteins which are closely related to male reproduction. By identifying phospho-modulated proteins we also provide a significant candidate set for future studies on their roles in spermatogenesis.


Syntheses, structural characterization and CO releasing properties of boranocarbonate [H3BCO2H]- derivatives.
CO plays an important role in biological processes and molecules which release CO in a controllable way could therefore be used for medicinal purposes. Beside organometallic carbonyl complexes, boranocarbonate [H(3)BCO(2)H](-) is one of the most promising candidates but releases CO too rapidly. In order to delay the CO release, we have prepared boranocarbamates [H(3)BCONH-R](-) from [H(3)BCO(2)H](-) which comprise histamine, morpholine, aniline and ethylene-diamine bound via amides to the {H(3)BCO} moiety. The syntheses of the new derivatives is described together with their structural characterization. These compounds release CO at a much slower rate than the parent compound and are therefore potential CO releasing molecules for biological and medicinal application.


Hyperamylasemia and pancreatitis in leptospirosis.
Hyperamylasemia has been documented in up to 65% of our patients with leptospirosis and jaundice. However, pancreatitis is an uncommon complication of leptospirosis. Three patients with leptospirosis and pancreatitis are described and compared with two leptospirosis patients who had hyperamylasemia but in whom the diagnosis of pancreatitis could not be substantiated. The cause of the hyperamylasemia in the latter patients was nonpancreatic. The elevation of the amylase in these latter two patients could not be explained by renal insufficiency, because the level of the amylase was greater than three to four times the normal value, the upper limit to which amylase rises in renal failure. Thus, hyperamylasemia in patients with leptospirosis can be from pancreatic and nonpancreatic sources. Leptospirosis should be considered in the differential diagnosis of hyperamylasemia and pancreatitis.


Sympathetic skin response in patients with primary premature ejaculation.
To evaluate the possible role of the autonomic (sympathetic) nervous system function among the patients with primary premature ejaculation (PPE) and determine whether there is an etiological basis for this condition. We performed sympathetic skin response located in the penis (PSSR) in 52 patients with PPE and 46 normally potent men. The latencies and amplitudes of PSSR were measured. The PSSR waveforms were classified into P type and N type according to the waveform characteristics. The waveform distribution in the PPE patients was not statistically different from that in the control group (P=0.609). Mean latency of the PSSR was significantly shorter in the patients than that in the normally potent men (P<0.001). Mean amplitude of the PSSR was significantly greater in patients than that in the normal men (P<0.001). Patients with PPE have hyperactivity of the sympathetic nervous system, which may be another factor involved in the pathological mechanisms of PPE, and the PSSR is an objective test to evaluate patients with PPE.


Characterization of a neurotoxigenic Clostridium butyricum strain isolated from the food implicated in an outbreak of food-borne type E botulism.
Neurotoxigenic Clostridium butyricum was isolated from the food implicated in an outbreak of clinically diagnosed type E botulism in China. PCR assay showed that the isolate (LCL 155) contained the type E botulinum toxin gene. This appears to be the first report of neurotoxigenic C. butyricum causing food-borne botulism.


Cerebrospinal fluid shunt survival and etiology of failures: a seven-year institutional experience.
Innovations in shunt technology and neuroendoscopy have been increasingly applied to shunt management. However, the relative life span of shunts and the etiology of shunt failure have not been characterized recently. We reviewed the records of all shunting procedures at our institution between January 1992 and December 1998. Independent predictors of shunt failure were analyzed via multivariate Cox regression analysis in 836 shunting procedures. Independent predictors of the etiology of failure (infection, proximal obstruction, distal malfunction) were analyzed via multivariate logistic regression analysis in the 383 shunts which failed. A total of 353 pediatric patients underwent 308 shunt placements and 528 revisions. The risk (hazard ratio; HR) of shunt failure decreased as a function of time in both primary placements and revised shunts. In failed shunts, the odds of infection decreased 4-fold per year of shunt function, while the odds of distal malfunction increased 1.45-fold per year. Increasing number of shunt revisions (HR 1.31, p < 0.05), decreasing patient age in years (HR 1.04, p < 0.001), gestational age <40 weeks (HR 2.15, p < 0.001) but not the etiology of hydrocephalus were associated with an increased risk of shunt failure. Revisions versus primary placements, Dandy-Walker cysts and gestational age <40 weeks were independently associated with proximal, distal and infectious causes of failure, respectively. The long-term shunt revision rates observed here are similar to those reported over the past 2 decades. Shunt life span remains poorer in shunt revisions and in younger patients. Patient characteristics may suggest a specific risk and mechanism of failure, aiding in the long-term management of shunted hydrocephalus.


Transesophageal echocardiographic evaluation for mural thrombus following radiofrequency catheter ablation of accessory pathways.
Catheter ablation of accessory pathways (APs) provides a definitive therapy for patients with Wolff-Parkinson-White Syndrome. The reported incidence of thrombus formation on ablation-induced injuries with direct current shock varies from 0%-20% in animal studies. The purpose of this study was to determine the prevalence of mural thrombus following catheter ablation with radiofrequency current of accessory pathways in humans. Radiofrequency current (30-35 watts) was applied through a catheter electrode placed against the mitral or tricuspid annulus guided by catheter recordings of AP potentials. Transthoracic (TTE) and transesophageal echocardiography (TEE) were performed in 95 of 111 patients, at 18 +/- 6 hours following catheter ablation. After ablation, no thrombus was identified at or near the ablation site in any patient. Two out of 95 patients had a mural thrombus at a remote site that was detected by TEE but not by TTE. No new wall motion abnormality was detected in any patient. No significant regurgitant valvular lesion was found in any patient. Intracardiac thrombus was not identified at the site of catheter ablation, possibly owing to the small lesions produced by radiofrequency energy and high blood flow normally present in those areas. However, patients may be at small risk for mural thrombus at a remote site from prolonged placement of catheters.


Monoclonal antibodies to purified muscarinic receptor display agonist-like activity.
Monoclonal antibody M-35, which immunoprecipitates native calf brain acetylcholine muscarinic receptor, mimics agonist stimulation of the intact guinea pig myometrium: the antibody, just like carbamoylcholine hydrochloride, causes a rise in intracellular cyclic GMP content, an inhibition of cyclic AMP accumulation due to prostacyclin, and induces uterine contractions. Another antibody, M-23, which reacts with the denatured muscarinic receptor, is devoid of agonist-like activity at the cyclic nucleotide level but is still able to induce contractions of both rat and guinea pig myometrium. The cyclic nucleotide changes caused by both carbamoylcholine and antibody M-35 are inhibited by atropine; this antagonist, which blocks carbamoylcholine-mediated contractions, fails however, to prevent contractions induced by antibodies M-35 and M-23. These results suggest that the information necessary to transmit muscarinic signals is entirely contained in the receptor and that ligands only act to trigger the biological response. The data also imply that the muscarinic receptors of the myometrium are coupled to multiple effector systems.


