Sigma receptor ligands: applications in inflammation and oncology.
Sigma (sigma) receptors were initially proposed as a subtype of opiate receptors, and bind several psychoactive compounds. They are classified into sigma 1 (sigma1) and sigma 2 (sigma2) subtypes. The characterization of these subunits, and the discovery of new specific sigma receptor ligands, demonstrated that sigma receptors belong to a specific entity distinct from opiate receptors. Radioligand-binding data have recently demonstrated that the sigma1 subtype is related to a sterol isomerase, which is involved in the cholesterol biosynthesis pathway, and also to another protein of unknown function, SRBP2 (SR-31747 binding-protein 2), which shares a high homology with this enzyme. This complex group of proteins also binds molecules devoid of central effect, which demonstrate potent anti-inflammatory properties, and so are potentially useful in pathologies where pro-inflammatory cytokines are involved, particularly rheumatoid arthritis, Crohn's disease or psoriasis. In addition, the two sigma receptor subtypes and their two related proteins are also expressed on tumor cells, where they could be of prognostic relevance, and their ligands could potentially be used in the detection and targeting of tumors.


Oral contrast agents for small bowel MRI: comparison of different additives to optimize bowel distension.
The purpose of this study was to compare two osmotic carbohydrate sugar alcohols (mannitol 2.5% and sorbitol 2.5%, 2.0%, and 1.5% watery solutions) in combination with 0.2% locust bean gum (LBG) for small bowel distension for MR imaging. Small bowel distension was quantified on coronal 2D TrueFISP images by measuring the diameters of 16 small bowel loops in each of 12 healthy subjects (age range 31-55 years). Additionally, the grade of small bowel distension was rated qualitatively. Patient acceptance concerning nausea, vomiting, flatulence, and diarrhea was noted for each solution, and all results were compared by a Wilcoxon test or t test, respectively. The ingestion of water combined with LBG and either 2.5% mannitol or 2.0% sorbitol showed the best distension of the small bowel. The lowest side effect rate was observed following ingestion of sorbitol in a concentration of 2.0 and 1.5%. Based on these data, we recommend a combination of LBG and 2% sorbitol use for optimal bowel distension and minimal side effects resulting in enhanced patient acceptance.


A preliminary study of the effects of cochlear implants on the production of sibilants.
The potential influence of auditory information in the production of /s/ and /integral of/ was explored for postlingually deafened adults with four-channel Ineraid cochlear implants. Analyses of the spectra of the sibilant sounds were compared for speech obtained prior to implant activation, after early implant use and after 6 months of use. In addition, the output of the Ineraid device (measured at each of the four electrodes) was analyzed with pre- and postactivation speech samples to explore whether the speech production changes were potentially audible to the cochlear-implant user. Results indicated that subjects who showed abnormally low or incorrect contrast between /s/ and /integral of/ preactivation, and who received significant auditory benefit from their implants were able to increase the distinctiveness of their productions of the two speech sounds.


[Monozygotic twins with centrotemporal spikes on the electroencephalogram--differences in clinical manifestations and the effect of valproate therapy].
Monozygotic twin sisters who had almost identical electroencephalographic abnormalities, but different clinical features and different response of this abnormalities to valproate at the age of 6 years are described. One twin was admitted to the hospital because of numerous brief myotonic seizures of sudden onset with corresponding abnormalities in the electroencephalogram. The seizures disappeared completely and the electroencephalogram became normal within a week of treatment with valproate. The other twin never had any seizures. However, her electroencephalogram repeatedly showed impressive abnormalities and the therapy with valproate had no substantial effect on these abnormalities. We believe this twins to be a suitable model for studying the inheritance of epilepsy and electroencephalographic abnormalities, as well as for studying the action of antiepileptic drugs. At this moment, it is not possible to offer any reasonable explanation for the normalization of the electroencephalographic abnormality during valproate treatment in the clinically affected twin, while the electroencephalogram remained abnormal in the clinically unaffected twin.


Selection of cancer cells with repressed mitochondria triggers colon cancer progression.
The contribution that mitochondrial bioenergetics could have in cancer development is debated. Here, we have generated HCT116-derived colocarcinoma cell lines expressing different levels of the beta catalytic subunit of the mitochondrial H+-adenosine triphosphate synthase to assess the contribution of mitochondrial bioenergetics in colon cancer progression. The generated cells exhibit large ultrastructural, transcriptomic, proteomic and functional differences in their mitochondria and in their in vivo tumor forming capacity. We show that the activity of oxidative phosphorylation defines the rate of glucose utilization by aerobic glycolysis. The aggressive cellular phenotype, which is highly glycolytic, is bound to the deregulated expression of genes involved in metabolic processes, the regulation of the cell cycle, apoptosis, angiogenesis and cell adhesion. Remarkably, the molecular and ultrastructural analysis of the tumors derived from the three HCT116 cell lines under study highlight that tumor promotion inevitably requires the selection of cancer cells with a repressed biogenesis and functional activity of mitochondria, i.e. the highly glycolytic phenotype is selected for tumor development. The tumor forming potential of the cells is a non-genetically acquired condition that provides the cancer cell with a cell-death resistant phenotype. An abrogated mitochondrial respiration contributes to a diminished potential for reactive oxygen species signaling in response to 5-fluorouracil treatment. Treatment of cancer cells with dichloroacetate partially restores the functional differentiation of mitochondria and promotes tumor regression, emphasizing the reversible nature of the metabolic trait of cancer.


Myopia in preterm children at 12 to 24 months of age.
To examine biometric factors that may influence the high incidence of myopia in pre-term children at 12 to 24 months of age. Fifty eyes of 25 patients with myopia and 70 eyes of 35 patients with emmetropia at 12 to 24 months of age were selected from a group of preterm children who had been screened for retinopathy of prematurity and returned for follow-up examinations. Forty eyes of 20 full-term children of the same age were also included in the study as a control group. A-scan ultrasonography was performed to measure axial length, lens thickness, and anterior chamber depth in the three groups. The myopic group had a significantly greater axial length than did the other groups. However, the three groups did not differ in lens thickness or anterior chamber depth. The degree of myopia increased with the increase in axial length and the decrease in anterior chamber depth. The development of myopia in preterm children 12 to 24 months of age appears to be influenced mainly by axial length, whereas the degree of myopia seems to be related to axial length and anterior chamber depth. Among refractive components, axial length plays a major role in myopia occurring at this age in preterm patients.


Changes in intracellular calcium concentration in bovine oocytes following penetration by spermatozoa.
The pattern of changes in intracellular calcium concentration ([Ca2+]i) in bovine oocytes after penetration by spermatozoa was determined. Dynamic video imaging, using Fura-2 as a probe for intracellular free calcium, showed that activation of oocytes by spermatozoa induced multiple transient increases in [Ca2+]i with a spike interval of 24.2 +/- 7.3 min, and that the early transient increases were propagated throughout the oocytes in the form of a wave. Calcium transients at fertilization are involved in the induction of cortical granule exocytosis and the resultant block to polyspermy. The hypothesis that the inhibition of Ca2+ release from inositol trisphosphate-sensitive stores would inhibit exocytosis and increase polyspermy was tested by injecting oocytes before fertilization with heparin, a potent inhibitor of inositol trisphosphate-activated Ca2+ release. There was no significant difference after fertilization in either [Ca2+]i spikes or in polyspermy rates between control and experimental groups injected with low molecular mass heparin up to a final cytoplasmic concentration of 400 mumol l-1. We conclude that inositol trisphosphate-independent Ca2+ stores may be mobilized during the fertilization of bovine oocytes.


Chest high resolution computed tomography findings in connective tissue diseases.
Lung disorders are important for prognosis of connective tissue disease (CTD). Thus, chest radiography, High Resolution Computed Tomography (HRCT) of the chest and ultrasonic echocardiogram are suggested after the diagnosis of these conditions. The purpose of this study was to evaluate chest HRCT findings in patients with CTD. In this descriptive cross-sectional study, we evaluated HRCT findings in patients with (CTD) hospitalized in Imam Reza Hospital in Mashhad from 2006 - 2011. Patients' age, sex, type of rheumatic disease and HRCT results were collected and analyzed by SPSS version 16.0 software. Out of 75 patients (78.67% females, 21.33% males with a mean age of 41.6 years), 56% had respiratory symptoms. Scleroderma was the most common disease (38.6%) followed by rheumatoid arthritis (26.6%) and systemic lupus erythematosus (14.6%). Interstitial tissue involvement of the lung was the most frequent finding in patients with scleroderma, dermatomyositis, polymyositis and Sjogren's syndrome (48.3%, 57.1%, 60% and 66.7%, respectively). Pleural thickening was the most common finding in patients with rheumatoid arthritis (45%). Pleural effusion was the most frequent finding in patients with systemic lupus erythematosus (45.4%). Lymphadenopathy and bronchiectasis had the lowest prevalence (1.3%). Our data shows that interstitial tissue involvement, pleural thickening and pleural effusion are common in patients with rheumatic diseases which is consistent with some previous studies.


Transcriptional control of lignin biosynthesis by tobacco LIM protein.
Lignin is a complex phenolic plant polymer that is essential for mechanical support, defense, and water transport in higher plants. The AC-rich motif, Pal-box is an important cis-acting element for gene expression in phenylpropanoid biosynthesis. We isolated a cDNA clone (Ntlim1) encoding a Pal-box binding protein by Southwestern screening. The deduced amino acid sequence of Ntlim1 is highly similar to members of the LIM protein family that contain a zinc finger motif. Moreover, Ntlim1 had a specific DNA-binding ability and transiently activated transcription of a beta-glucuronidase reporter gene driven by the Pal-box sequence. The results of transient expression assays with tobacco cultured cells showed that fusion proteins between GFP and Ntlim1 can enter nuclei. Transgenic tobacco plants with antisense Ntlim1 showed low levels of transcripts from some key phenylpropanoid pathway genes such as phenylalanine ammonia-lyase, hydroxycinnamate CoA ligase and cinnamyl alcohol dehydrogenase. Furthermore, a greater than 20% reduction in lignin content was observed in transgenic tobacco with antisense Ntlim1.


Application of electroabsorption techniques to the study of crystal particles in glasses.
Glasses containing a small amount of CdS have an optical absorption edge which depends upon the heat treatment accorded the glass. The edge position agrees roughly with that of CdS crystals. Data for two glasses with absorption edges at about 2.45 eV and 2.52 eV are presented. The optical absorption spectra of such glasses have been modulated by application of ac electric fields. The spectral dependence of the modulated component of the absorption coefficient is strikingly different for glasses with different heat treatments. This difference is interpreted in terms of excitons and the crystal particle sizes and gives a consistent explanation of the shift in the absorption edge. Since the absorption edge in CdS crystals is due to excitons, it is suggested that the lower energy absorption edge results from crystal particle sizes large enough to permit exciton formation, whereas the higher energy edge results from smaller particle sizes that do not permit exciton formation. The electroabsorption spectrum for the glass with the lower energy edge qualitatively resembles the spectrum for CdS films, whose salient features are attributed to excitons.


