COMPENSATORY BRAIN CONNECTION DISCOVERY IN ALZHEIMER'S DISEASE.
Identification of the specific brain networks that are vulnerable or resilient in neurodegenerative diseases can help to better understand the disease effects and derive new connectomic imaging biomarkers. In this work, we use brain connectivity to find pairs of structural connections that are negatively correlated with each other across Alzheimer's disease (AD) and healthy populations. Such anti-correlated brain connections can be informative for identification of compensatory neuronal pathways and the mechanism of brain networks' resilience to AD. We find significantly anti-correlated connections in a public diffusion-MRI database, and then validate the results on other databases.


Medical countermeasure against respiratory toxicity and acute lung injury following inhalation exposure to chemical warfare nerve agent VX.
To develop therapeutics against lung injury and respiratory toxicity following nerve agent VX exposure, we evaluated the protective efficacy of a number of potential pulmonary therapeutics. Guinea pigs were exposed to 27.03 mg/m(3) of VX or saline using a microinstillation inhalation exposure technique for 4 min and then the toxicity was assessed. Exposure to this dose of VX resulted in a 24-h survival rate of 52%. There was a significant increase in bronchoalveolar lavage (BAL) protein, total cell number, and cell death. Surprisingly, direct pulmonary treatment with surfactant, liquivent, N-acetylcysteine, dexamethasone, or anti-sense syk oligonucleotides 2 min post-exposure did not significantly increase the survival rate of VX-exposed guinea pigs. Further blocking the nostrils, airway, and bronchioles, VX-induced viscous mucous secretions were exacerbated by these aerosolized treatments. To overcome these events, we developed a strategy to protect the animals by treatment with atropine. Atropine inhibits muscarinic stimulation and markedly reduces the copious airway secretion following nerve agent exposure. Indeed, post-exposure treatment with atropine methyl bromide, which does not cross the blood-brain barrier, resulted in 100% survival of VX-exposed animals. Bronchoalveolar lavage from VX-exposed and atropine-treated animals exhibited lower protein levels, cell number, and cell death compared to VX-exposed controls, indicating less lung injury. When pulmonary therapeutics were combined with atropine, significant protection to VX-exposure was observed. These results indicate that combinations of pulmonary therapeutics with atropine or drugs that inhibit mucous secretion are important for the treatment of respiratory toxicity and lung injury following VX exposure.


Evaluation of three synthetic pyrethroids in the control of sheep headfly disease.
Deltamethrin (0.01 per cent) applied to the heads of lambs and gimmers at 30 day intervals on two separate farms failed to control damage caused by the sheep headfly , Hydrotaea irritans. Permethrin (0.1 per cent) applied to gimmers at monthly intervals achieved a slight reduction in severity of damage but protection did not extend beyond 14 days. Polyvinyl chloride tags containing 8.5 per cent cypermethrin reduced damage in gimmers to a very low level with protection lasting throughout the summer. Weight gains of lambs suffering headfly damage were significantly less than unaffected lambs.


In vitro biomechanical comparison of an anterior and anterolateral lumbar plate with posterior fixation following single-level anterior lumbar interbody fusion.
Anterior lumbar interbody fusion (ALIF) is often supplemented with instrumentation to increase stability in the spine. If anterior plate fixation provided the same stability as posterior pedicle screw fixation (PSF), then a second approach and its associated morbidity could be avoided. Seven human cadaveric L4-5 spinal segments were tested under three conditions: ALIF with an anterior plate, ALIF with an anterolateral plate, and ALIF supplemented by PSF. Range of motion (ROM) was calculated for flexion/extension, lateral bending, and axial torsion and compared among the three configurations. There were no significant differences in ROM during flexion/extension, lateral bending, or axial torsion among any of the three instrumentation configurations. The addition of an anterior plate or posterior PS/rod instrumentation following ALIF provides substantially equivalent biomechanical stability. Additionally, the position of the plate system, either anterior or anterolateral, does not significantly affect the stability gained.