Prion amyloid structure explains templating: how proteins can be genes.
The yeast and fungal prions determine heritable and infectious traits, and are thus genes composed of protein. Most prions are inactive forms of a normal protein as it forms a self-propagating filamentous β-sheet-rich polymer structure called amyloid. Remarkably, a single prion protein sequence can form two or more faithfully inherited prion variants, in effect alleles of these genes. What protein structure explains this protein-based inheritance? Using solid-state nuclear magnetic resonance, we showed that the infectious amyloids of the prion domains of Ure2p, Sup35p and Rnq1p have an in-register parallel architecture. This structure explains how the amyloid filament ends can template the structure of a new protein as it joins the filament. The yeast prions [PSI(+)] and [URE3] are not found in wild strains, indicating that they are a disadvantage to the cell. Moreover, the prion domains of Ure2p and Sup35p have functions unrelated to prion formation, indicating that these domains are not present for the purpose of forming prions. Indeed, prion-forming ability is not conserved, even within Saccharomyces cerevisiae, suggesting that the rare formation of prions is a disease. The prion domain sequences generally vary more rapidly in evolution than does the remainder of the molecule, producing a barrier to prion transmission, perhaps selected in evolution by this protection.


[The effect of the dependency burden on household savings in parts of central Sumatra].
The demographic impact of family size on household savings is examined. Saving is defined as "the difference between income and expenditure. Household size and number of children at school are used as the independent variables.... The paper concludes that household size negatively affects household saving." Data are from the 1987 Indonesian census. (SUMMARY IN ENG)


Efficacy of Extended Modification in Left Hemihepatectomy for Advanced Perihilar Cholangiocarcinoma: Comparison Between H12345'8'-B-MHV and H1234-B.
The aim of this study was to verify the prognostic impact of the tumor exposure at the liver transection margin (LTM) in left-sided perihilar cholangiocarcinoma and the impact of middle hepatic vein (MHV) resection on this exposure. In perihilar cholangiocarcinoma, tumors are unexpectedly exposed at the LTM during left hemihepatectomy (LH). Patients who underwent LH for perihilar cholangiocarcinoma during 2002 to 2018 were retrospectively evaluated. LH was classified into conventional and extended types, which preserved and resected the MHVs, respectively. Positive LTM was defined as the involvement of invasive carcinoma at the liver transection plane and/or the adjacent Glissonean pedicle exposed. The clinicopathologic features and survival outcomes were compared between procedures. Among 236 patients, conventional and extended LHs were performed in 198 and 38 patients, respectively. The LTM was positive in 31 (13%) patients, with an incidence of 14% versus 8% ( P = 0.432) and 24% versus 0% in advanced tumors ( P = 0.011). Tumor size ≥ 18 mm ( P = 0.041), portal vein invasion ( P = 0.009), and conventional LH ( P = 0.028) independently predicted positive LTM. In patients with negative LTM, the survival was comparable between the two groups: 60.4% versus 59.2% at 3 years ( P = 0.206), which surpassed 17.7% for those with positive LTM in the conventional group ( P < 0.001). Multivariable analysis demonstrated that LTM status was an independent prognostic factor ( P = 0.009) along with ductal margin status ( P = 0.030). The LTM status is an important prognostic factor in perihilar cholangiocarcinoma. Extended LH reduced the risk of tumor exposure at the LTM with a subsequent improvement in the survival, particularly in advanced tumors.


Concentration changes of methanol in blood samples during an experimentally induced alcohol hangover state.
A hangover is characterized by the unpleasant physical and mental symptoms that occur between 8 and 16 hours after drinking alcohol. After inducing experimental hangover in normal individuals, we measured the methanol concentration prior to and after alcohol consumption and we assessed the association between the hangover condition and the blood methanol level. A total of 18 normal adult males participated in this study. They did not have any previous histories of psychiatric or medical disorders. The blood ethanol concentration prior to the alcohol intake (2.26+/-2.08) was not significantly different from that 13 hours after the alcohol consumption (3.12+/-2.38). However, the difference of methanol concentration between the day of experiment (prior to the alcohol intake) and the next day (13 hours after the alcohol intake) was significant (2.62+/-1.33/l vs. 3.88+/-2.10/l, respectively). A significant positive correlation was observed between the changes of blood methanol concentration and hangover subjective scale score increment when covarying for the changes of blood ethanol level (r=0.498, p<0.05). This result suggests the possible correlation of methanol as well as its toxic metabolite to hangover.


A Novel Subtype of Bovine Hepacivirus Identified in Ticks Reveals the Genetic Diversity and Evolution of Bovine Hepacivirus.
Hepaciviruses represent a group of viruses that pose a significant threat to the health of humans and animals. New members of the genus Hepacivirus in the family Flaviviridae have recently been identified in a wide variety of host species worldwide. Similar to the Hepatitis C virus (HCV), bovine hepacivirus (BovHepV) is hepatotropic and causes acute or persistent infections in cattle. BovHepVs are distributed worldwide and classified into two genotypes with seven subtypes in genotype 1. In this study, three BovHepV strains were identified in the samples of ticks sucking blood on cattle in the Guangdong province of China, through unbiased high-throughput sequencing. Genetic analysis revealed the polyprotein-coding gene of these viral sequences herein shared 67.7-84.8% nt identity and 76.1-95.6% aa identity with other BovHepVs identified worldwide. As per the demarcation criteria adopted for the genotyping and subtyping of HCV, these three BovHepV strains belonged to a novel subtype within the genotype 1. Additionally, purifying selection was the dominant evolutionary pressure acting on the genomes of BovHepV, and genetic recombination was not common among BovHepVs. These results expand the knowledge about the genetic diversity and evolution of BovHepV distributed globally, and also indicate genetically divergent BovHepV strains were co-circulating in cattle populations in China.


Bibliometric review of ATAC-Seq and its application in gene expression.
With recent advances in high-throughput next-generation sequencing, it is possible to describe the regulation and expression of genes at multiple levels. An assay for transposase-accessible chromatin using sequencing (ATAC-seq), which uses Tn5 transposase to sequence protein-free binding regions of the genome, can be combined with chromatin immunoprecipitation coupled with deep sequencing (ChIP-seq) and ribonucleic acid sequencing (RNA-seq) to provide a detailed description of gene expression. Here, we reviewed the literature on ATAC-seq and described the characteristics of ATAC-seq publications. We then briefly introduced the principles of RNA-seq, ChIP-seq and ATAC-seq, focusing on the main features of the techniques. We built a phylogenetic tree from species that had been previously studied by using ATAC-seq. Studies of Mus musculus and Homo sapiens account for approximately 90% of the total ATAC-seq data, while other species are still in the process of accumulating data. We summarized the findings from human diseases and other species, illustrating the cutting-edge discoveries and the role of multi-omics data analysis in current research. Moreover, we collected and compared ATAC-seq analysis pipelines, which allowed biological researchers who lack programming skills to better analyze and explore ATAC-seq data. Through this review, it is clear that multi-omics analysis and single-cell sequencing technology will become the mainstream approach in future research.