A pilot study of subcutaneous decitabine in β-thalassemia intermedia.
Ineffective erythropoiesis, the hallmark of β-thalassemia, is a result of α/non-α globin chain imbalance. One strategy to redress globin-chain imbalance is to induce γ-globin gene (HBG) expression. Repression of HBG in adult erythroid cells involves DNA methylation and other epigenetic changes. Therefore, the cytosine analog decitabine, which can deplete DNA methyltransferase 1 (DNMT1), can potentially activate HBG. In 5 patients with β-thalassemia intermedia, a dose and schedule of decitabine intended to deplete DNMT1 without causing significant cytotoxicity (0.2 mg/kg subcutaneous 2 times per week for 12 weeks) increased total hemoglobin from 7.88 ± 0.88 g/dL to 9.04 ± 0.77 g/dL (P = .004) and absolute fetal hemoglobin from 3.64 ± 1.13 g/dL to 4.29 ± 1.13 g/dL (P = .003). Significant favorable changes also occurred in indices of hemolysis and red blood cell densitometry. Consistent with a noncytotoxic, differentiation altering mechanism of action, the major side effect was an asymptomatic increase in platelet counts without erythrocyte micronucleus or VDJ recombination assay evidence of genotoxicity. This study was registered at www.clinicaltrials.gov as #NCT00661726.


VSG gene expression site control in insect form Trypanosoma brucei.
When the African trypanosome Trypanosoma brucei is taken up from mammals by a tse-tse fly, it replaces its variant surface glycoprotein (VSG) coat by a procyclin coat. Transcription of VSG genes stops in the fly, but transcription of sequences derived from the promoter area of the VSG expression site(s) remains high. Whether this is due to continuing high activity of one promoter or to low activity of many promoters was unclear. We have used the small differences between the sequences of different expression sites to show that multiple expression site promoters are active in insect form trypanosomes. This is confirmed by the low expression of single copy marker genes introduced into the transcribed area. However, if the expression site promoter is removed from the genomic location of the expression site and inserted in the non-transcribed spacer of the ribosomal DNA (rDNA), it is derepressed. Derepression of transcription can also be accomplished by replacing the promoter of an expression site by an rDNA promoter. We conclude that the down-regulation of VSG gene expression site promoters in insect form trypanosomes is affected by both the DNA sequence of the promoter and the genomic context in which it resides.


CD4-positive effector memory T cells participate in disease expression in ANCA-associated vasculitis.
Although the cause of ANCA-associated vasculitis (AAV) remains undetermined, the presence of lymphocytic infiltrates in inflammatory lesions of patients suggests that vascular damage is immune mediated. Studies over the past decade have implicated a role for T cells in the pathogenesis of AAV as altered T cell phenotype has been observed in this disorder. The distribution of T cell subpopulations has been analyzed most intensely in Wegener's granulomatosis (WG), where an expanded population of circulating CD4(+) effector memory T cells (CD4(+)T(EM)) was demonstrated. CD4(+)T(EM) cells play a major role in the pathogenesis of several autoimmune diseases. Specific suppression of CD4(+)T(EM) cells inhibits delayed-type hypersensitivity (DTH) and has therapeutic potential in autoimmune disease. Thus, CD4(+)T(EM) cells may act as inducers of tissue injury and participate in the development of AAV. Therapies that target CD4(+)T(EM), without impairing the activity of other lymphocyte subsets, may hold therapeutic promise for AAV.


[Angiotensin II up-regulates expression of inducible nitric oxide synthase in human umbilical endothelial cells: roles of AT1 and AT2].
Angiotensin II is an important pro inflammation factor in the cardiovascular system. This experiment is aimed to study the effects of angiotensin II on inducible nitric oxide synthase expression in human umbilical endothelial cells. Human umbilical endothelial cells were cultured in vitro and treated with angiotensin II alone or in combination with AT1, AT2 and NF-kappaB inhibitors respectively. The inducible nitric oxide synthase expressions at protein and mRNA levels were measured with Western blot and reverse transcription-polymerase chain reaction (RT-PCR), and the activity of NF-kappaB was analyzed with EMSA. Angiotensin II up-regulated inducible nitric oxide synthase expressions at the protein and mRNA levels at 5 h (P < 0.05), the activity of NF-kappaB was enhanced at 2 h (P < 0.05). These effects could be blocked by AT1 and NF-kappaB inhibitors but not by AT2 inhibitor. Angiotensin II can upregulate the expression of inducible nitric oxide synthase through NF-kappaB pathway in human umbilical endothelial cells. AT1, other than AT2, play a key role in this process.


Clinical practice in management of hydration for lung cancer patients receiving cisplatin-based chemotherapy in Japan: a questionnaire survey.
A questionnaire survey was performed to investigate the actual hydration methods used with cisplatin-containing regimens at various institutions in Japan to gain an overview of the varieties employed. Replies were received from 368 of 686 institutions board-certified by the Japanese Respiratory Society. In 233 institutions (63%), new lung cancer patients were treated regularly with regimens containing cisplatin at ≥60 mg/m2. In 172 institutions (48%), hydration with <3000 ml of intravenous saline was performed on day 1. In 225 institutions (65%), hydration was performed for up to 3 days at most, but no more than 48 (14%) of the institutions that responded did so on day 1 only. Two to three weeks of hospitalization was needed for the initial course at most institutions (76%). Thirteen institutions (4%) treated patients as outpatients after the second course, whereas none did so from the beginning of treatment. Despite inconsistencies among the methods used by the various institutions, 84% of those surveyed considered their approaches to be appropriate. Some useful objective indices for deciding the volume or duration of hydration are needed.


Capsaicin, a Powerful •OH-Inactivating Ligand.
Oxidative conditions are frequently enhanced by the presence of redox metal ions. In this study, the role of capsaicin (8-methyl-N-vanillyl-6-nonenamide, CAP) in copper-induced oxidative stress was investigated using density functional theory simulations. It was found that CAP has the capability to chelate Cu(II), leading to complexes that are harder to reduce than free Cu(II). CAP fully turns off the Cu(II) reduction by Asc-, and slows down the reduction in this cation by O2•-. Therefore, CAP is proposed as an •OH-inactivating ligand by impeding the reduction in metal ions (OIL-1), hindering the production of •OH via Fenton-like reactions, at physiological pH. CAP is also predicted to be an excellent antioxidant as a scavenger of •OH, yielded through Fenton-like reactions (OIL-2). The reactions between CAP-Cu(II) chelates and •OH were estimated to be diffusion-limited. Thus, these chelates are capable of deactivating this dangerous radical immediately after being formed by Fenton-like reactions.


High-level coordination and strategy in the 2007 equine influenza outbreak response.
The equine influenza (EI) outbreak presented many challenges that required high-level coordination and decision making, as well as the development of new approaches for satisfactory and consistent resolution. This paper outlines the elements of the national coordination arrangements, preparatory arrangements in place prior to the outbreak that facilitated national coordination, and some of the issues faced and resolved in the response.


Regulation of phosphoribosyl ubiquitination by a calmodulin-dependent glutamylase.
The bacterial pathogen Legionella pneumophila creates an intracellular niche permissive for its replication by extensively modulating host-cell functions using hundreds of effector proteins delivered by its Dot/Icm secretion system1. Among these, members of the SidE family (SidEs) regulate several cellular processes through a unique phosphoribosyl ubiquitination mechanism that bypasses the canonical ubiquitination machinery2-4. The activity of SidEs is regulated by another Dot/Icm effector known as SidJ5; however, the mechanism of this regulation is not completely understood6,7. Here we demonstrate that SidJ inhibits the activity of SidEs by inducing the covalent attachment of glutamate moieties to SdeA-a member of the SidE family-at E860, one of the catalytic residues that is required for the mono-ADP-ribosyltransferase activity involved in ubiquitin activation2. This inhibition by SidJ is spatially restricted in host cells because its activity requires the eukaryote-specific protein calmodulin (CaM). We solved a structure of SidJ-CaM in complex with AMP and found that the ATP used in this reaction is cleaved at the α-phosphate position by SidJ, which-in the absence of glutamate or modifiable SdeA-undergoes self-AMPylation. Our results reveal a mechanism of regulation in bacterial pathogenicity in which a glutamylation reaction that inhibits the activity of virulence factors is activated by host-factor-dependent acyl-adenylation.


[Fiber gastroscopy in the diagnosis of gastroduodenal diseases and of primary cancer of the gastric stump in particular].
Data available in the literature are adduced and personal experience recorded with 5930 fiber gastroscopies, leading to the conclusion that fiber gastroscopy is a valuable method for diagnosis of diseases of the upper part of the gastrointestinal tract. Some aspects of primary cancer of the gastric residue and its inevitable accompanying pathology--the gastroduodenal reflux--are discussed, analyzing 313 fiber gastroscopies of patients, who had undergone in the past gastric resection for benign diseases. The authors adduce motives for the need of periodic fiber gastroscopic control of operated patients, aimed at early prophylaxis of primary cancer of the gastric residue. The need of regular medical control on these patients is also emphasized.


Enzymatic kinetic resolution of internal propargylic diols. Part I: a new approach for the synthesis of (S)-pent-2-yn-1,4-diol, a natural product from Clitocybe catinus.
Internal bis-substituted propargylic diols were subjected to enzymatic kinetic resolution promoted by CAL-B. Employing a two round sequence EKR, mono- and bis-acetoxy propargylic products were obtained in a high enantiomeric ratio (E > 200). The efficiently resolved chiral 8b was applied in a concise synthesis of (S)-1b, an optically active natural product produced by fungi Clitocybe catinus.


Pulmonary emboli from blood-biomaterial interaction.
The problem of surface thrombosis and subsequent embolization remains entrenched as a yet incompletely surmounted barrier to the development of truly satisfactory intravascular prosthetic devices. A baboon ex vivo shunt was used to determine the interaction of Indium-111 platelets and potential biomaterials. The uptake of Indium-111 platelets was monitored continuously by gamma camera scanning. Several of the materials tested demonstrated a saw-toothed pattern of platelet activity, with accumulation followed by rapid decline. Neither PTFE nor Dacron exhibited this pattern. Post shunt scans of the animals' chests showed discrete foci of platelet activity in the lungs, corresponding to each embolic event noted on the material's scan. In conclusion, the search for a smooth surface as a blood material interface may produce a material which accumulates and then sloughs significant platelet aggregates. It is crucial that these materials be subjected to vigorous testing to determine their safety prior to initiation of clinical trials.