Internode Length Is Correlated with GA3 Content and Is Crucial to the Harvesting Performance of Tea-Picking Machines.
High labor costs and labor shortages are limiting factors affecting the tea industry in Anhui Province. Thus, exploiting the full mechanization of shoot harvesting is an urgent task in the tea industry. Tea quality is greatly influenced by the integrity rate of tea leaves; therefore, it is important to choose tea cultivars suitable for machine picking. In this study, seven tea cultivars were used to investigate the relationship between internode length and blade angle with respect to newly formed tea shoots and machine harvesting in field experiments (Xuanchen City, Kuiling village) conducted throughout the year (in the autumn of 2021, in the early spring of 2022, and in the summer of 2022). Our results showed that the internode length (L2 or L4) had a significant and positive correlation with the integrity rate of tea buds and leaves in seven tea cultivars over three seasons. However, no significant correlation was found between the blade angle and the integrity rate of tea buds and leaves. In addition, a strong and positive correlation was found between the levels of GA1 (R2 > 0.7), GA3 (R2 > 0.85), and IAA (R2 > 0.6) regarding the internodes and internode lengths of the seven tea cultivars. Moreover, the relative expression levels of CsGA20ox, CsGA3ox1, and CsGA3ox2 in Echa1 (the longer internode) were significantly higher compared with those in Zhenong113 (the shorter internode). Overall, our results show that the internode length is an important factor for the machine harvesting of tea leaves and that the level of GA3 is strongly associated with internode length.


Decline in relative abundance of bottlenose dolphins exposed to long-term disturbance.
Studies evaluating effects of human activity on wildlife typically emphasize short-term behavioral responses from which it is difficult to infer biological significance or formulate plans to mitigate harmful impacts. Based on decades of detailed behavioral records, we evaluated long-term impacts of vessel activity on bottlenose dolphins (Tursiops sp.) in Shark Bay, Australia. We compared dolphin abundance within adjacent 36-km2 tourism and control sites, over three consecutive 4.5-year periods wherein research activity was relatively constant but tourism levels increased from zero, to one, to two dolphin-watching operators. A nonlinear logistic model demonstrated that there was no difference in dolphin abundance between periods with no tourism and periods in which one operator offered tours. As the number of tour operators increased to two, there was a significant average decline in dolphin abundance (14.9%; 95% CI=-20.8 to -8.23), approximating a decline of one per seven individuals. Concurrently, within the control site, the average increase in dolphin abundance was not significant (8.5%; 95% CI=-4.0 to +16.7). Given the substantially greater presence and proximity of tour vessels to dolphins relative to research vessels, tour-vessel activity contributed more to declining dolphin numbers within the tourism site than research vessels. Although this trend may not jeopardize the large, genetically diverse dolphin population of Shark Bay, the decline is unlikely to be sustainable for local dolphin tourism. A similar decline would be devastating for small, closed, resident, or endangered cetacean populations. The substantial effect of tour vessels on dolphin abundance in a region of low-level tourism calls into question the presumption that dolphin-watching tourism is benign.


RF-SOI Low-Noise Amplifier Using RC Feedback and Series Inductive-Peaking Techniques for 5G New Radio Application.
This paper presents a low-noise amplifier (LNA) with an integrated input and output matching network designed using RF-SOI technology. This LNA was designed with a resistive feedback topology and an inductive peaking technology to provide 600 MHz of bandwidth in the N79 band (4.4 GHz to 5.0 GHz). Generally, the resistive feedback structure used in broadband applications allows the input and output impedance to be made to satisfy the broadband conditions through low-impedance feedback. However, feedback impedance for excessive broadband characteristics can degrade the noise performance as a consequence. To achieve a better noise performance for a bandwidth of 600 MHz, the paper provided an optimized noise performance by selecting the feedback resistor value optimized for the N79 band. Additionally, an inductive peaking technique was applied to the designed low-noise amplifier to achieve a better optimized output matching network. The designed low-noise amplifier simulated a gain of 20.68 dB and 19.94 dB from 4.4 to 5.0 GHz, with noise figures of 1.57 dB and 1.73 dB, respectively. The input and output matching networks were also integrated, and the power consumption was designed to be 9.95 mA at a supply voltage of 1.2 V.