Long-term follow-up of the first breast conservation trial: Guy' wide excision study.
Breast conservation therapy is now accepted as a proven approach for selected patients with operable breast cancer. Nevertheless, it is important to appreciate that the first randomized trials, which were carried out at Guy's Hospital, indicated the need for good local control and the increased mortality from breast cancer which occurred when treatment was sub-optimal. In the first trial 374 women aged > or = 50, with T1, T2, N0 and N1 tumours were randomized to either Halsted mastectomy and postoperative radiotherapy or wide excision and postoperative irradiation. Both groups were given 25-27 Gy to the gland fields and the wide excision group received additionally 35-38 Gy to the breast. Hence the wide excision group had no axillary surgery and subsequent axillary irradiation using what is now regarded as a low dose of radiotherapy. After 25 years, local relapse has occurred in 26% of the mastectomy group and 50% of the wide excision group (chi(2)= 21.6, P < 0.001). The breast cancer mortality rate at 25 years was 56% in the mastectomy group and 63% in those treated by wide excision (chi(2)= 5.33, P= 0.02). The first analysis of this trial indicated that increased risk of axillary relapse was restricted to N1 cases and so a second trial was conducted with entry only for those with clinically negative axillae (N0 series). Of 255 cases entered, 133 were randomized to mastectomy and 122 to wide excision. The same radiotherapy schedule was used as in the original Series. After 25 years local relapse occurred in 18% of the mastectomy cases and 54% of the wide excision group (chi(2)= 30.6, P < 0.001). There were significantly more distant relapse in the latter group (chi(2)= 6.32, P= 0.01), and a significant increase in breast cancer deaths (57% versus 44%, chi(2)= 4.27, P= 0.04). These two trials, conducted before the widespread introduction of systemic adjuvant therapy, both indicate the long-term effects of inadequate primary treatment. Inadvertent failure to treat the axilla effectively led not only to significantly increased axillary relapse rates but also to more deaths from metastatic disease.


The effects of digitonin on photochemical activities of isolated chloroplasts.
The addition of digitonin to chloroplasts stimulated the rate of oxygen evolution followed by a gradual inhibition. The effect of digitonin was dependent on the digitonin to chlorophyll ratio and on temperature and time. The initial stimulation of oxygen evolution appeared to be a result of uncoupling as digitonin did not stimulate oxygen evolution by uncoupled chloroplasts. The stimulatory effect occurred more rapidly at high digitonin to chlorophyll ratios but the extent of stimulation was low and inhibition occurred soon after addition of the detergent. The inhibition of electron flow by digitonin was due to a site of action near photosystem II which resembled the inhibition reported for tris buffer and resulted in photobleaching. However, digitonin inhibition could not be recovered by washing with reducing agents and was only partially recovered by the addition of artificial electron donors to photosystem II. Electron flow mediated by photosystem I was unaffected by the addition of digitonin but was decreased when the chloroplasts were separated by subsequent centrifuging. This suggested that digitonin solubilizes photosystem I components which remain active in the soluble form.


High-avidity human serum antibodies recognizing linear epitopes of Borna disease virus proteins.
The recent observation that Borna disease virus (BDV)-reactive antibodies from psychiatric patients exhibit only low avidity for BDV antigen called into question their diagnostic value and raised the possibility that antigenically related microorganisms or self antigens caused the production of these antibodies. We further characterized the specificity of these antibodies. We established a peptide array-based screening test that allows the identification of antibodies directed against linear epitopes of the two major BDV proteins, the nucleoprotein (N) and the phosphoprotein (P). Initial tests employing sera of BDV-infected mice and rats or horses with Borna disease revealed a high specificity and sensitivity of this test. All sera recognized epitopes of N, P, or both. Sera of noninfected rats, mice, and horses showed no signals on either peptide array. Several human sera that recognized BDV antigen by indirect immunofluorescence contained antibodies that recognized various linear epitopes of one or even both BDV proteins. Remarkably, antibodies purified from such human serum by matrix-immobilized peptides showed high-avidity binding to BDV antigens when assayed by IFA or Western blotting. These data suggest that reactive antibodies found in psychiatric patients indeed indicate infection with BDV or a BDV-like agent. However, the poor affinity maturation of BDV-specific human antibodies remains unexplained.


Antigen challenge and canine tracheal mucus.
Tracheal mucus hypersecretion was demonstrated in 7 dogs with cutaneous sensitivity to extracts of Ascaris suum when the dogs were exposed to aerosols of the same antigen. There was a correlation between antigen skin sensitivity and the aerosol dose at which hypersecretion first occurred. In addition to hypersecretion, antigen challenge led to significant alterations in mucus viscoelasticity. The dose-response pattern was similar to that seen with methacholine and histamine aerosol administration in dogs employing the same methodology. The antigen-induced hypersecretion was blocked or substantially reduced by pretreatment with atropine, H1-antagonists, and thiazinamium chloride. These observations suggest that mucus hypersecretion associated with A. suum challenge in dogs involves histamine release and proceeds at least in part via a cholinergic mechanism.


Effect of dietary intake on pattern of growth of dominant follicles during the oestrous cycle in beef heifers.
Friesian x Hereford heifers (n = 19; mean +/- s.e.m. body weight (BW) = 375 +/- 5 kg) were used in a randomized incomplete block design. Heifers were fed 0.7 (n = 7; L), 1.1 (n = 7; M) or 1.8% (n = 5; G) of BW in dry matter (DM)/day for 10 weeks. Ovaries were examined by ultrasound, for one oestrous cycle, from week 5 of treatment. Maximum diameter of dominant follicles was smaller (P less than 0.05) in L (11.8 +/- 0.1 mm) than in M (13.7 +/- 0.2 mm) or G (13.2 +/- 0.3 mm) heifers. Growth rate (mm/day) of dominant follicles during the oestrous cycle was not affected (P greater than 0.05) by dietary intake. Persistence of dominant follicles was shorter (P less than 0.05) in L (9.8 +/- 0.2 days) than in M (11.9 +/- 0.3 days) or G (12.7 +/- 0.4 days) heifers. Three dominant follicles were identified during the oestrous cycle of 5 of 7 L, 3 of 7 M and 1 of 5 G heifers (P less than 0.10); 2 dominant follicles were identified in the remaining heifers (n = 2 of 7, 4 of 7 and 4 of 5, respectively). Length of the luteal phase and luteal-phase concentrations of progesterone were not affected (P greater than 0.05) by treatment. Low dietary intake reduced the diameter and persistence of dominant follicles during the oestrous cycle of beef heifers and tended to increase the proportion of oestrous cycles with 3 dominant follicles.


Antiinflammatory activity of topically applied sertaconazole nitrate.
The antiinflammatory activity of topically applied sertaconazole nitrate was investigated. The dermal administration of 2% sertaconazole to rats, in which edema was induced by application of croton oil in the external ear, induced a 39.8% reduction of edema. The results show that sertaconazole applied by topical route at the concentration at which it is used in clinic, has antiinflammatory action in this experimental model.