Inhibition of prolactin secretion by nomifensine in man.
Serum prolactin, TSH and GH levels were measured in thirty healthy volunteers in fasting conditions and following oral administration of 200 mg nomifensine. In addition, the effect of the drug on serum prolactin and TSH response to synthetic TRH was studied in twenty normal subjects. Inhibition of endogenous catecholamine reuptake by nomifensine significantly inhibited prolactin release whereas it had no effect on TSH and GH levels. Nomifensine administration had no appreciable effect on the TRH-induced release of TSH and prolactin.


Holographic laser beam deflector.
A mechanically rotating laser beam deflector is described that consists of several transmission type volume holograms recorded on a cylindrical surface. Its performance characteristics are compared with those of a multifacetted rotating mirror.


Chronic exposure to U18666A is associated with oxidative stress in cultured murine cortical neurons.
Findings that antioxidant treatment may be beneficial in Alzheimer's disease indicate that oxidative stress is an important factor in its pathogenesis. Studies have also suggested that cholesterol imbalance in the brain might be related to the development of neurological disorders. Previously, we have reported that U18666A, a cholesterol transport-inhibiting agent, leads to apoptosis and intracellular cholesterol accumulation in primary cortical neurons. In this study, we found that neuronal apoptosis mediated by U18666A is associated with oxidative stress in the treated cortical neurons. Cortical neurons treated with U18666A also showed decreased secretion and increased intraneuronal accumulation of beta-amyloid. The association of neuronal apoptosis with oxidative stress and Abeta accumulation may provide clues to the pathogenesis of Alzheimer's disease, as well as the role oxidative stress plays in other neurodegenerative diseases.


A new technique based on Artificial Bee Colony Algorithm for optimal sizing of stand-alone photovoltaic system.
One of the most recent optimization techniques applied to the optimal design of photovoltaic system to supply an isolated load demand is the Artificial Bee Colony Algorithm (ABC). The proposed methodology is applied to optimize the cost of the PV system including photovoltaic, a battery bank, a battery charger controller, and inverter. Two objective functions are proposed: the first one is the PV module output power which is to be maximized and the second one is the life cycle cost (LCC) which is to be minimized. The analysis is performed based on measured solar radiation and ambient temperature measured at Helwan city, Egypt. A comparison between ABC algorithm and Genetic Algorithm (GA) optimal results is done. Another location is selected which is Zagazig city to check the validity of ABC algorithm in any location. The ABC is more optimal than GA. The results encouraged the use of the PV systems to electrify the rural sites of Egypt.


Coronary heart disease knowledge tool for women.
To develop a tool that measures coronary heart disease (CHD) knowledge specifically for women. The new CHD knowledge tool, based on previous surveys of women's CHD knowledge, has 25 multiple-choice questions. An expert panel evaluated content and face validity. The tool was pilot tested in women without CHD, who were admitted to a Chest Pain Center. The tool was subsequently administered to laywomen and female cardiovascular nurses to evaluate its validity and reliability. The sample included 49 women as the control group (Group 1), 23 cardiovascular nurses as a known group (Group 2), and 22 women with an educational program as the treatment group (Group 3). Knowledge of women in Group 1 was compared with Groups 2 and 3 in known group and predictive validity tests. The new tool demonstrates good validity and reliability to measure CHD knowledge in women. Women continue to have low CHD knowledge, and nurse practitioners should provide education to improve women's CHD knowledge as a strategy to promote healthy lifestyle practices and CHD risk prevention. The new tool can be utilized in future research to measure women's CHD knowledge.


[Two cases of inoperable advanced bileduct cancer treated effectively with a gemcitabine/cisplatin combination].
We report two cases of inoperable advanced bileduct cancer that responded well to combined gemcitabine (GEM)/cisplatin (CDDP) therapy. A 70-year-old woman was admitted to the hospital because of jaundice; PTCD was performed, followed by laparotomy, however, the tumor was found to be inoperable because of extensive direct invasion of the surrounding organs. Then, after insertion of a stent, the patient was started on combined chemotherapy with GEM 1,000 mg/m2 on days 1, 8 and CDDP 70 mg/m2 on day 1 administered once every 3 weeks. After 4 courses, thrombocytopenia appeared. Therefore, chemotherapy was continued for another three courses with GEM 800 mg/m2 on days 1, 15 and CDDP 50 mg/m2 on day 1 every 4 weeks. After 7 courses the serum CEA level returned to normal range, and marked reduction of the tumor size was observed on CT. The patient has been able to maintain a good quality of life without occurrence of any severe adverse effects. A 61-year-old woman was admitted to the hospital because of icterus, and was diagnosed to have lower bile duct cancer with liver metastasis. After insertion of a stent, she was started on combined chemotherapy with GEM 1,000 mg/m2 on days 1, 8 and CDDP 70 mg/m2 on day 1 administered once every 3 weeks. After completion of 4 courses, the patient developed thrombocytopenia and a feel- ing of dullness. Therefore, chemotherapy was continued for the next three courses with GEM 800 mg/m2 on days 1, 15 and CDDP 50 mg/m2 on day 1, administered every 4 weeks. This treatment was associated with a fall of the serum CA19-9 level to within normal range, and marked improvement of the liver metastasis was also noted. Combined GEM/ CDDP therapy improves the QOL of inoperable bile duct cancer patients and offers promise as pre-operative chemotherapy.


[Impact of neurobiofeedback by beta rhythm of the brain on the functional state of cardiovascular system of athletes with different motor activity].
Recovery of athletes after strenuous muscular activity is one of the most up-to-date trends in current sports medicine. Therefore, neurobiofeedback technology, a complex of ideas for methods, based on biological feedback, is sufficiently promising. Available studies of neurobiofeedback by beta rhythm use in clinical medicine indicate a powerful therapeutic and rehabilitative potential of the method with pronounced correction of higher mental functions activity, volitional control and voluntary regulation of activity. To examine the impact of one procedure of neurobiofeedback by beta rhythm of the brain on the cardiovascular system functional state in the athletes with different character of motor activity. The study included 1020 male athletes aged 18-21 years. Depending on the motor activity, patients were divided into 5 groups: 1st group - cyclic sports athletes (38%); 2nd group - speed-power sports athletes (25%); 3rd group - combat sport athletes (3%); 4th group - team sports athletes (17%) and 5th group - athletes of complex coordination sports (17%). The procedure of neurobiofeedback by beta rhythm of the brain was done in the conditions of active waking at open eyes. Registration of bioelectric activity of the brain and training on beta rhythm were done in the Fz-Cz lead by the international system «10-20» with the arrangement of indifferent electrode on the earlobe of the subjects (PAC «BOSLAB», Institute of Molecular Biology and Biophysics, Novosibirsk, Russia). Heterochronic pattern of changes in the indicators of systemic pressure, cardiac and vascular activity of the athletes' body during a single procedure of neurobiofeedback by beta rhythm of the brain in the preparation period of the training process, depending on the character of athletic activities, was found. In response to the impact, the following indicators have changed significantly: heart rate and index of functional changes in combat sport athletes (3rd group); stroke and cardiac output in all groups. Cardiovascular regulation index and specific peripheral vascular resistance significantly increased in the groups 2-5. Cardiac index significantly decreased in the groups 1, 2, 4 and 5. Qualitative changes in types of blood circulation occurred in all groups: in groups 1, 3 and 5 - from hyperkinetic to eukinetic, in group 2 - from hyperkinetic to hypokinetic, in group 4 - from eukinetic to hypokinetic, contributing to the economization of cardiovascular activity function. The use of neurobiofeedback by the beta rhythm of the brain in the practice of sports medicine requires additional detailed research of the features and development of individual methods depending on the type of athletic activity, features of cardiac activity regulation, etc.


[Therapeutic education in oncology: involving patient in the management of cancer].
The notion of therapeutic education was only recently introduced in cancer. Although the term is commonly used, no standard definition exists for the concept and principles of therapeutic education and its efficacy remains to be assessed. Therapeutic education is complementary to the healthcare approach and aims to get the patients more involved in their disease and the treatment decision-making process. This discipline, placed at the interface of human and social sciences, was first developed for the management of chronic diseases (diabetes, asthma). It derives from the principle that involving patients in their own care and management can help them better adjust to life with a chronic disease. The lengthening survival time of cancer patients, which contributes to making cancer a chronic disease, as well as changes in the patient-caregiver relationship contribute to the development of therapeutic education in cancer. Pilot studies, conducted principally in the United States, evaluating the side effects of chemotherapy and the management of pain, have demonstrated that such educational programs could improve patient quality of life and decrease the side effects of treatments. The success of these programs depends on several parameters: taking into account patient's opinion in the elaboration and preparation of the programs; involving skilled multidisciplinary teams engaged in iterative educational actions; having recourse to methodological tools to evaluate the impact of implemented programs. Consistent with the World Health Organization guidelines, research should be conducted in France in order to elaborate and implement cancer-specific education programs and evaluate their potential benefit. Patient education programs on pain, fatigue, nutrition and treatment compliance are currently being developed at Saint-Etienne Regional Resource Centre for cancer information, prevention and education, within the framework of the Canceropole Lyon Auvergne Rhône-Alpes.


The impact of COVID-19 on patients with neurological disorders and their access to healthcare in Africa: A review of the literature.
The coronavirus disease 2019 (COVID-19) pandemic has hampered the progress of neurological healthcare services for patients across Africa. Before the pandemic, access to these services was already limited due to elevated treatment costs among uninsured individuals, shortage of medicines, equipment, and qualified personnel, immense distance between residing areas and neurological facilities, and a limited understanding of neurological diseases and their presentation by both the health workers and the African population. The databases PubMed, Google Scholar, Science Direct, and the National Library of Medicine were searched for literature. All articles on neurological disorders in Africa were considered. This review article explores the challenges of providing the best services for patients suffering from neurological disorders in Africa amid the COVID-19 pandemic and provides evidence-based recommendations. As Africa's governments made more resources available to support patients affected by COVID-19, neurological care received less priority and the capacity and competency to treat patients with neurological disorders thus suffered substantially. Both short-term and long-term strategies are needed to improve the quality of neurological services after the pandemic in the region. To strengthen Africa's neurological services capability during and after the COVID-19 pandemic, African governments must ensure appropriate healthcare resource allocation, perform neurology management training, and increase health security measures in medication supply. Long-term strategies include incorporating responsible finance and resource procurement and advancement of tele-neurology. International collaboration is essential to promote the sustainable improvement of neurological services in Africa.