Herpes simplex virus type 2 suppressive therapy with acyclovir or valacyclovir does not select for specific HIV-1 resistance in HIV-1/HSV-2 dually infected persons.
Recent in vitro studies suggest that acyclovir may directly inhibit HIV-1 replication and can select for a specific HIV-1 reverse transcriptase mutation (V75I) with concomitant loss of an anti-HIV-1 effect. We tested for HIV-1 genotypic resistance at reverse transcriptase codon 75 in plasma from 168 HIV-1-infected persons from Botswana, Kenya, Peru, and the United States taking daily acyclovir or valacyclovir for between 8 weeks and 24 months. No V75I cases were detected (95% confidence interval, 0%-2.2%). These prospective in vivo studies suggest that standard-dose acyclovir or valacyclovir does not select for HIV-1 resistance.


Chemoarchitecture of the middle temporal visual area in the marmoset monkey (Callithrix jacchus): laminar distribution of calcium-binding proteins (calbindin, parvalbumin) and nonphosphorylated neurofilament.
We studied the distributions of interneurons containing the calcium-binding proteins parvalbumin and calbindin D-28k, as well as that of pyramidal neurons containing nonphosphorylated neurofilament (NNF), in the middle temporal visual area (MT) of marmoset monkeys. The distributions of these classes of cells in MT are distinct from those found in adjacent areas. Similar to the primary visual area (V1), in MT, calbindin-immunopositive neurons can be objectively classified into "dark" and "light" subtypes based on optical density of stained cell bodies. Calbindin-positive dark neurons are particularly concentrated in layers 2 and 3, whereas light neurons have a more widespread distribution. In addition, a subcategory of calbindin-positive dark neuron, characterized by a "halo" of stained processes surrounding the cell body, is found within and around layer 4 of MT and V1. These cells are rare in most other visual areas. In comparison, parvalbumin-immunopositive cells in area MT have a relatively homogeneous distribution, although with a trend toward higher spatial density in lower layer 3, and are relatively uniform in terms of density of staining. Finally, MT shows a characteristic trilaminar distribution of NNF-immunopositive pyramidal cells, with stained cell bodies evident in layers 3, 5, and 6. Although the laminar distribution of cells stained for the three markers overlap to some extent, these subcategories can be readily distinguished in terms of morphology, including cell body size. Chemoarchitectural parallels observed between MT and V1 suggest comparable physiological requirements and neuronal circuitry.


The Use of Selective Laser Melting to Increase the Performance of AlSi₉Cu₃Fe Alloy.
For the first time, the comprehensive characterization of the additively manufactured AlSi₉Cu₃Fe alloy is reported in this paper. Conventionally, the AlSi₉Cu₃(Fe) alloy is prepared by high-pressure die casting (HPDC), but this technology largely does not offer such opportunities as additive manufacturing (AM) does, especially in the design of new lightweight parts. In the present paper, testing samples were prepared by selective laser melting (SLM), one of the AM technologies, and characterized in terms of their microstructure (by means of light microscopy, scanning electron microscopy and transmission electron microscopy in combination with analytical techniques for evaluation of chemical and phase composition) and mechanical properties (static tension, compression, and hardness). All the characteristics were compared with the HPDC reference material. Our study showed an excellent improvement both in strength (374 ± 11 MPa compared to 257 ± 17 MPa) and plasticity (1.9 ± 0.2% compared to 1.2 ± 0.5%) of the material thanks to its very fine and distinctive microstructure.


The role of liver transplantation in the subacute trauma patients.
Two case reports are presented involving complex liver traumas requiring the need for liver transplantation. Both of these patients were designated unsalvageable until the transplant team was consulted. It is imperative that surgeons involved with complex hepatic trauma not give up hope and include these patients as potential liver recipients when irreversible liver failure occurs.


Whose diet has changed?
The same questions about diet were asked in two community-based surveys conducted in the Hunter Region of New South Wales in 1983 and 1994. There were substantial changes in diet over the period; for example, the proportion of respondents who reported using low-fat or skim milk increased from 25 per cent to 51 per cent, the proportion eating meat fewer than five times a week doubled from 21 per cent to 42 per cent and the proportion eating fewer than three eggs per week increased from 55 per cent to 80 per cent. In both surveys, women reported eating a healthier diet than men, and older people and those of higher socioeconomic status reported better diets than younger people or people with less education or lower status occupations. The surprising finding was that over the 11-year period the changes in patterns of food consumption were remarkably similar across all strata of the population. The conclusions are that wide-spread dietary change is possible. However, the changes in the last decade related mainly to reducing the risk of cardiovascular disease; similar behavioural changes to reduce the risk of diet-related cancer are required.