The effects of residential locality on parental and alloparental investment among the Aka foragers of the central African Republic.
In this paper I examine the intracultural variability of parental and alloparental caregiving among the Aka foragers of the Central African Republic. It has been suggested that maternal kin offer higher frequencies of allocare than paternal kin and that maternal investment in infants will decrease when alloparental assistance is provided. Behavioral observations were conducted on 15 eight- to twelve-monthold infants. The practice of brideservice and the flexibility of Aka residence patterns offered a means to test the effect of maternal residence on parental and alloparental investment. There was significant variation in the frequency of investment and who supplied care to infants depending on whether mothers resided with their kin or their husbands' kin. However, in spite of the variation in allocare, when all categories of caregivers were examined collectively, infants received similar overall levels of care.


Measurement of plasma metallothionein-I in the assessment of the zinc status of zinc-deficient and stressed rats.
These studies were designed to investigate the effects of stress and of changes in zinc status on plasma and liver concentrations of metallothionein-I (MT-I) in rats and to assess the value of plasma MT-I assays in the diagnosis of zinc deficiency. No MT-I was detected by radioimmunoassay in the plasma or liver of rats made hypozincaemic by feeding diets with less than 1 or 3 mg Zn/kg. Injection of normal rats with endotoxin or CCl4 also decreased plasma zinc levels, but these treatments greatly increased MT-I concentrations in both liver and plasma. Moreover plasma MT-I levels in zinc-deprived rats given endotoxin were only slightly greater than those in untreated rats of normal zinc status. Neither plasma zinc nor MT-I levels were altered in starved rats despite increased levels of the protein in the liver, although a slight increase in plasma MT-I was found in rats pair-fed with zinc-deficient animals. It appears therefore that reduced plasma levels of both zinc and MT-I are indicative of a zinc deficiency state and that assay of plasma MT should be of value in the diagnosis of zinc deficiency.


Pentalene complexes of group 7 metal carbonyls: an organometallic mixed-valence system with very large metal-metal electronic coupling.
The bimetallic complexes [M(CO)(3)](2)(mu:eta(5):eta(5)-Pn) (Pn = pentalene, C(8)H(6); M = Mn, Re) have been synthesized and characterized crystallographically; the Mn compound was isolated as solely the anti-isomer, while the Re analogue was formed as a mixture of anti- and syn-isomers. [Mn(CO)(3)](2)(mu:eta(5):eta(5)-Pn) may be reduced chemically to its mono- and dianions; the mixed-valence Mn(I)/Mn(0) monoanion is shown by ESR, vibrational, and electronic spectroscopies to be a Robin-Day class III system with an exceptionally large electronic coupling between the metal centers.


Facile access to a heterocyclic, sp(3)-rich chemical scaffold via a tandem condensation/intramolecular nitrone-alkene [3+2] cycloaddition strategy.
A heterocyclic, sp(3)-rich chemical scaffold was synthesised in just 6 steps via a highly regio- and diastereo-selective tandem nitrone formation/intramolecular nitrone-alkene [3+2] cycloaddition reaction. A library of 543 lead-like compounds based on the scaffold core has been produced.


Dyslipidemia and the progression of renal disease in chronic renal failure patients.
Dyslipidemia is a common complication of progressive kidney disease and contributes to the high cardiovascular morbidity and mortality of chronic kidney disease (CKD) patients. Recent evidence also suggests a role for dyslipidemia in the development and progression of renal disease. Experimental studies have demonstrated that lipids may induce glomerular and tubulointerstitial injury, and that lipid-lowering treatments ameliorate renal injury. Various lipid abnormalities have been associated with the development and progression of renal disease in diabetic and nondiabetic patients. Population-based studies and studies of diabetic patients have reported associations of various lipid abnormalities with the development of renal disease. In patients with CKD, lipid abnormalities have also been associated with renal disease progression. Post hoc analyses of some large clinical trials on patients with vascular disease, diabetes, or dyslipidemia, and a meta-analysis of small, prospective, controlled studies on patients with CKD (diabetics and nondiabetics) suggest that statins may slow the progression of kidney disease. It is unclear whether the beneficial renal effects of statins are due to the reduction of serum cholesterol levels and/or their pleiotropic effects. There is also evidence for synergistic renoprotective effects between statins and renin-angiotensin system inhibitors. According to the results of post hoc analysis of several studies, treatment with fibrates does not seem to confer renoprotection, but evidence is scarce. In summary, there is growing evidence that lipid abnormalities may be a risk factor for renal disease, and that statins appear to confer a renoprotective effect.


[Sodium-calcium metabolism in myocytes of the small intestine].
It is established that Na+/Ca2+ antiport of small intestine myocytes of plasmatic membranes has the saturation by the transfer substrate. It is characterized by the reversibility and dependence on the membrane potential.


Validation of the DFT/N07D computational model on the magnetic, vibrational and electronic properties of vinyl radical.
The DFT/N07D computational model has been applied to the study of molecular structure, vibrational frequencies and hyperfine coupling constants of vinyl radical in the ground electronic state, taking into account vibrational effects beyond harmonic approximation. Moreover, the TD-DFT/N07D approach has been applied to the study of structures and properties of the title radical in excited electronic states. Vertical and adiabatic electronic excitation energies have been computed and the vibrationally resolved one photon absorption spectrum of the A(2)A''<--X[combining tilde](2)A(1) electronic transition has been simulated. Computational results have been compared with the available experimental data and theoretical studies at the coupled-cluster and MRCI levels, showing remarkable accuracy of the TD-DFT/DFT//N07D model. This finding paves the route toward reliable studies of magnetic, vibrational and electronic properties for quite large unstable open-shell species of current biological and/or technological interest in their ground and excited electronic states.


MANAGEMENT OF ENDOCRINE DISEASE: Regenerative therapies in autoimmune Addison's disease.
The treatment for autoimmune Addison's disease (AAD) has remained virtually unchanged in the last 60 years. Most patients have symptoms that are relatively well controlled with exogenous steroid replacement, but there may be persistent symptoms, recurrent adrenal crisis and poor quality of life, despite good compliance with optimal current treatments. Treatment with conventional exogenous steroid therapy is also associated with premature mortality, increased cardiovascular risk and complications related to excessive steroid replacement. Hence, novel therapeutic approaches have emerged in the last decade attempting to improve the long-term outcome and quality of life of patients with AAD. This review discusses the recent developments in treatment innovations for AAD, including the novel exogenous steroid formulations with the intention of mimicking the physiological biorhythm of cortisol secretion. Our group has also carried out a few studies attempting to restore endogenous glucocorticoid production via immunomodulatory and regenerative medicine approaches. The recent advances in the understanding of adrenocortical stem cell biology, and adrenal plasticity will also be discussed to help comprehend the science behind the therapeutic approaches adopted.