LiSSA: Localized Stochastic Sensitive Autoencoders.
The training of autoencoder (AE) focuses on the selection of connection weights via a minimization of both the training error and a regularized term. However, the ultimate goal of AE training is to autoencode future unseen samples correctly (i.e., good generalization). Minimizing the training error with different regularized terms only indirectly minimizes the generalization error. Moreover, the trained model may not be robust to small perturbations of inputs which may lead to a poor generalization capability. In this paper, we propose a localized stochastic sensitive AE (LiSSA) to enhance the robustness of AE with respect to input perturbations. With the local stochastic sensitivity regularization, LiSSA reduces sensitivity to unseen samples with small differences (perturbations) from training samples. Meanwhile, LiSSA preserves the local connectivity from the original input space to the representation space that learns a more robustness features (intermediate representation) for unseen samples. The classifier using these learned features yields a better generalization capability. Extensive experimental results on 36 benchmarking datasets indicate that LiSSA outperforms several classical and recent AE training methods significantly on classification tasks.


[The inhibition effects of apatinib on cell proliferation, migration and apoptosis in esophageal carcinoma via Ras/Raf/MEK/ERK and JAK2/STAT3 pathways].
Objective: To investigate the in vitro and in vivo effects of apatinib in esophageal squamous cell carcinoma and the underlying mechanisms. Methods: The esophageal cancer cells, KYSE-150 and ECA-109, were divided into control group and apatinib treatment group at the concentrations of 2.5, 5, 10, 20 and 40 μmol/L respectively. All of experiments were performed in triplicate. MTT and colony formation assays were used to measure cell proliferation. Transwell assay was used to determine the migration capacity. The effect of apatinib on cell cycle and apoptosis was analyzed by flow cytometry. The expression of VEGF and VEGFR-2 was measured by real-time quantitative PCR (qRT-PCR). The concentration of VEGF in the cell supernatant was assessed by enzyme-linked immunosorbent assay (ELISA). The expression levels of MEK, ERK, p-MEK, p-ERK, JAK2, STAT3 and p-STAT3 after VEGF stimulation were detected by Western blot. Furthermore, the nude mice xenograft model was established. The tumor-bearing mice were randomly divided into control group, apatinib low dose treatment group (250 mg) and apatinib high dose treatment group (500 mg), respectively. Tumor inhibition rates of different groups were calculated. And then the expressions of VEGF and VEGFR2 were detected in xenograft tissues by immunohistochemical staining. Results: In the presence of 20 μmol/L and 40 μmol/L of apatinib for 24 hours, the migration cell numbers of KYSE-150 and ECA-109 were 428.67±4.16 and 286.67±1.53 as well as 1 123.67±70.00 and 477.33±26.84, respectively, that were significantly lower than control group (P<0.05 for all). In addition, after treatment with 10 μmol/L, 20 μmol/L and 40 μmol/L of apatinib for 7 days on KYSE-150 and ECA-109, the colony formation rates were (65.12±25.48)%, (58.19±24.73)% and (29.10±22.40)% as well as (70.61±15.14)%, (61.12±17.21)% and (43.09±11.13)%, respectively. The colony formation rates of 20 μmol/L and 40 μmol/L of apatinib treatment groups were significantly lower than control group (100.00±0.00, P<0.05). The cell cycle ratio of G(2)/M phase and apoptosis rate of control group and 20 μmol/L apatinib group in KYSE-150 cells were (12.14±2.13)% and (3.49±0.74)% as well as (26.27±3.30)% and (15.65±1.54)%, respectively. The corresponding ratios in ECA-109 cells were (3.44±0.57)% and (6.31±1.43)% as well as (22.64±2.36)% and (49.26±1.62)%, respectively. The results show that apatinib suppressed cell cycle progression at G(2)/M phase and induced cell apoptosis in both KYSE-150 and ECA-109 cells (P<0.05 for all). In the presence of 20 μmol/L and 40 μmol/L of apatinib in KYSE-150 cells, the relative levels of VEGF mRNA were (42.57±10.43)% and (25.69±1.24)%, and those of VEGF-2 mRNA were (36.09±10.82)% and (13.99±6.54)%, which were all significantly decreased compared to control group (100.00±0.00, P<0.05 for all). For ECA-109 cells, the relative expression of VEGF and VEGFR2 showed similar tendency (P<0.05 for all). Moreover, after treatment with 20 μmol/L and 40 μmol/L of apatinib in KYSE-150 cells, the VEGF concentrations were (766.48±114.27) pg/ml and (497.40±102.18)pg/ml, which were significantly decreased compared to control group [(967.41±57.75) pg/ml, P<0.05)]. The results in ECA-109 were consistent (P<0.05). Furthermore, after treatment with 40 μmol/L of apatinib in KYSE-150 and ECA-109, the relative expression of p-MEK and p-ERK were 0.49±0.05 and 0.28±0.03 as well as 0.63±0.03 and 1.22±0.15, which were significantly lower than control group (1.23±0.19 and 0.66±0.07 as well as 1.03±0.20 and 1.76±0.20; P<0.05). The relative expression of STAT3, p-STAT3 in control group and experimental group were 0.96±0.15 and 0.85±0.16 as well as 0.62±0.09 and 0.36±0.13, respectively. The results showed that the protein levels of STAT3 and p-STAT3 were significantly lower than the control group (P<0.05 for all). The inhibition rates of apatinib in xenograft nude mice were 29.25% and 19.96% for 250 mg and 500 mg treatment groups. The concentration of VEGF were (25.11±4.12) pg/ml, (16.40±2.81) pg/ml and (15.04±4.88)pg/ml for control, 250 mg and 500 mg treatment groups, respectively. Conclusions: Apatinib can inhibit cell proliferation, induce apoptosis and suppress migration of esophageal cancer cells in vitro and in vivo. This effect was mainly mediated via the alterations of Ras/Raf/MEK/ERK pathway and JAK2/STAT3 pathway.


Elementary visual hallucinations in migraine and epilepsy.
A comparison of the elementary visual hallucinations of 50 patients with migraine and 20 patients with occipital epileptic seizures showed that epileptic seizures are predominantly multi-coloured with circular or spherical patterns as opposed to the predominantly black and white linear patterns of migraine. This simple clinical symptom of the elementary visual hallucinations may be helpful in distinguishing between classic or basilar migraine and visual partial epileptic seizures, particularly in children. Claims that epileptic seizures are triggered or caused by migraine may be artificial, reflecting problems in the differential diagnosis between the two diseases.


Molecular detection of HHV-1, HHV-2, HHV-5 and HBV in semen of fertile and infertile men by multiplex PCR method.
A great diversity of factors including viruses such as human herpes virus 1&2 (HHV-1&2), human herpes virus 5 (HHV-5), and hepatitis B virus (HBV) play key roles in sterility and it is worth noting that male infertility accounts for nearly 50% of barrenness, globally. In this regard, we evaluated the prevalence of the aforementioned viruses in semen specimens of two distinct groups of men referred to Novin Infertility Center in Mashhad, Iran. In this cross-sectional study, 300 semen samples were collected from 150 infertile and 150 fertile men. Subsequently, genomic DNA was extracted before performing multiplex polymerase chain reaction (PCR). Eventually, the results were analyzed via SPSS Statistics V.16.0. Out of 300 specimens, 183 (61.1%) were positive at least for one of the forenamed viruses; genome detection of HHV-1&2, HHV-5, and HBV were 27%, 18%, 36.66%, and 4%, respectively. The current study found no correlation between infertility and HBV, HHV-5, and HHV-1&2, which may have to do with factors like sample size, the geographical distribution of the viruses, and the lifestyle (sexual behavior) of the participants. These results emphasize the implementation of such studies on a broader scale to determine the exact factors involved in infertility.


Phytoplankton communities of polar regions--Diversity depending on environmental conditions and chemical anthropopressure.
The polar regions (Arctic and Antarctic) constitute up to 14% of the biosphere and offer some of the coldest and most arid Earth's environments. Nevertheless several oxygenic phototrophs including some higher plants, mosses, lichens, various algal groups and cyanobacteria, survive that harsh climate and create the base of the trophic relationships in fragile ecosystems of polar environments. Ecosystems in polar regions are characterized by low primary productivity and slow growth rates, therefore they are more vulnerable to disturbance, than those in temperate regions. From this reason, chemical contaminants influencing the growth of photoautotrophic producers might induce serious disorders in the integrity of polar ecosystems. However, for a long time these areas were believed to be free of chemical contamination, and relatively protected from widespread anthropogenic pressure, due their remoteness and extreme climate conditions. Nowadays, there is a growing amount of data that prove that xenobiotics are transported thousands of kilometers by the air and ocean currents and then they are deposed in colder regions and accumulate in many environments, including the habitats of marine and freshwater cyanobacteria. Cyanobacteria (blue green algae), as a natural part of phytoplankton assemblages, are globally distributed, but in high polar ecosystems they represent the dominant primary producers. These microorganisms are continuously exposed to various concentration levels of the compounds that are present in their habitats and act as nourishment or the factors influencing the growth and development of cyanobacteria in other way. The most common group of contaminants in Arctic and Antarctic are persistent organic pollutants (POPs), characterized by durability and resistance to degradation. It is important to determine their concentrations in all phytoplankton species cells and in their environment to get to know the possibility of contaminants to transfer to higher trophic levels, considering however that some strains of microalgae are capable of metabolizing xenobiotics, make them less toxic or even remove them from the environment.


Long-term fracture risk following renal transplantation: a population-based study.
Abnormal bone metabolism is a recognized complication of end-stage renal disease, but fracture risk following renal transplantation has not been well quantified. We followed the 86 Olmsted County, Minnesota, residents who underwent initial renal transplantation in 1965-1995 for 911 person-years (median, 10.6 years per subject) in a retrospective cohort study. Fractures, and possible risk factors, were assessed through review of each subject's complete community medical records. Altogether, 117 fractures were observed during follow-up extending to 33 years. The cumulative incidence of any fracture at 15 years was 60% versus 20% expected ( P<0.001). There was a significantly increased risk of fractures generally [standardized incidence ratio (SIR), 4.8; 95% CI, 3.6-6.4] and vertebral (SIR, 23.1; 95% CI, 12.3-39.6) and foot fractures (SIR, 8.4; 95% CI, 5.1-12.9) especially. Age at first transplantation, renal failure due to diabetes, pancreas transplantation, peripheral neuropathy, peripheral vascular disease and blindness were all associated with overall fracture risk. In a multivariate analysis, however, only age and diabetic nephropathy were independent predictors of fracture risk generally, while higher activity status was protective. Diabetes was the only independent predictor of lower limb fractures, whereas age and osteoporosis history predicted vertebral fractures. Cumulative corticosteroid dosage was not associated with increased fracture risk in this analysis. Despite the fact that our patients had few risk factors for preexisting bone disease attendant to postmenopausal osteoporosis, prior corticosteroid use or renal osteodystrophy, these data indicate that renal transplantation is associated with a significant increase in fracture risk among unselected patients in the community. Diabetic patients, particularly, experience excess lower limb fractures. Patients and their care providers should be aware of this elevated fracture risk, which continues long-term.