Expression of the heterologous Dunaliella tertiolecta fatty acyl-ACP thioesterase leads to increased lipid production in Chlamydomonas reinhardtii.
Biofuel production from genetically-engineered microalgae is currently among the most widely studied strategies in generating renewable energy. However, microalgae currently suffer from low oil yields which limit the commercial feasibility of industrial-scale production. A major bottleneck in cost-efficient biofuel production from microalgae is the dilemma between biomass productivity and lipid accumulation. When grown under stressful culture conditions such as nitrogen depletion, microalgae accumulate large amounts of neutral lipids, but it comes at the expense of growth which negatively impacts overall lipid productivity. Overexpression of acyl-ACP thioesterases (TE) had been successful in increasing the production of fatty acids (FA) in prokaryotes such as E. coli and cyanobacteria, but has not been effectively tested in microalgae. In this study, we introduced a TE from D. tertiolecta (DtTE) into C. reinhardtii to investigate its effects on FA production without compromising growth. The results indicate that C. reinhardtii transformants were able to produce 63 and 94% more neutral lipids than the wild-type, which translates to an approximately 56% improvement in total lipids, without compromising growth. These findings demonstrate the cross-species functionality of TE, and provide a platform for further studies into using TE as a strategy to increase biofuel production from microalgae.


Silicon chemistry in zero to three dimensions: from dichlorosilylene to silafullerane.
Silylenes and silanides, prominent Si(ii) species, are not only interesting in their own right, but also constitute important building blocks in oligosilane and organosilane chemistry. The past decade has witnessed tremendous advances in the understanding of the ambiphilic behavior of silylenes and the nucleophilic properties of silanides, as well as the mutual relationships between both species. Especially the readily available SiCl2/[SiCl3]- system is intriguing, because it features highly functionalized silicon centers, amenable to late-stage modifications. Moreover, SiCl2 and [SiCl3]- are interconvertible by mere chloride association/dissociation. This Feature Article first provides a brief introduction to isolable (functionalized) silylenes and silanides and then focusses on the SiCl2/[SiCl3]- couple. Classical high-temperature protocols for the generation of SiCl2 are juxtaposed with convenient recent solution phase methods that provide access to R3N-SiCl2 and [SiCl3]-via deprotonation of HSiCl3 or the amine-/chloride-induced disproportionation of Si2Cl6. We give a comprehensive overview of key mechanistic issues and highlight the utility of R3N-SiCl2 and [SiCl3]- for the synthesis of open-chain and cyclic oligosilanes as well as nanoscale, fullerene-type silicon clusters.


Thoracoscopic resection of unusual symptomatic pericardial cysts.
Pericardial cysts are mediastinal tumors that usually have a benign course. Diagnostic and therapeutic thoracoscopy are warranted for suspect mediastinal masses, unsuccessful nondiagnostic less invasive procedures, and symptomatic unusually located pericardial cysts. We report a case of thoracoscopic resection of symptomatic pericardial cysts.


A versatile approach to fabricate ordered heterogeneous bull's-eye-like microstructure arrays.
In this paper, ordered heterogeneous bull's-eye-like microstructure arrays were fabricated through a simple two-step method on gold substrate with patterned self-assemble monolayers (SAMs). First, we prepared ordered polymer dot arrays on the SAMs patterned gold substrate by SAMs-direct dewetting. Subsequently, by manipulating concentration-controlled dewetting process, ordered ring arrays were obtained on the dot arrays patterned surface under the protection of water droplets. Namely, ordered bull's-eye-like structure arrays were fabricated successfully. The mechanism of these two kinds of dewetting process has been investigated in detail. And due to these two steps were independent, different materials could be simply introduced to the current system. Therefore, ordered homogeneous and heterogeneous bull's-eye-like structure arrays such as poly(N-vinylcarbazole) (PVK) (dot)/PVK (ring), PVK/5,12-ditetradecylquinolino[2,3-b]acridine-7,14(5H,12H)-dione (DTQA), and PVK/Fe(3)O(4) nanoparticles were obtained. This straightforward method may open up new possibilities for practical use of microchips with binary heterogeneous structure arrays.