The effect of family-centered education on the quality of life of adolescents with spinal cord injuries.
Spinal injury is a destructive complication creating huge changes in the teen health and lifestyle, depending on its extent and severity. Although most of the complications of this disease are treatable, they impose huge costs on the healthcare system, the patient, and his family. The present study was conducted to investigate the effect of family-centered education on the quality of life and self-esteem of adolescents with spinal cord injuries. The present study is a quasi-experimental study. Adolescents (108 old) with spinal cord injuries entered the present study through stratified sampling with appropriate allocation. The participants were compared in two groups of experimental and control. The data was collected using demographic information questionnaire as well as Ferrans and Powers' quality of life index in spinal cord injury. Four weeks after the intervention, the research questionnaires were completed once more by the adolescents of both groups. Data analysis was conducted by using T-square test, independent t-test, Fisher's exact test, and analysis of variance. According to results, quality of life mean score of adolescents with spinal cord injuries was 23.05 ± 122.65 before the intervention. It became 22.64 ± 148.15 after the intervention. With respect to importance, quality of life mean score of these adolescents changed from 20.83 ± 164.07 to 21.62 ± 174.99. Given the effect of family-centered education on the quality of life in adolescents with spinal cord injuries, it seems essential to create necessary grounds for training families having adolescents with spinal cord injuries by nurses to improve their quality of life as well as conducting researches on their problems.


Localization of CapZ during myofibrillogenesis in cultured chicken muscle.
Actin filaments undergo dramatic changes in their organization during myofibrillogenesis. In mature skeletal muscle, both CapZ and the barbed end of the actin filaments are located at Z-discs. In vitro, CapZ binds the barbed end of actin filaments and prevents actin subunit addition and loss; CapZ also nucleates actin polymerization in vitro. Taken together, these properties suggest that CapZ may function to organize actin filaments during myofibrillogenesis. We report here that the amount of CapZ in myofibrils from adult chicken pectoral muscle is sufficient to "cap" each actin filament of the sacromere. Double immunofluorescence microscopy of skeletal muscle cells in culture was used to determine the spatial and temporal distributions of CapZ relative to actin, alpha-actinin, titin, and myosin during myofibrillogenesis. Of particular interest was the assembly of CapZ at nascent Z-discs in relation to the organization of actin filaments in nascent myofibrils. In myoblasts and young myotubes, CapZ was diffusely distributed in the cytoplasm. As myotubes matured, CapZ was initially observed in a uniform distribution along non-striated actin filaments called stress fiber-like structures (SFLS). CapZ was observed in a periodic pattern characteristic of mature Z-discs along the SFLS prior to the appearance of a striated staining pattern for actin. In older myotubes, when actin was observed in a pattern characteristic of I-bands, CapZ was distributed in a periodic pattern characteristic of mature Z-discs. The finding that CapZ was assembled at nascent Z-discs before actin was observed in a striated pattern is consistent with the hypothesis that CapZ directs the location and polarity of actin filaments during I-band formation in skeletal muscle cells. The assembly of CapZ at nascent Z-disc structures also was observed relative to the assembly of sarcomeric alpha-actinin, titin, and thick filaments. Titin and myosin were observed in structures having the organization of mature sarcomeres prior to the appearance of CapZ at nascent Z-discs. The distribution of CapZ and sarcomeric alpha-actinin in young myotubes was not coincident; in older myotubes, both CapZ and alpha-actinin were co-localized at Z-discs. In cardiac myocytes, CapZ was detected at Z-discs and was distributed in a punctate pattern throughout the cytoplasm. CapZ also was co-localized with A-CAM and vinculin at cell-cell junctions formed by the myocytes.


[Study on the usefulness of rinse containing miconazole nitrate for treatment of dandruff--a double-blind, comparative study].
A double-blind, comparative study was performed on the usefulness of rinse containing miconazole nitrate(COFRM)compared to rinse without the reagent for the treatment of dandruff, when together with shampoo containing miconazole nitrate (COF). This study showed that both COFR and COFRM had about 80% utility. On the other hand, though it was not significant, enhanced improvement of itching by COFRM compared to COFR was detected 2 weeks after start of the examination. These results suggest that by mixing the miconazole nitrate with not only the shampoo but also rinse, the reagent more certainly remained on the scalp so that proliferation of the Malassezia was disturbed. Therefore, the effectiveness could clearly be more practically felt at the early stage. Collectively, these results indicate that COFRM was a useful rinse that allowed the effect to actually be felt in the short-term when used together with COF and contributed to the compliance improvement.


Simple surrogate index of the fibrosis stage in chronic hepatitis C patients using platelet count and serum albumin level.
This study was conducted to develop a simple surrogate index comprised of routinely available laboratory tests to reflect the histological fibrosis stage. Clinical characteristics and laboratory data from 368 and 249 consecutive patients with chronic hepatitis C, a training cohort and a validation cohort, respectively, were retrospectively evaluated. Platelet (Plt) count and albumin (Alb) level contributed to the discrimination of the respective fibrosis stages. We derived the fibrosis index (FI), FI = 8.0-0.01 x Plt (10(3)/microliter) - Alb (g/dl), from a multiple regression model. FI significantly correlated with the histological fibrosis stage in both the initial and validation cohort at rho=0.691 and rho=0.661, respectively (Spearman's rank correlation coefficient, p<0.0001). The sensitivity and positive predictive value of FI at a cutoff value < 2.10 for predicting fibrosis stage F0-1 were 66.8% and 78.8% in the initial cohort and 68.5% and 63.6% in the validation cohort, respectively. Corresponding values of FI at a cutoff value > or = 3.30 for the prediction of F4 were 67.7% and 75.0% in the initial cohort and 70.8% and 81.0% in the validation cohort. The fibrosis index comprised of platelet count and albumin level reflected the histological fibrosis stage in patients with chronic hepatitis C.


A comparison of equal-appearing interval scaling and direct magnitude estimation of nasal voice quality.
Listeners rated the nasality of synthesized vowels using two psychophysical scaling methods (equal-appearing interval scaling and direct magnitude estimation). A curvilinear relationship between equal-appearing interval ratings and direct magnitude estimations of nasality indicated that nasality is a prothetic rather than metathetic dimension. It also was shown that the use of direct magnitude estimation results in nasality ratings that are more consistent and reliable. The results of this experiment are discussed in relation to other studies that have examined the validity and reliability of equal-appearing interval scaling of voice quality. Additionally, there is a discussion of methodological issues for future research and the implications of the findings for clinical and research purposes.


Extremely low frequency magnetic field and the hatching rate of Fasciola hepatica eggs, the fecundity and survival of liver fluke-infected snail, Lymnaea truncatula.
Eggs of Fasciola hepatica were exposed for 10 days to extremely low frequency magnetic field (ELFMF) at the frequency of 50 Hz and density of 2 mT (rms). The results show an accelerated hatching of F. hepatica eggs in relation to control (non-exposed) group. The host snails, Lymnaea truncatula, were divided into three groups; those of groups I and II were infected with the miracidia of F. hepatica hatched from control egg culture, whereas those of group III were infected with miracidia hatched from eggs affected by ELFMF. Thereafter, snails of groups II and III were exposed to ELFMF for 53 days, whereas those of group I were not exposed. At day 14 post infection, a significant decrease was observed in the number of cocoons laid by snails of group III, compared with control. Also, significant mortality in group III snails was observed 42 days post infection. The increased mortality and a lower number of cocoons laid by group III snails have probably resulted from enhanced stimulation of metacercarial parthenogenetic reproduction in consequence of infecting the molluscs with miracidia reared under ELFMF.