Purified chick embryo cell (PCEC) rabies vaccine for human use. Laboratory data.
A new inactivated rabies vaccine (Purified Chick Embryo Cell vaccine) for use in humans has been developed. The FLURY-LEP C25 strain of rabies virus was adapted to propagate in primary chick embryo cell cultures. The antigen was purified and concentrated by continuous density gradient centrifugation and inactivated by Betapropiolactone. The PCEC-rabies vaccine was tested for innocuity, tolerability and protective capacity in a series of laboratory tests and compared with Human Diploid Cell Strain rabies vaccine (HDCSV) of similar antigenicity. The results of the laboratory tests indicated that this new vaccine was excellently tolerated and that its protective activity met the high standard of HDCS-vaccine, conditions which were imposed on the PCEC-vaccine before clinical trials in man were initiated.


A method for identification of diastereomers of 2-decarboxy-betacyanins and 2,17-bidecarboxy-betacyanins in reversed-phase HPLC.
A method was developed for identification of diastereomers of 2-decarboxy-betacyanins and 2,17-bidecarboxy-betacyanins chromatographed in reversed-phase high-performance liquid chromatography (HPLC) as pairs of unknown elution order. The method was based on alkaline hydrolysis of selected betacyanin and decarboxylated betacyanin mixtures and subsequent cross-recondensation of the hydrolysates. The arising intermediate derivatives of decarboxylated betalamic acid and cyclo-dopa were stable enough for subsequent recondensation. Generated diagnostic pigments as the recondensation products were monitored by HPLC-diode-array detection-electrospray ionisation mass spectrometry. The isoforms (15R) of 2-decarboxy-betacyanins and 2,17-bidecarboxy-betacyanins were eluted earlier than the 15S forms, in contrast to betacyanins and 17-decarboxy-betacyanins, but in accordance with betaxanthins. 2,17-Bidecarboxy-betanin/2,17-bidecarboxy-isobetanin, being not resolved in reversed-phase HPLC, were partially separated by ion-pair chromatography and under these conditions their order of elution was the same as that of acylated 2,17-bidecarboxy-betacyanins. The method allows complete identification of all the decarboxylated groups of betanin, phyllocactin and hylocerenin as well as other betacyanins in biological or pharmaceutical material.


Discrimination between Sporothrix schenckii and Ceratocystis stenoceras rhamnomannans by proton and carbon-13 magnetic resonance spectroscopy.
The proton and (13)C magnetic resonance (CMR) spectra of 10 Sporothrix schenckii and three Ceratocystis stenoceras rhamnomannans were studied. On the basis of their CMR spectra, the rhamnomannans from S. schenckii strains could be classified into two major types, I and II, readily distinguishable from the polysaccharides formed at the same temperature (25 C) by C. stenoceras. Rhamnomannans from S. schenckii synthesized at 37 C gave CMR spectra (type III) differing from those of polysaccharides of types I and II and from those of C. stenoceras polysaccharides. The contention that C. stenoceras might be the perfect form of S. schenckii is not supported by the present data. A presumptive pathogenic mutant of C. stenoceras synthesized a type I rhamnomannan characteristic of S. schenckii, clearly differing from the rhamnomannans from C. stenoceras synthesized in the same conditions. Nuclear magnetic resonance spectroscopy revealed differences in the structures of the polysaccharides from these species not previously recognized by methylation analysis.


Tardive dyskinesia in bipolar disorders: possible role of pineal melatonin.
Several clinical studies have suggested that patients with affective disorders, are at high risk for developing tardive dyskinesia (TD). An intriguing aspect of the relationship between TD and affective disorders involves mood dependent alterations in severity of TD. In most reported cases, depressive episodes are associated with exacerbation of TD, while manic episodes are accompanied by attenuation of TD. Current neurochemical hypotheses of TD do not explain adequately the relations of TD to depression or the mood dependent variations in the severity of TD. I propose that alterations in the secretory activity of pineal melatonin during manic and depressive episodes may explain better both the higher risk of TD in patients with affective disorders and the mood-dependent fluctuations in severity of TD. Consideration of pineal melatonin functions may further our understanding of the pathophysiology of TD in patients with affective disorders.


Impact of place of residence on relationship between quality of life and cognitive decline in dementia.
The aim of this descriptive study was to estimate and compare the association between cognitive decline and quality of life (QOL) for 2 groups of dementia patients differing by place of residence: home or institution. Each subject was placed within a specific subgroup according to their Mini-Mental State Examination (MMSE) score and was evaluated by a QOL proxy-assessment [Alzheimer Disease Related Quality of Life (ADRQL)] and a dependency assessment (Katz Activities of Daily Living classification). For the "at home" and "institution" groups, global and subscale ADRQL scores showed significant differences between the 5 MMSE subgroups. Place of residence and MMSE subgroups significantly affected global and subscale ADRQL scores. The MMSE 4 to 8, 9 to 13, and 14 to 18 subgroups had ADRQL global scores significantly better in the institution group than the at home group. In contrast, the MMSE 19 to 23 and 0 to 3 subgroups had similar ADRQL global scores in both places of residence. In conclusion, there is no direct relationship between cognitive decline and QOL, and QOL does not seem to be better at home compared with the institution.


Time geography: a model for psychiatric life charting?
Since many years, life charting has been used to describe the life course and life events of psychiatric patients. The aim of the present study was to describe and evaluate time geographic life charts of 11 former psychiatric patients in order to promote systematic descriptions of their life events over time. Information on all events which was gathered from the life charts was analysed by manifest content analysis and reduced to four categories: information received by asking only about moves, social capacity, predisposing life events and/or stressful as well as precipitating life events. Our findings showed that this kind of life charts offered a comprehensive and structured picture. They describe a detailed life situation from one time period to another, where geographical sites serve as anchors. The patients expressed satisfaction with this method of combining an interview with a time geographic life line.


[Clear-cell sarcoma of the kidney: the clinico-morphological, immunohistochemical and electron microscopic study of 22 cases].
22 cases of clear cell sarcoma of the kidney (CCSK) were studied, 15 of them ultrastructurally and 7--immunohistochemically. CCSK is a rare malignant tumour of children, predominantly males, with an involvement of one kidney and frequent multiple metastases to the bones. Typical, epithelioid-trabecular, hyalinizing, cystic and myxoid variants are distinguished at the light microscopic level. As vimentin was found in tumour cells in all cases, antibodies against vimentin and cytokeratin can be recommended for differential diagnosis between CCSK and Wilms tumour and rhabdoid tumour. Peculiar vascular pattern can be revealed by means of antibodies against factor VIII. Immunohistochemical properties (presence of vimentin) and electron microscopy allow suggesting histogenic relation of CCSK with pericytes.


Nitric oxide suppresses cilia activity in ctenophores.
Cilia are the major effectors in Ctenophores, but very little is known about their transmitter control and integration. Here, we present a simple protocol to monitor and quantify cilia activity in semi-intact preparations and provide evidence for polysynaptic control of cilia coordination in ctenophores. Next, we screen the effects of several classical bilaterian neurotransmitters (acetylcholine, dopamine, L-DOPA, serotonin, octopamine, histamine, gamma-aminobutyric acid (GABA), L-aspartate, L-glutamate, glycine), neuropeptides (FMRFamide), and nitric oxide (NO) on cilia beating in Pleurobrachia bachei and Bolinopsis infundibulum . Only NO inhibited cilia beating, whereas other tested transmitters were ineffective. These findings further suggest that ctenophore-specific neuropeptides could be major candidate signaling molecules controlling cilia activity in representatives of this early-branching metazoan lineage.


Alcohol-mediated haemolysis in yeast.
Although yeast are generally non-haemolytic, we have found that addition of alcohol vapour confers haemolytic properties on many strains of yeast and other fungi. We have called this phenomenon 'microbial alcohol-conferred haemolysis' (MACH). MACH is species- and strain-specific: whereas all six Candida tropicalis strains tested were haemolytic in the presence of ethanol, none among 10 C. glabrata strains tested exhibited this phenomenon. Among 27 C. albicans strains and 11 Saccharomyces cerevisiae strains tested, ethanol-mediated haemolysis was observed in 11 and 4 strains, respectively. Haemolysis is also dependent on the alcohol moiety: n-butanol and n-pentanol could also confer haemolysis, whereas methanol and 2-propanol did not. Haemolysis was found to be dependent on initial oxidation of the alcohol. Reduced haemolysis was observed in specific alcohol dehydrogenase mutants of both Aspergillus nidulans and S. cerevisiae. MACH was not observed during anaerobic growth, and was reduced in the presence of pararosaniline, an aldehyde scavenger. Results suggest that initial oxidation of the alcohol to the corresponding aldehyde is an essential step in the observed phenomenon.


Hemisphere division and its effect on selective attention: a generality examination of Lavie's load theory.
The present study examined the role of visual presentation mode (unilateral vs. bilateral visual fields) on attentional modulation. We examined whether or not the presentation mode affects the compatibility effect, using a paradigm involving two task-relevant letter arrays. Sixteen participants identified a target letter among task-relevant letters while ignoring either a compatible or incompatible distracter letter that was presented to both hemispheres. Two letters arrays were presented to visual fields, either unilaterally or bilaterally. Results indicated that the compatibility effect was greater in bilateral than in unilateral visual field conditions. Findings support the assumption that the two hemispheres have separate attentional resources.