Trypsin digestion in immunoperoxidase staining.
The effect of trypsin digestion on the immunoperoxidase-PAP staining of paraffin sections from normal and abnormal tissue was studied. Trypsin treatment reduced background staining considerably, but enhanced specific staining. Results were, therefore, much easier to read. Possible reasons for this result are discussed.


The angiotensin I-converting enzyme (kininase II): progress in molecular and genetic structure.
The complete amino acid sequence of the human angiotensin I-converting enzyme (ACE) has been determined by protein sequencing of the purified kidney enzyme and cDNA cloning in endothelial cell libraries. The ACE molecule comprises 1,306 amino acids. It possesses a signal peptide of 29 residues cleaved off during maturation. The enzyme is most likely anchored to the plasma membrane by a short transmembrane domain situated near the carboxy-terminal extremity. Interestingly, the molecule presents a high degree of internal homology between two large peptidic domains. Each of these domains contains short sequences identical to zinc binding and active site sequences of other zinc metallopeptidases and therefore bears a putative active site. However, earlier experiments indicate only one zinc atom bound per molecule of ACE. Competitive inhibitors seem to interact with a unique class of high-affinity binding site. These observations may suggest that, despite the duplicated structure of the enzyme, there is only one functional active site per molecule of ACE. The respective role of the two homologous domains in this active site remains to be determined. A single gene coding for ACE is present in humans, transcribed as a 4.3-kilobase mRNA species in endothelial cells. In other studies, evidence for a genetic polymorphism in plasma ACE levels has been obtained by analyzing a large group of "healthy" nuclear families. A familial association of plasma ACE levels was observed. A major gene effect can possibly explain part of the interindividual variability observed in this enzyme.


Hydration and recognition of methylated CpG steps in DNA.
The analysis of the hydration pattern around methylated CpG steps in three high resolution (1.7, 2.15 and 2.2 A) crystal structures of A-DNA decamers reveals that the methyl groups of cytosine residues are well hydrated. In comparing the native structure with two structurally distinct forms of the decamer d(CCGCCGGCGG) fully methylated at its CpG steps, this study shows also that in certain structural and sequence contexts, the methylated cytosine base can be more hydrated that the unmodified one. These water molecules seem to be stabilized in front of the methyl group through the formation C-H...O interactions. In addition, these structures provide the first observation of magnesium cations bound to the major groove of A-DNA and reveal two distinct modes of metal binding in methylated and native duplexes. These findings suggest that methylated cytosine bases could be recognized by protein or DNA polar residues through their tightly bound water molecules.


Alcohol effects on luteinizing hormone-releasing hormone-stimulated luteinizing hormone and follicle-stimulating hormone in female rhesus monkeys.
The effects of acute alcohol administration on anterior pituitary function were studied in eight female rhesus monkeys during the follicular phase of the menstrual cycle. Integrated plasma samples were collected for 80 min before and 120 min after nasogastric intubation of alcohol (2.5 or 3.5 g/kg) or isocaloric sucrose control solution. Synthetic luteinizing hormone-releasing hormone (LHRH; 100 micrograms i.v.) was then administered, and plasma samples were collected for an additional 180 min. After sucrose control administration, LHRH stimulated a significant increase in both LH (P less than .001) and follicle-stimulating hormone (FSH) (P less than .004) within 30 and 80 min, respectively. After alcohol administration, LHRH-stimulated LH increased significantly (P less than .001) within 15 min when blood alcohol levels averaged 184 ( +/- 14.3) and 276 ( +/- 14.9)mg/dl. However, FSH levels remained equivalent to base line after alcohol and LHRH administration. The prevention by alcohol of LHRH stimulation of FSH during the follicular phase suggests that alcohol may attenuate normal follicular maturation, which in turn could result in luteal phase inadequacy or anovulation, conditions often observed in alcohol-dependent women and in animal models of alcoholism.


Potassium additive algorithm for use in continuous renal replacement therapy.
The performance of continuous renal replacement therapy (CRRT) brings about alterations in the serum potassium levels in patient. Potassium is an electrolyte essential for the regulation of nerve conduction and muscle contraction, particularly important in the case of cardiac muscle. This article describes the physiological mechanisms that affect potassium distribution throughout the body and also describes the effects of hypokalaemia or hyperkalaemia on the heart. This article justifies the need for serum potassium control during CRRT, which recognizes and reconciles the differing areas of responsibility of the medical and nursing staff. This article critically reviews the steps taken to develop and implement into clinical practice and evaluate a potassium additive algorithm. It also discusses the implications of this initiative.