Density Depletion and Enhanced Fluctuations in Water near Hydrophobic Solutes: Identifying the Underlying Physics.
We investigate the origin of the density depletion and enhanced density fluctuations that occur in water in the vicinity of an extended hydrophobic solute. We argue that both phenomena are remnants of the critical drying surface phase transition that occurs at liquid-vapor coexistence in the macroscopic planar limit, i.e., as the solute radius R_{s}→∞. Focusing on the density profile ρ(r) and a sensitive spatial measure of fluctuations, the local compressibility profile χ(r), we develop a scaling theory which expresses the extent of the density depletion and enhancement in compressibility in terms of R_{s}, the strength of solute-water attraction ϵ_{s}, and the deviation from liquid-vapor coexistence δμ. Testing the predictions against results of classical density functional theory for a simple solvent and grand canonical Monte Carlo simulations of a popular water model, we find that the theory provides a firm physical basis for understanding how water behaves at a hydrophobe.


The origin of mesoderm in phoronids.
Descriptive studies of phoronid development have concluded that the mesoderm of these animals originates from the endoderm during gastrulation. This interpretation has been tested by labeling one blastomere of 4- through 16-cell embryos and examining the position and germ layers occupied by the labeled clones of cells in the larva. No 2 injections gave rise to identical clones of cells, suggesting that the cleavage program does not generate cells of unique identity and that cell fates are established at later developmental time points. In many cases, a relatively large sector composed of ectodermal cells was labeled. When these labeled cells were adjacent to the mouth or anus of the larva, muscle and mesenchyme cells originated from the labeled clones. Under these circumstances, nerve cells also originated from these labeled sectors. These labeling studies also showed that endodermal cells can give rise to mesodermal and neural cells. These results suggest that nerve and muscle cells are induced to form at ectodermal-endodermal boundaries from both germ layers. These marking experiments also confirmed the observation that nerve cells originate both from the apical organ and the trunk region and show for the first time that the intestine originates by ingression of posterior ectoderm.


Evaluation of 37 AIDS prevention projects: successful approaches and barriers to program effectiveness.
In 1988, the Robert Wood Johnson Foundation awarded grants to 54 AIDS prevention and service projects. This article presents the results from a survey of the 37 projects that contained a substantial prevention effort and embellishes these findings with qualitative data from in-depth site visits to 12 projects. Survey respondents reported conducting a mean of 19 different intervention activities. Small-group discussion, outreach to populations engaged in high-risk behaviors, and training peers and volunteers were the intervention activities rated most effective by project staff. Qualitative analysis identified eight factors facilitating intervention effectiveness. Three site-visited projects were chosen to exemplify the ways in which these facilitating factors contributed to the perceived effectiveness of small-group discussions, outreach, and the training of peer educators. Recommendations to guide the development and delivery of future community-based AIDS prevention projects are presented.


Solving the puzzle of Fe homeostasis by integrating molecular, mathematical, and societal models.
To ensure optimal utilization and bioavailability, iron uptake, transport, subcellular localization, and assimilation are tightly regulated in plants. Herein, we examine recent advances in our understanding of cellular responses to Fe deficiency. We then use intracellular mechanisms of Fe homeostasis to discuss how formalizing cell biology knowledge via a mathematical model can advance discovery even when quantitative data is limited. Using simulation-based inference to identify plausible systems mechanisms that conform to known emergent phenotypes can yield novel, testable hypotheses to guide targeted experiments. However, this approach relies on the accurate encoding of domain-expert knowledge in exploratory mathematical models. We argue that this would be facilitated by fostering more "systems thinking" life scientists and that diversifying your research team may be a practical path to achieve that goal.


Increased intestinal permeability in endotoxic pigs. Mesenteric hypoperfusion as an etiologic factor.
Infusing pigs with lipopolysaccharide (LPS) decreases superior mesenteric artery blood flow (Qsma), suggesting that mesenteric hypoperfusion may be responsible for LPS-induced alterations in gut mucosal permeability. To test this hypothesis, we studied four groups of anesthetized swine. Group 1 animals (N = 6) were infused with LPS (250 micrograms/kg over 1 hour beginning at 60 minutes) and continuously resuscitated with Ringer's lactate (48 mL/kg per hour). In group 2 (N = 5), Qsma was decreased by 50% by means of a mechanical occluder to mimic the LPS-induced alterations in Qsma observed in group I. Group 3 (N = 5) was included to document our ability to detect ischemia/reperfusion-induced alterations in mucosal permeability; in these pigs, Qsma was decreased in steps to zero flow (at 150 to 210 minutes) and then perfusion was restored (at 210 to 270 minutes). Pigs in group 4 (N = 6) served as normal controls; these animals were resuscitated with Ringer's lactate at the same rate as in group 1 but were not infused with LPS. To assess mucosal permeability, we measured plasma-to-lumen clearances for two markers, chromium 51-labeled edetic acid monohydrate (EDTA) and urea. Loading and maintenance infusions of the markers were given intravenously, and a 20-cm isolated segment of small intestine was continuously perfused at 2 mL/min with Ringer's lactate at 37 degrees C. Results were expressed as the ratio of the clearances for the two probes (CEDTA/CUREA). In group 3, CEDTA/CUREA was 999% +/- 355% of baseline at 270 minutes. In group 1, CEDTA/CUREA was 572% +/- 235% of baseline at 270 minutes. In groups 2 and 4, however, CEDTA/CUREA did not change significantly from the baseline value over the duration of the study. These data suggest that increased mucosal permeability after LPS is due to factors other than (or in addition to) mesenteric hypoperfusion.