Effect of different types and levels of fat addition and pellet binders on physical pellet quality of broiler feeds.
Two experiments were conducted to evaluate the effects of different types and levels of mixer-added fat (soybean oil: SO and calcium fat powder: CFP) and pellet binders (PBs: calcium lignosulfonate (CaLS) and bentonite (Ben)) on physical pellet quality (PPQ) parameters. PPQ included pellet durability index (PDI), pellet hardness, and pellet length of broiler diets processed under short-term conditioning. The first experiment had 4 treatments arranged as a 2 × 2 factorial with 2 types (SO and CFP) and 2 levels (1.5 and 3%) of mixer-added fat. In the second experiment, 22 treatments, combinations of 2 types of mixer-added fat (SO and CFP) at 3 levels (0, 1.5 and 3%) and 2 types of PB (CaLS = 0, 0.5, and 1% and Ben = 0, 1, and 2%), were arranged by a completely randomized design. PDI was measured by 2 devices: Pfost Tumbling box (PDIT) and Holmen NHP tester (PDIH). The results showed that the diets containing 1.5% CFP without PB had significant differences in all PPQ parameters. The results revealed that adding 0.5% CaLS to the 3% SO diets significantly enhanced PDIH, pellet hardness, and pellet length compared to other treatments. Moreover, 1.5% CFP diets with 2% Ben had significantly higher PDIT, PDIH, and pellet hardness among the treatments. Based on contour plots, different levels of Ben in the diets containing SO failed to create optimum PDIT values (>96%). However, 1.5 to 2.50% CFP diets without Ben had the optimum PDIT values. The optimum PDIT value was achieved by the diets containing 3% SO in the range of 0.21 to 0.56% CaLS. Furthermore, adding 0.5% CaLS to the diets containing less than 2.86% SO resulted in suboptimal PDIT values (<96%). The diets containing 1.5 to 2.50% CFP without CaLS had the optimum PDIT values. However, increasing CaLS levels more than 0.38% led to suboptimal PDIT values. Overall, these results indicated that the selection of appropriate PBs should be based on type and level of mixer-added fat.


Insulin-like peptide 5 fails to improve metabolism or body weight in obese mice.
Insulin-like peptide 5 (INSL5) is a member of the insulin-like family of peptides. It has been reported to be orexigenic in rodent models of obesity with impaired glucose metabolism. We attempted to confirm this property as a first step in establishing the ability of INSL5 to successfully integrate with other agents more proven in their ability to reverse obesity and improve metabolism. INSL5 was chemically synthesized by two alternative methods to a native form and one that was site-specifically conjugated to a 20 KDa polyethylene glycol (PEG) polymer. The pharmacology of each peptide was assessed by high-dose chronic administration in normal and obese mice. INSL5 failed to produce pharmacologically relevant effects on food intake, body weight or glucose control indicative of a negligible role of the peptide in the control of feeding and glucose metabolism.


Ten years of vegetation assembly after a North American mega fire.
Altered fuels and climate change are transforming fire regimes in many of Earth's biomes. Postfire reassembly of vegetation--paramount to C storage and biodiversity conservation--frequently remains unpredictable and complicated by rapid global change. Using a unique data set of pre and long-term postfire data, combined with long-term data from nearby unburned areas, we examined 10 years of understory vegetation assembly after the 2002 Hayman Fire. This fire was the largest wildfire in recorded history in Colorado, USA. Resistance (initial postfire deviance from prefire condition) and resilience (return to prefire condition) declined with increasing fire severity. However, via both resistance and resilience, 'legacy' species of the prefire community constituted >75% of total plant cover within 3 years even in severely burned areas. Perseverance of legacy species, coupled with new colonizers, created a persistent increase in community species richness and cover over prefire levels. This was driven by a first-year increase (maintained over time) in forbs with short life spans; a 2-3-year delayed surge in long-lived forbs; and a consistent increase in graminoids through the 10th postfire year. Burning increased exotic plant invasion relative to prefire and unburned areas, but burned communities always were >89% native. This study informs debate in the literature regarding whether these increasingly large fires are 'ecological catastrophes.' Landscape-scale severe burning was catastrophic from a tree overstory perspective, but from an understory perspective, burning promoted rich and productive native understories, despite the entire 10-year postfire period receiving below-average precipitation.


Synthesis and anti-HIV properties of new carbamate prodrugs of AZT.
A series of new 5'-O-carbamate prodrugs of AZT have been prepared. The stability in biological media, anti-HIV properties and pharmacokinetic parameters in dogs were evaluated. The compounds display moderate anti-HIV activity in cell culture. After oral administration of carbamate IV in dogs, both intact prodrug IV and released AZT were discovered in dog blood. Pharmacokinetic parameters of the compound IV were estimated. Half-life (T(1/2)) of AZT released after oral administration of IV in dogs was close to that after administration of AZT itself, and time to the maximum concentration (T(max)) of AZT released from IV was two and three times longer compared with that of AZT and H-phosphonate AZT, respectively. Acute toxicity was more than five times less if compared with AZT. As a result, we consider this series of carbamate derivatives of AZT as perspective for development of anti-HIV agents.


Cell generation dynamics underlying naive T-cell homeostasis in adult humans.
Thymic involution and proliferation of naive T cells both contribute to shaping the naive T-cell repertoire as humans age, but a clear understanding of the roles of each throughout a human life span has been difficult to determine. By measuring nuclear bomb test-derived 14C in genomic DNA, we determined the turnover rates of CD4+ and CD8+ naive T-cell populations and defined their dynamics in healthy individuals ranging from 20 to 65 years of age. We demonstrate that naive T-cell generation decreases with age because of a combination of declining peripheral division and thymic production during adulthood. Concomitant decline in T-cell loss compensates for decreased generation rates. We investigated putative mechanisms underlying age-related changes in homeostatic regulation of CD4+ naive T-cell turnover, using mass cytometry to profile candidate signaling pathways involved in T-cell activation and proliferation relative to CD31 expression, a marker of thymic proximity for the CD4+ naive T-cell population. We show that basal nuclear factor κB (NF-κB) phosphorylation positively correlated with CD31 expression and thus is decreased in peripherally expanded naive T-cell clones. Functionally, we found that NF-κB signaling was essential for naive T-cell proliferation to the homeostatic growth factor interleukin (IL)-7, and reduced NF-κB phosphorylation in CD4+CD31- naive T cells is linked to reduced homeostatic proliferation potential. Our results reveal an age-related decline in naive T-cell turnover as a putative regulator of naive T-cell diversity and identify a molecular pathway that restricts proliferation of peripherally expanded naive T-cell clones that accumulate with age.


Biomimetic alignment of zinc oxide nanoparticles along a peptide nanofiber.
Zinc oxide (ZnO) has potential applications in solar cells, chemical sensors, and piezoelectronic and optoelectronic devices due to its attractive physical and chemical properties. Recently, a solution-phase method has been used to synthesize ZnO crystals with diverse (from simple to hierarchical) nanostructures that is simple, of low cost, and scalable. This method requires template molecules to control the morphology of the ZnO crystals. In this paper, we describe the design and synthesis of two short peptides (RU-003,Ac-AIEKAXEIA-NH(2); RU-027, EAHVMHKVAPRPGGGAIEKAXEIA-NH(2); X = l-2-naphthylalanine) and the characterization of their self-assembled nanostructures. We also report their potential for ZnO mineralization and the alignment of ZnO nanoparticles along peptide nanostructures at room temperature. Interestingly, nonapeptide RU-003 predominantly formed a straight fibrous structure and induced the nucleation of ZnO at its surface, leading to an alignment of ZnO nanoparticles along a peptide nanofiber. This novel method holds promise for the room-temperature fabrication of ZnO catalysts with increased specific surface area, ZnO-gated transistors, and ZnO-based nanomaterials for optical applications.


Effects of dietary selenium and fish oil (MaxEPA) on arachidonic acid metabolism and hemostatic function in rats.
This study investigated whether hemostatic function can be modified by both the consumption of fish oil and the level of dietary selenium. Male Sprague-Dawley rats were fed for 8 wk semipurified diets containing 7% corn oil (by wt) or 5.5% fish oil (MaxEPA) plus 1.5% corn oil with or without selenium supplementation. Consumption of the four diets caused no difference in weight gain, food intake or plasma malondialdehyde content. The selenium-supplemented rats had significantly higher levels of selenium and glutathione peroxidase activity in plasma. Fish oil feeding decreased ADP-induced platelet aggregation and increased bleeding time. The level of dietary selenium and type of oil interacted to influence the production of 6-keto-prostaglandin F1 alpha: more was produced when corn oil was fed in the selenium-deficient diets. These data suggest that the effect of dietary selenium on hemostatic function and the production of eicosanoids is minor.


Fear, human shields and the redistribution of prey and predators in protected areas.
Protected areas form crucial baselines to judge ecological change, yet areas of Africa, Asia and North America that retain large carnivores are under intense economic and political pressures to accommodate massive human visitation and attendant infrastructure. An unintended consequence is the strong modulation of the three-way interaction involving people, predators and prey, a dynamic that questions the extent to which animal distributions and interactions are independent of subtle human influences. Here, I capitalize on the remarkable 9-day synchronicity in which 90% of moose neonates in the Yellowstone Ecosystem are born, to demonstrate a substantive change in how prey avoid predators; birth sites shift away from traffic-averse brown bears and towards paved roads. The decade-long modification was associated with carnivore recolonization, but neither mothers in bear-free areas nor non-parous females altered patterns of landscape use. These findings offer rigorous support that mammals use humans to shield against carnivores and raise the possibility that redistribution has occurred in other mammalian taxa due to human presence in ways we have yet to anticipate. To interpret ecologically functioning systems within parks, we must now also account for indirect anthropogenic effects on species distributions and behaviour.


Kinetic index combining native and postcontrast myocardial T1 in hypertrophic cardiomyopathy.
To evaluate ability of pre- and postcontrast apparent T1* indices, as well as their combination to characterize myocardial structural changes in hypertrophic cardiomyopathy (HCM). Study protocol was approved by institutional review board and informed consent was obtained. T1 mapping was performed using MOLLI sequence (1.5T magnet) on: (i) tubes with known T1 and varied heart-rates (HR), (ii) 17 HCM (55 ± 15 years) and 18 controls (49 ± 16 years), before contrast and every 5 min over 20 min postcontrast. Global and segmental native T1 (T1*Native ), extracellular volume (ECV) and percentage of decrease in myocardial T1* (T1*decay = 100·[1-T1*Post-contrast /T1*Native ]) were estimated. Correlation coefficients of associations between T1 and LV indices, such as left ventricular wall thickness (WT) and mass index (LVMi) were provided. Receiver operator curve analysis was performed on per-patient basis to assess ability of T1* indices to identify HCM. While up to a T1* of 1000 ms the effect of HR was minor, it was more pronounced above 1000 ms. T1*Native (754 ± 76 ms versus 1014 ± 130 ms, P < 0.001), ECV20min (23 ± 5% versus 27 ± 4%, P = 0.005), and T1*decay5, 10, 15 or 20min (38 ± 8% versus 54 ± 6%, P < 0.001) showed significant differences between controls and HCM. Correlation coefficients for associations with WT and LVMi were higher for T1*Native and T1decay, independent of acquisition time (with WT/LVMi: r = 0.58/0.44 (P < 0.05) for T1*Native ; r = 0.23 (P < 0.05)/0.23 for ECV20min ; r > 0.51/ > 0.45(P < 0.05) for T1*decay5, 20min ). T1*Native (97.1%) and T1*decay (91.2%) characterized HCM with higher accuracy (P < 0.02) than ECV (69%). T1*Native and T1*decay were able to characterize HCM more accurately than ECV, even in the absence of myocardial hypertrophy and late-gadolinium enhancement.