Parasite-based screening and proteome profiling reveal orlistat, an FDA-approved drug, as a potential anti Trypanosoma brucei agent.
Trypanosoma brucei is a parasite that causes African sleeping sickness in humans and nagana in livestock and is transmitted by the tsetse fly. There is an urgent need for the development of new drugs against African trypanosomiasis due to the lack of vaccines and effective drugs. Orlistat (also called tetrahydrolipstatin or THL) is an FDA-approved antiobesity drug targeting primarily the pancreatic and gastric lipases within the gastrointestinal tract. It shows potential activities against tumors, mycobacteria, and parasites. Herein, we report the synthesis and evaluation of an expanded set of orlistat-like compounds, some of which showed highly potent trypanocidal activities in both the bloodstream form (BSF) and the procyclic form (PCF) of T. brucei. Subsequent in situ parasite-based proteome profiling was carried out to elucidate potential cellular targets of the drug in both forms. Some newly identified targets were further validated by the labeling of recombinantly expressed enzymes in Escherichia coli lysates. Bioimaging experiments with a selected compound were carried out to study the cellular uptake of the drug in T. brucei. Results indicated that orlistat is much more efficiently taken up by the BSF than the PCF of T. brucei and has clear effects on the morphology of mitochondria, glycosomes, and the endoplasmic reticulum in both BSF and PCF cells. These results support specific effects of orlistat on these organelles and correlate well with our in situ proteome profiling. Given the economic challenges of de novo drug development for neglected diseases, we hope that our findings will stimulate further research towards the conversion of orlistat-like compounds into new trypanocidal drugs.


Aspartate aminotransferase isotope exchange reactions: implications for glutamate/glutamine shuttle hypothesis.
Aspartate aminotransferase (AAT) catalyzes amino group transfer from glutamate (Glu) or aspartate (Asp) to a keto acid acceptor-oxaloacetate (OA) or alpha-ketoglutarate (KG), respectively. Data presented here show that AAT catalyzes two partial reactions resulting in isotope exchange between 3H-labeled Glu or 3H-labeled Asp and the cognate keto acid in the absence of the keto acid acceptor required for the net reaction. Tritiated keto acid product was detected by release of 3H2O from C-3 during base-induced enolization. Tritium released directly from C-2 (or C-3) by the enzyme was also evaluated and is a small fraction of that released because of exchange to the keto acid pool. Exchange is dependent on AAT concentration, time-dependent, proportional to the amino-to-keto acid ratio, and blocked by aminooxyacetate (AOA), an AAT inhibitor. Enzymatic conversion of [3H]KG to Glu by glutamic dehydrogenase (GDH) or of [3H]OA to malate by malic dehydrogenase (MDH) "protects" the label from release by base, showing that base-induced isotope release is from keto acid rather than a result of release during the exchange process. AAT isotope exchange is discussed in the context of the glutamate/glutamine shuttle hypothesis for astrocyte/neuron carbon cycling.


Reversible transdifferentiation of secretory epithelial cells into adipocytes in the mammary gland.
Mammalian breast adipose tissue is replaced by a milk-secreting gland during pregnancy; the reverse process takes place upon interruption of lactation. Morphological and bromodeoxyuridine studies provide indirect evidence that mouse mammary adipocytes transform into secretory epithelial cells during pregnancy and revert to adipocytes after lactation. By using the Cre-loxP recombination system we show that the mammary gland of whey acidic protein (WAP)-Cre/R26R mice, in which secretory epithelial cells express the lacZ gene during pregnancy, contains labeled adipocytes during involution. Conversely, adipocyte P2-Cre/R26R mice, in which adipocytes are labeled before pregnancy, contain labeled secretory epithelial cells during pregnancy. We conclude that reversible adipocyte-to-epithelium and epithelium-to-adipocyte transdifferentiation occurs in the mammary gland of adult mice during pregnancy and lactation.