Monopolar transurethral resection of the big prostate, experience at Prince Hussein Bin Abdullah Urology Center.
To evaluate and review our experience in management of patients with big size prostate using monopolar transurethral resection of the prostate (TURP). Between January 2005 and March 2010, TURP was performed on 198 patients with prostate size between 80 and 120 grams. The patients were subjected to standard urologic pre-operative evaluation and they were given 5 alpha reductase inhibitor for two weeks before surgery. TURP was performed using 27F continuous-flow resectoscope, Otis urethrotomy and suction cystostomy were done, and 500 ml normal saline with 20mg furosomide was given intraoperatively. Catheterization time, hospital stay, peri-operative and late complications were recorded. All patients were seen at 6 weeks and 6 months post surgery in the outpatient clinic. Symptoms and complications were evaluated and histopathological diagnoses were recorded. The mean age was 67 +/- 3.7 years (range 57-80 years). Of these, 102 patients presented with retention and obstructive uropathy, 36 with recurrent haematuria, 12 with urinary bladder stones, 11 with recurrent urinary tract infection and 37 patients with moderate to severe international prostate symptom score (IPSS) and not responding to medical treatment. The mean prostate volume was 88 +/- 8.22 grams (range 80-120 grams) with an average residual urine of 160 ml (range 20-1500 ml). The mean Qmax was 6.8 +/- 1.7 ml/sec (range 2.1-11.7 ml/sec) and the mean IPSS score was 20.2 +/- 6.2 (range 15-30). The average operative time was 72 +/- 6.2 minutes (range 58-92 minutes). The mean drop in haemoglobin was 3.2 +/- 0.6 mg/dl (range 2.1-6.1 mg/dl) and immediate post-operative mean sodium drop was 3 +/- 1.36 mmol/l (range 0.9-13 mmol/l). Blood transfusion was needed in 17 patients (8.6%), two patients developed TURP syndrome (1%), and clot retention occurred in two patients (1%). The average time of hospital stay was 2.3 +/- 0.25 days, catheterization time was 48-72 hours, and re-catheterization was needed in three patients (1.5%). The mean IPSS score six weeks after surgery was 9.9 +/- 1.7 (range 6-21) and the mean Qmax was 18.1 +/- 2.1 ml/sec (range 6-22). Urethral stricture and bladder neck contracture occurred in 12 and 3 patients respectively (6 and 1.5%). Completion TURP was needed in four patients (2%). Standard monopolar TURP with some modification in resection technique in addition to perioperative care will allow the urologist to treat benign prostate hyperplasia with prostate size between 80-120 grams successfully in centers where new laser technology is not available.


A Five-Year Retrospective Analysis of Basal Cell Carcinoma: A Monocentric Study.
Our aim in this study is to define the histopathological subtypes, body site distribution, and incidence rates of single or multiple of BCCs. The study is conducted on patients from a single institution in Istanbul which has a migrant-receiving population reflecting that of the country overall. We retrospectively analyzed data concerning 896 cases of BCC seen between 2014 and 2018. Data about patient demographics (age and sex), tumor diameter,its anatomic localization, histological type, presence of ulceration, lymphovascular/perineural invasion, and single or multiple tumor formations were retrieved from both the hospital's automated system and archived records of the pathology clinic. Our univariate analysis showed that the patients' age, tumor size, and tumor multicentricity were all significantly related to their gender (p=0.011, p=0.001, and p=0.021, respectively). Further, age, male gender, and tumor size were all significantly related to tumor multicentricity (p=0.003, p=0.021, and p=0.001, respectively). BCC was most commonly found in male, and the diameters of the BCC tumors were also larger in male patients. Multiple BCC was more frequently seen in older and male patients, and the tumors had larger diameters in these groups. The nodular type of BCC was the most frequently seen type in all age groups. As our study is the first BCC study that has the greatest number of cases in Turkey and as Istanbul reflects the population of Turkey, it is important for the data of BCC cases in Turkey.


Human and murine dermis contain dendritic cells. Isolation by means of a novel method and phenotypical and functional characterization.
Dendritic cells (DC) comprise a system of cells in lymphoid and nonlymphoid organs that are specialized to present antigens and to initiate primary T cell responses. The Langerhans cell of the epidermis is used as a prototype for studies of DC in the skin. We have characterized a population of DC in human dermis, one of the first examples of these cells in nonlymphoid organs other than epidermis. To identify their distinct functions and phenotype, we relied upon the preparation of enriched populations that emigrate from organ explants of dermis. The dermal cells have the following key features of mature DC: (a) sheet-like processes, or veils, that are constantly moving; (b) very high levels of surface MHC products; (c) absence of markers for macrophages, lymphocytes, and endothelium; (d) substantial expression of adhesion/costimulatory molecules such as CD11/CD18, CD54 (ICAM-1), B7/BB1, CD40; and (e) powerful stimulatory function for resting T cells. Dermal DC are fully comparable to epidermis-derived DC, except for the lack of Birbeck granules, lower levels of CD1a, and higher levels of CD36. DC were also detected in explants of mouse dermis. We conclude that cutaneous DC include both epidermal and dermal components, and suggest that other human nonlymphoid tissues may also serve as sources of typical immunostimulatory DC.


A novel plant calmodulin-binding protein with a kinesin heavy chain motor domain.
Calmodulin, a ubiquitous calcium-binding protein, regulates many diverse cellular functions by modulating the activity of the proteins that interact with it. Here, we report isolation of a cDNA encoding a novel kinesin-like calmodulin-binding protein (KCBP) from Arabidopsis using biotinylated calmodulin as a probe. Calcium-dependent binding of the cDNA-encoded protein to calmodulin is confirmed by 35S-labeled calmodulin. Sequence analysis of a full-length cDNA indicates that it codes for a protein of 1261 amino acids. The predicted amino acid sequence of the KCBP has a domain of about 340 amino acids in the COOH terminus that shows significant sequence similarity with the motor domain of kinesin heavy chains and kinesin-like proteins and contains ATP and microtubule binding sites typical of these proteins. Outside the motor domain, the KCBP has no sequence similarity with any of the known kinesins, but contains a globular domain in the NH2 terminus and a putative coiled-coil region in the middle. By analyzing the calmodulin binding activity of truncated proteins expressed in Escherichia coli, the calmodulin binding region is mapped to a stretch of about 50 amino acid residues in the COOH terminus region of the protein. Using a synthetic peptide, the calmodulin binding domain is further narrowed down to a 23-amino acid stretch. The synthetic peptide binds to calmodulin with high affinity in a calcium-dependent manner as judged by electrophoretic mobility shift assay of calmodulin-peptide complex. The KCBP is coded by a single gene and is highly expressed in developing flowers and suspension cultured cells. Although many kinesin heavy chains and kinesin-like proteins have been extensively characterized at the biochemical and molecular level in evolutionarily distant organisms, none of them is known to bind calmodulin. The plant kinesin-like protein with a calmodulin binding domain and a unique amino-terminal region is a new member of the kinesin superfamily. The presence of a calmodulin-binding motif in a kinesin heavy chain-like protein suggests a role for calcium and calmodulin in kinesin-driven motor function(s) in plants.


Healthcare management-training and education in the genomic era.
Increasingly the rapid developments by scientists working in the new business sector of biotechnology are being thrust into mainstream news reports. The incredible pace of the creation of neo-knowledge recently leads us to believe there has not been enough time between events for the healthcare sector, the general public, the legislators or the ethicists to reflect and conduct the checks and balances required for thoughtful progress. The decline of the hospital and the emergence of the laboratory as a consequence of the advent of the genomic era signal a profound shift, which will have unprecedented impacts on professionals in the healthcare system and its repercussions will force explicit changes in their education.