The Effect of the Addition of Hazelnut or Walnut Flour on the Rheological Characteristics of Wheat Dough.
The aim of this study was to evaluate the effect of the addition of hazelnut or walnut flour on the rheological properties of flour and wheat dough (WD). The research material was a system in which wheat flour was replaced with flour based on hazelnuts (HF) or walnuts (WF), i.e., nut flour, in the amounts of 5%, 10% and 15% (WDH, WDW). As a part of the research methodology, we analysed the wet gluten content, and farinographic and extensographic analyses of the dough were performed. Sweep frequency, creep and recovery tests were used to assess the viscoelastic properties of the tested doughs. It was found that the doughs with the addition of walnuts were characterized by different rheological properties compared to the control sample. The systems in which wheat flour was replaced with nuts were characterized by lower water absorption, and this parameter decreased as the share of nuts in the system increased. The mean value of this parameter for WDH was 48.6%, and in the case of WDW it was 47.9%. The development times of WDH and WDW doughs were longer compared to the control, but they decreased as the addition of nut flour was increased. The WDH doughs were characterized by the lowest stability and the highest degree of softening among the examined doughs. It was shown that the addition of nut flour reduced the values of the storage (G') and loss (G″) modules characterizing the tested doughs, while in each case the G' value was greater than the G″ value, which proves the advantage of the elastic properties. The creep and recovery tests showed that the nut dough was more susceptible to deformation compared to the control, which indicates that the presence of nut flour weakens the formation of the gluten network forming the dough structure, and makes it more susceptible to stress.


Interfacial behaviour of strontium-containing hydroxyapatite cement with cancellous and cortical bone.
The bone-bonding behaviors of various biomaterials have been extensively investigated. However, the precise mechanisms of bone bonding have not yet been clarified, and the differences in interfacial behaviors of biomaterial bonding with cancellous bone and cortical bone have not yet been understood. In this study, strontium-containing hydroxyapatite (Sr-HA) cement, in which 10% calcium ions were substituted by strontium, was performed in a rabbit hip replacement model. Six months later, the morphology and chemical composition of interfaces between Sr-HA cement with cancellous bone and cortical bone were evaluated by field emission scanning electron microscopy (FESEM) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). Remarkable differences between these two interfaces were suggested both in morphology and chemical compositions. An apatite layer was found between Sr-HA cement and cancellous bone with a thickness of about 70 microm. However, only a very thin interface (about 1 microm) was formed with cortical bone. As for the cancellous bone/cement interface, high ions intensity of Ca, P, Sr, Na, and O were confirmed by FESEM-EDX and ToF-SIMS. Differences in morphology and chemical component between these two interfaces provided convincing evidences for the proposed dissolution-precipitation coupling mechanism in the formation of biological apatite.


Altered Glucosinolate Profiles and Expression of Glucosinolate Biosynthesis Genes in Ringspot-Resistant and Susceptible Cabbage Lines.
Ringspot, caused by the fungus Mycosphaerella brassicicola, is a serious disease of Brassica crops worldwide. Despite noteworthy progress to reveal the role of glucosinolates in pathogen defense, the host⁻pathogen interaction between cabbage (Brassica oleracea) and M. brassicicola has not been fully explored. Here, we investigated the glucosinolate profiles and expression of glucosinolate biosynthesis genes in the ringspot-resistant (R) and susceptible (S) lines of cabbage after infection with M. brassicicola. The concomitant rise of aliphatic glucoiberverin (GIV) and indolic glucobrassicin (GBS) and methoxyglucobrassicin (MGBS) was linked with ringspot resistance in cabbage. Pearson's correlation and principle component analysis showed a significant positive association between GIV contents and the expression of the glucosinolate biosynthesis gene ST5b-Bol026202 and between GBS contents and the expression of the glucosinolate biosynthesis gene MYB34-Bol017062. Our results confirmed that M. brassicicola infection induces the expression of glucosinolate biosynthesis genes in cabbage, which alters the content of individual glucosinolates. This link between the expression of glucosinolate biosynthesis genes and the accumulation of their respective glucosinolates with the resistance to ringspot extends our molecular sense of glucosinolate-negotiated defense against M. brassicicola in cabbage.


Long-Term Survival after Microfracture and Mosaicplasty for Knee Articular Cartilage Repair: A Comparative Study Between Two Treatments Cohorts.
To investigate survival of cartilage repair in the knee by microfracture (MFX; n = 119) or mosaicplasty osteochondral autograft transfer (OAT; n = 84). For survival analyses, "failure" was defined as the event of a patient reporting a Lysholm score <65 or undergoing an ipsilateral knee replacement. The Kaplan-Meier method was used for construction of a survival functions plot for the event "failure." Log rank (Mantel-Cox) test was used for comparison of survival distributions in the 2 groups. The long-term failure rate (62% overall) was significantly higher in the MFX group (66%) compared with the OAT group (51%, P = 0.01). Furthermore, the mean time to failure was significantly shorter (P < 0.001) in the MFX group, 4.0 years (SD 4.1) compared with the OAT group, 8.4 years (SD 4.8). In the OAT group, the survival rate stayed higher than 80% for the first 7 years, and higher than 60% for 15 years, while the survival rate dropped to less than 80% within 12 months, and to less than 60% within 3 years in the MFX group, log rank (Mantel-Cox) 20.295 (P < 0.001). The same pattern was found in a subgroup of patients (n = 134) of same age (<51 years) and size of treated lesion (<500 mm2), log rank (Mantel-Cox) 10.738 (P = 0.001). The nonfailures (48%) were followed for median 15 yeas (1-18 years). MFX articular cartilage repairs failed more often and earlier than the OAT repairs, both in the whole cohort and in a subgroup of patients matched for age and size of treated lesion, indicating that the OAT repair is the more durable. Therapeutic study, Level III.


Development of leading indicators for the assessment of occupational health performance using Reason's Swiss cheese model.
The Swiss cheese model of accident causation is a model used in risk analysis and risk management, including aviation safety, engineering, healthcare, and emergency service organizations, and as the principle behind layered security, as used in computer security and defense in-depth. This study aimed to develop and weight the occupational health leading indicators using the Swiss cheese model. The present study was a descriptive, cross-sectional study; occupational health performance assessment indicators were classified into five main groups of chemical, physical, ergonomic, psychosocial, and biological harmful agents. In addition, potential hazards and their prevention methods were identified using the Swiss cheese model. The leading performance measurement indicators (n = 64) were developed based on preventive methods and were weighted and rated by fuzzy analytic hierarchy process. Thirty-six out of 64 indicators were related to the management measures, 25 indicators were related to exposure to harmful occupational agents, and the remaining indicators were occupational-related illnesses and diseases rate. Considering the importance and frequency of indicators, psychological agents were the most important indicators (40%) and physical agents had the greatest frequency (59%). Process of indicators' development has demonstrated that the major occupational health prevention measures in the oil and gas industry are concentrated on physical, psychological, and chemical agents, respectively. Thus, to provide protection for employees against occupational diseases and improve health performance indicators, paying special attention to mentioned agents is essential in the oil and gas industry.


Posterior tibial neuropathy by a Baker's cyst: case report.
Baker's cysts are rare cause of peripheral nerve entrapment and only a few cases of tibial nerve entrapment resulting from the popliteal cyst in the calf muscle have been reported in the literature. We present a case of rheumatoid arthritis complicated by a Baker's cyst with a tibial nerve entrapment. It is important to diagnose a Baker's cyst early and to differentiate it from thrombophlebitis, a popliteal aneurysm, tumor or muscle tear to effect optimal therapy and to obviate a potential neuropathy. Prompt recognition of these cases may save the patients unnecessary procedures and delay in treatment.


Dapagliflozin-induced weight loss affects 24-week glycated haemoglobin and blood pressure levels.
The aim of this study was to investigate the associations between dapagliflozin-mediated reductions in body weight and reductions in glycated haemoglobin (HbA1c) and blood pressure. Data were pooled from seven studies evaluating dapagliflozin 10 mg as monotherapy or combination therapy over 24 weeks. Using linear regression to estimate the contribution of weight loss to HbA1c and blood pressure reductions, the β-value estimate for HbA1c (%)/kg was 0.028 (p < 0.0001). Weight loss of 2 kg with dapagliflozin contributed to 6% of the total HbA1c reduction. For systolic (SBP) and diastolic blood pressure (DBP), the β-value (mmHg/kg) estimates were 0.606 (p < 0.0001) and 0.253 (p < 0.0001), respectively. Weight loss of 2 kg contributed to 28% of the overall SBP reduction, and 24% of the overall DBP reduction. In conclusion, dapagliflozin-mediated weight loss may contribute to overall reductions in HbA1c and blood pressure.


Diuretic and vasodilating actions of torasemide.
The pharmacological profile of torasemide was examined in experimental animals. In normotensive Wistar rats, torasemide produced less kaliuresis at doses that were equipotent with furosemide in terms of natriuresis. Torasemide but not furosemide exerted a significant diuretic action in rats treated with deoxycorticosterone acetate. Both torasemide and furosemide increased plasma renin activity and aldosterone concentration, but only torasemide significantly inhibited aldosterone-receptor binding in rat kidney. Torasemide also inhibited vasoconstriction induced by thromboxane A2 in isolated canine coronary artery.


Energy repartition for a harmonic chain with local reservoirs.
We exactly analyze the vibrational properties of a chain of harmonic oscillators in contact with local Langevin heat baths. Nonequilibrium steady-state fluctuations are found to be described by a set of mode temperatures, independent of the strengths of both the harmonic interaction and the viscous damping. Energy is equally distributed between the conjugate variables of a given mode but differently among different modes, in a manner which depends exclusively on the bath temperatures and on the boundary conditions. We outline how bath-temperature profiles can be designed to enhance or reduce fluctuations at specific frequencies in the power spectrum of the chain length.


Sandfly fauna (Diptera: Psychodidae) in an urban area, Central-West of Brazil.
Biological and ecological relations among vectors and their pathogens are important to understand the epidemiology of vector-borne diseases. Camapuã is an endemic area for visceral and tegumentary leishmaniasis. The aim of this study was to characterize the sandfly fauna present in Camapuã , MS, Brazil. Sand flies were collected every fortnight from May 2014 to April 2015 using automatic light traps in the domicile and peridomicile of twelve neighborhoods and forest. The collected specimens were identified based on morphology according to the valid identification keys. In total, 2005 sandflies of five genera and nine species were collected. Nyssomyia whitmani and Lutzomyia cruzi were the most abundant species. Males were more abundant, with a male-to-female ratio of 2.14. The highest diversity was observed in peripheral neighborhood, with abundant plant cover. The peridomicile presented greater abundance of sandflies, with the predominance of Ny. whitmani . No significant correlation between the absolute frequencies of the most abundant species and the precipitation variable was observed; however, there was a predominance of Lu. cruzi in the rainy season. We observed a high frequency of sandflies in urban area, especially vector species. The presence of Nyssomyia whitmani and Lutzomyia cruzi indicate the necessity for health surveillance in the municipality. Additional method of collection such as sticky trap is also recommended for appropriate faunestic study.


Intracellular and extracellular enzymatic deacylation of bacterial endotoxin during localized inflammation induced by Escherichia coli.
Acyloxyacyl hydrolase (AOAH), an enzyme that removes the secondary acyl chains of gram-negative bacterial lipid A (endotoxin), has been identified previously in human neutrophils and mouse macrophages. We report here that bovine leukocytes also contain AOAH activity. Although bovine AOAH deacylates bacterial lipopolysaccharide in a manner similar to human AOAH, it is active in vitro over a broader pH range, from 4.0 to 7.0. By using Escherichia coli infection of the bovine mammary gland as a model of localized gram-negative bacterial disease and associated tissue inflammation, AOAH activity per leukocyte increased. In addition, AOAH activity increased in the cell-free portion of infected mammary secretions. These data indicate that AOAH activity increases in leukocytes associated with inflammation induced by gram-negative bacteria and provide additional evidence of its potential involvement in the defense against the effects of bacterial endotoxin.


Lubricity of Ethanol-Diesel Fuel Blends-Study with the Four-Ball Machine Method.
Due to the increasing consumption of fuels in heavy industries, especially in road transportation, significant efforts are being made to increase the market participation of renewable fuels, including ethanol. In diesel engines, however, ethanol cannot be used as a pure fuel, primarily due to its very low cetane number and lubricity. For this reason, greater attention is being paid to blended fuels containing diesel and varying percentages of ethanol. Tests of lubricating properties carried out in accordance with the standard HFRR (high frequency reciprocating rig) method for ethanol-diesel fuel blends have long durations, which leads to ethanol evaporation and changes in the composition of the tested fuel sample under elevated temperatures. Therefore, this study presents an alternative lubricity assessment criterion based on the measurement of the scuffing load with a four-ball machine. Lubricity tests of blends of typical diesel fuel and ethanol, with ethanol volume fractions up to 14% (v/v), were conducted using a four-ball machine with a continuous increase of the load force of the friction node. In this method the lubrication criterion was the scuffing load of the tribosystem. The obtained results provided insights into the influence of the addition of ethanol to diesel fuel on lubricating properties, while limiting the ethanol evaporation process. The results also showed that an increase in the fraction of ethanol up to 14% (v/v) in diesel fuel resulted in a decrease in the scuffing load and a corresponding deterioration in the lubricating properties of the diesel-ethanol blend. For an ethanol volume fraction of 6-14%, the changes in the scuffing load were smaller than in ethanol volume fractions of 0-6%.


Relationship between periodontal outcomes and serum biomarkers changes after non-surgical periodontal therapy.
The systemic effect of chronic periodontitis (CP) has been suggested by several studies as an etiologic factor and modulator of diseases based on the changes in the inflammatory marker levels. This study aimed to investigate the relationship between the changes in clinical periodontal outcomes and serum biomarkers (CRP, IL-6, albumin and percentage of leukocytes) after non-surgical periodontal therapy in systemically healthy adults. An interventional study was conducted with a sample of 29 individuals without CP (control group) and 33 with CP (CP group). Periodontal clinical variables were recorded, and the serum levels of inflammatory markers were measured. Statistical analysis included the chi-square and Student's t-tests and Pearson's correlation analysis. After 90 days of non-surgical periodontal treatment, a reduction of periodontal parameters and IL-6 in both groups could be observed (P < 0.001). The correlation analysis revealed a directly proportional correlation between changes in the probing depth (r = 0.349, P = 0.049) and clinical attachment level (r = 0.374, P = 0.034) with CRP in the CP group. The findings suggest a reduction of IL-6 serum concentration and periodontal clinical measures 90 days after periodontal therapy in both groups.


SMN-assisted assembly of snRNP-specific Sm cores in trypanosomes.
Spliceosomal small nuclear ribonucleoproteins (snRNPs) in trypanosomes contain either the canonical heptameric Sm ring (U1, U5, spliced leader snRNPs), or variant Sm cores with snRNA-specific Sm subunits (U2, U4 snRNPs). Searching for specificity factors, we identified SMN and Gemin2 proteins that are highly divergent from known orthologs. SMN is splicing-essential in trypanosomes and nuclear-localized, suggesting that Sm core assembly in trypanosomes is nuclear. We demonstrate in vitro that SMN is sufficient to confer specificity of canonical Sm core assembly and to discriminate against binding to nonspecific RNA and to U2 and U4 snRNAs. SMN interacts transiently with the SmD3B subcomplex, contacting specifically SmB. SMN remains associated throughout the assembly of the Sm heteroheptamer and dissociates only when a functional Sm site is incorporated. These data establish a novel role of SMN, mediating snRNP specificity in Sm core assembly, and yield new biochemical insight into the mechanism of SMN activity.


Re-evaluation of the diagnostic utility of serum total creatine kinase and creatine kinase-2 in myocardial infarction.
The diagnostic utility of total creatine kinase activity (I), creatine kinase-2 isoenzyme activity (II), and II as a percentage of I, was examined by receiver-operating characteristic curve and likelihood ratio (LR) analyses in 310 persons admitted to the Coronary Care Unit (151 proven cases of myocardial infarction and 159 non-myocardial infarction controls), from whom blood was sampled at 6-h intervals for 48 h after the onset of chest pain. I was ineffective either as a "rule-in" or as a "rule-out" test within the first 6 h of the onset of chest pain; thereafter, it was an effective test. II was the most effective test during the entire 48-h period. III was more effective than I in the first 24-h period, but was less effective than I during the next 24-h period. The decision threshold for high test sensitivities varies with time over the entire 48-h period, but remains constant for high test specificities. It is essential to tabulate the LR(+) and LR(-) values for both test sensitivity and specificity at constant values to determine the utility of each test at each time interval for respectively ruling out or ruling in a diagnosis of myocardial infarction.


The Status of Adolescent Testing and Treatment in PEPFAR-Supported Programs, October 2017 to September 2020.
Adolescents have poorer outcomes across the HIV cascade compared with adults. We aimed to assess progress in HIV case finding, antiretroviral treatment (ART), viral load coverage (VLC), and viral load suppression (VLS) among adolescents enrolled in the US President's Emergency Plan for AIDS Relief (PEPFAR)-supported programs over a 3-year period that included the beginning of the COVID-19 pandemic. We analyzed PEPFAR program data in 28 countries/regions for adolescents aged 10-19 years between year 1 (October 2017to September 2018), year 2 (October 2018 to September 2019), and year 3 (October 2019 to September 2020). We calculated the number and percent change for HIV tests, HIV-positive tests, and total number on ART. Calculated indicators included positivity, percent of positives newly initiated on ART (ART linkage), VLC (percent of ART patients on ART for ≥6 months with a documented viral load result within the past 12 months), and VLS (percent of viral load tests with <1000 copies/mL). Between years 1 and 3, the number of HIV tests conducted decreased by 44.2%, with a 29.1% decrease in the number of positive tests. Positivity increased from 1.3%-1.6%. The number of adolescents receiving ART increased by 10.4%. In addition, ART linkage increased (77.8%-86.7%) as did VLC (69.4%-79.4%) and VLS (72.8%-81.5%). Our findings demonstrate PEPFAR's success in increasing the adolescent treatment cohort. We identified ongoing gaps in adolescent case finding, linkage, VLC, and VLS that could be addressed with a strategic mix of testing strategies, optimal ART regimens, and adolescent-focused service delivery models.


The effect of facial expression and gaze direction on memory for unfamiliar faces.
We report data from an experiment that investigated the influence of gaze direction and facial expression on face memory. Participants were shown a set of unfamiliar faces with either happy or angry facial expressions, which were either gazing straight ahead or had their gaze averted to one side. Memory for faces that were initially shown with angry expressions was found to be poorer when these faces had averted as opposed to direct gaze, whereas memory for individuals shown with happy faces was unaffected by gaze direction. We suggest that memory for another individual's face partly depends on an evaluation of the behavioural intention of that individual.


An examination of economic outcomes associated with misdiagnosis or undertreatment of TIA.
Transient ischemic attack (TIA) is a common cerebrovascular event that is associated with a high risk for secondary stroke, possibly higher than stroke itself. Nevertheless, a TIA is often described as a "mini-stroke," implying a less serious event requiring less urgent treatment. In reality, TIA and subsequent secondary stroke are associated with a very high economic burden. Cerebrovascular disease is the most financially costly of all major disease states, while morbidity and mortality risk is highly elevated in TIA patients. TIA is also associated with a very severe quality-of-life burden, which manifests both in terms of diminished functional independence and high rates of depression. Furthermore, TIA is commonly misdiagnosed and underdiagnosed, often leading to inappropriate treatment. More than half of patients who experience TIA are undiagnosed, while those who do receive a diagnosis are often offered neither diagnostic imaging nor hospital admission. Much of the morbidity and mortality associated with TIA and secondary stroke might be avoided by the application of timely and appropriate treatment. Clinical data have shown that accelerated treatment of TIA during its acute phase is associated with an 80% reduction of secondary stroke risk for the following 3 months, the period of greatest risk.


Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis in 2 patients with end-stage renal disease on hemodialysis.
Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis (NFD/NSF) is a newly recognized disorder occurring in patients with renal failure. It is manifested by progressive cutaneous and systemic fibrosis involving the extremities and the trunk with usual sparing of the face and internal organs. NFD/NSF can lead to joint contractures and painful disability. The etiology is unknown and there are no proven effective treatments. NFD/NSF must be distinguished from other clinically similar disorders such as scleroderma, scleromyxedema, and eosinophilic fasciitis among a myriad of others. NFD/NSF can pose many diagnostic challenges to physicians; however, a team of experienced rheumatologists, nephrologists, dermatologists, and dermatopathologists is essential in identifying this disorder. We report 2 new cases of NFD/NSF in patients on hemodialysis.