In ovo feeding of carbohydrates for broilers-a systematic review.
The purpose of this systematic review was to evaluate the evidence that the injection of carbohydrate-based solutions into embryonated eggs improves broiler performance. A literature search was conducted in April 2017 using the keywords broiler, carbohydrate, in ovo, nutrition and poultry. Only papers that involved in ovo carbohydrate injections in poultry were used in this study. After specific selection criteria, 17 papers were selected. The quality scoring system of the selected studies was based on the injection methodology, use of control groups, type of solution injected, period of injection, egg and hens characteristics, number of variables analysed and the statistical design. Among papers, there was no standardised procedure in to inoculate the solutions. Nevertheless, in general, in ovo feeding of carbohydrates decreases the hatch rate, improves the hatch weight, but it does not seem to influence the post-hatch performance of broilers. The inoculation of 75 mg of glucose in the albumen seems to bring better results. Further studies are needed to improve the technical methodology of in ovo injections for commercial use.


Lung Microbiome in Cystic Fibrosis.
The defective mucociliary clearance due to CFTR malfunctioning causes predisposition to the colonization of pathogens responsible for the recurrent inflammation and rapid deterioration of lung function in patients with cystic fibrosis (CF). This has also a profound effect on the lung microbiome composition, causing a progressive reduction in its diversity, which has become a common characteristic of patients affected by CF. Although we know that the lung microbiome plays an essential role in maintaining lung physiology, our comprehension of how the microbial components interact with each other and the lung, as well as how these interactions change during the disease's course, is still at an early stage. Many challenges exist and many questions still to be answered, but there is no doubt that manipulation of the lung microbiome could help to develop better therapies for people affected by CF.


[The use of tactivin for treating patients with IHD].
Immunomodulating drug tactivin was used for treatment of 29 IHD patients with low T-suppressor activity and high cell sensitization to apoprotein B-containing lipoproteins and with lipoprotein-antibody immune complex detected in the blood. Tactivin was injected subcutaneously in the dose 10 micrograms (5 injections for 12 days). Tactivin treatment normalized T-suppressor activity, lowered concentration of plasma lipoprotein-antibody immune complex and improved clinical course of IHD. The beneficial effect of tactivin was observed in 70% of patients during 2 months. 30% of patients needed a second course of treatment of recover normal immunological and clinical indices. The treatment with tactivin of IHD patients must be combined with application of routine antianginal drugs.


A sensitive assay for the quantification of reverse transcriptase activity based on the use of carrier-bound template and non-radioactive-product detection, with special reference to human-immunodeficiency-virus isolation.
A non-radioactive 96-well microtitre plate reverse transcriptase (RT) assay, based on the use of covalently bound riboadenosine homopolymer in the wells and 5-bromodeoxyuridined 5'-triphosphate (BrdUTP) as dNTP, is described. The whole assay is performed in a single well, including the quantitative detection of incorporated BrdU, which is performed immunologically using alkaline phosphatase-conjugated anti-BrdU antibody and colorometric reading. The system also allows the use of variable amounts of primer. The kinetics and characteristics of the assay using BrdUTP is similar to the use of [3H]dTTP. The sensitivity of the assay can be varied either by altering the duration of RT assay time and/or by prolonging the alkaline phosphatase reaction. Thus the assay can detect < 0.02 pg of recombinant human-immunodeficiency-virus (HIV) type I RT, < 0.005 m unit of avian-myeloblastosis-virus RT or < 0.02 m unit of recombinant Moloney-murine-leukaemia-virus RT. The assay was found to be useful with various types of cell-culture material, and a comparative study of 16 HIV-infected lymphocyte cultures, using 10 microliters of supernatant medium for RT assay and 22.5 microliters for p24 antigen assay showed that the new RT assay was at least 25-fold more sensitive than the p24 antigen assay. The results also show a good correlation between the RT activities found and the p24-antigen level detected, with exception for HIV2 isolates, as they only became positive in the RT assay. The technical performance and the capacity of the test compared with other available RT kits is discussed, as well as its use for other applications.


Transcriptome analyses reveal transcriptional profiles of horse oocytes before and after in vitro maturation.
Oocyte in vitro maturation is necessary for the study and application of animal-assisted reproduction technology in animal reproduction and breeding. The comprehensive transcriptional profile of equine oocyte maturated in vitro has not been fully mined yet, which makes many key transcriptional events still unidentified. Here, Smart-seq2 was performed to analyse the gene expression pattern and the underlying regulatory mechanism of horse germinal vesicle (GV) and in vitro metaphase II (MII) oocytes. The results showed that 6402 genes (2640 up-regulated and 3762 down-regulated in MII samples compared to GV) and 4021 lncRNA transcripts (1210 up-regulated and 2811 down-regulated in MII samples compared to GV) were differentially expressed in GV and MII oocytes. Further, GO and KEGG analysis found that differentially expressed mRNAs and lncRNAs were mainly enriched in the pathways related to energy and lipid metabolism. In addition, LGALS3 was found a key gene in mediating the regulation of oocyte meiosis recovery and fertilization ability. This study provides novel knowledge about gene expression and energy metabolism during equine oocyte maturation and a reference for the further study and application of assisted reproductive technology in horse reproduction and breeding.


Comparison of three lasers for dental instrument sterilization.
The sterilization of dental instruments is an area of great interest and recent concern in the field of dentistry. The purpose of this study was to compare the ability of three lasers (argon, CO2, and NdYAG) to sterilize dental instruments. Endodontic reamers were contaminated with microorganisms, lased at various levels of energy, placed in Trypticase soy broth, incubated, and read for growth or no growth to determine sterility. Results indicated that the argon laser is capable of sterilizing selected dental instruments at the lowest energy level (1 watt for 120 seconds) of the three lasers tested. The other two lasers were able to sterilize the instruments also, but at higher energy levels. Results indicated all three lasers capable of sterilizing selected dental instruments; however, the argon laser was able to do so consistently at the lowest energy level of 1 watt for 120 seconds.


Rapid Visual Detection of Hepatitis C Virus Using Reverse Transcription Recombinase-Aided Amplification-Lateral Flow Dipstick.
Hepatitis C virus (HCV) infection is a global public health threat. Reaching the World Health Organization's objective for eliminating viral hepatitis by 2030 will require a precise disease diagnosis. While immunoassays and qPCR play a significant role in detecting HCV, rapid and accurate point-of-care testing is important for pathogen identification. This study establishes a reverse transcription recombinase-aided amplification-lateral flow dipstick (RT-RAA-LFD) assay to detect HCV. The intact workflow was completed within 30 min, and the detection limit for synthesized C/E1 plasmid gene-containing plasmid was 10 copies/μl. In addition, the test showed good specificity, with no cross-reactivity observed for hepatitis A virus, hepatitis B virus, HIV, syphilis, and human papillomavirus virus. Using extracted RNAs from 46 anti-HCV antibody-positive samples, RT-RAA-LFD showed 100% positive and negative concordance rates with qPCR. In summary, the RT-RAA-LFD assay established in this study is suitable for the rapid clinical detection of HCV at the community level and in remote areas.


Why a Condensate Can Be Thought of as Having a Definite Phase.
We present an argument for assigning a definite phase to an assembly of Bose-Einstein Condensed atoms. This relies on the demonstration that a coherent state of the condensed system is a robust state in the presence of interactions between the condensate and its environment.