Analysis of ras gene expression in stomach cancer by anti-ras p21 monoclonal antibodies.
Using anti-ras p21 monoclonal antibodies, RASK-3, which reacts with all of Ki-, N-, and Ha-ras p21, we examined by immunohistochemistry the expression of p21 in human gastric cancer (80 cases) and benign gastric lesions (32 cases). Ten percent formalin fixed tissues were studied. Ras p21 was positive in 51 cases (64%) out of 80 cases and partially positive in 12 cases (15%) at the cancerous areas. Ras p21 was partially positive in 7 cases (9%) at the noncancer areas of the same slides. Intestinal metaplasia and normal parietal cells were also often positive. In the study of 32 cases of benign stomach lesions, 2 out of 3 cases of atypical hyperplasia (ATP) and 3 out of 11 cases of stomach ulcer with regenerating epithelials were positive. Ras p21 was more dominantly expressed in the well-differentiated type of stomach cancer than the poorly differentiated type. Expression of ras p21, however, was not correlated either with the grades of cancer invasion or with the types of cancer infiltration.


Prevalence of overweight/obesity in relation to dietary habits and lifestyle among 7-17 years old children and adolescents in Lithuania.
Until recently increasing prevalence of overweight and obesity among pediatric population in Europe and worldwide contributes to major well-known risks for metabolic consequences in later life. The aim of this study was to determine the prevalence of overweight/obesity among children and adolescents in Lithuania and assess its association with energy balance related behaviors as well as familial demographic and socioeconomic factors. Cross-sectional study included 3990 7-17 years old schoolchildren from 40 schools of Kaunas region, Lithuania. Study participants underwent anthropometric measurements. Body mass index (BMI) was evaluated according to International Obesity Task Force (IOTF) criteria for children and adolescents. Children and adolescents and their parents filled in the questionnaires on parental sociodemographic characteristics, dietary habits, TV watching time, and family socioeconomic status. The prevalence of underweight, overweight, and obesity among boys and girls was 6.9 and 11.7 % (P < 0.05), 12.6 and 12.6 % (P > 0.05), and 4.9 and 3.4 % (P < 0.05), respectively. Obesity was significantly more prevalent in the 7-9 years old group (6.7 and 4.8 % in boys and girls, respectively, P < 0.05). Lower meals frequency and breakfast skipping were directly associated with overweight/obesity (P < 0.05); however, physical inactivity was not associated with higher BMI. Children's overweight/obesity was directly associated with lower paternal education and unemployment (OR 1.30, P = 0.013 and OR 1.56, P = 0.003, respectively). The prevalence of overweight and obesity among 7-17 years old Lithuanian children and adolescents was more prevalent in younger age, still being one of the lowest across the European countries. Meals frequency, breakfast skipping, paternal education and unemployment as well as a family history of arterial hypertension were found to be associated with children's and adolescents' overweight/obesity.


Batch pH Oscillations in the Belousov-Zhabotinsky Reaction.
No single-phase system has been previously reported to give significant pH oscillations in a closed (batch) reactor. We report here sustained pH oscillations in batch for the Belousov-Zhabotinsky reaction using much lower [H+]0 and much higher [BrO3-]0 than in traditional studies of this reaction. In fact, pH oscillations were obtained in the presence of only BrO3-, malonic acid (MA), and Mn2+. The amplitude, frequency, and duration of oscillations tend to depend primarily on the ratio of [BrO3-]0 to [MA]0. A critical part of the proposed mechanism involves the reversible formation of a manganese(III) complex with bromomalonic acid, followed by two-electron oxidation to tartraric acid and Mn2+. Estimates of the corresponding rate constant values for these reactions have been obtained by simulation. It is suggested that the presence of a supercatalytic reaction in H+ may be a sufficient, if not necessary, requirement for the occurrence of pH oscillations in a batch system.


Variation in HNF1B and Obesity May Influence Prostate Cancer Risk in African American Men: A Pilot Study.
Background. Prostate cancer (PCa) racial disparity is multifactorial, involving biological, sociocultural, and lifestyle determinants. We investigated the association between selected potentially functional polymorphisms (SNPs) and prostate cancer (PCa) risk in Black (AAM) and White (EAM) men. We further explored if these associations varied by the body mass index (BMI) and height. Methods. Age-matched DNA samples from 259 AAM and 269 EAM were genotyped for 10 candidate SNPs in 7 genes using the TaqMan allelic differentiation analysis. The dominant, recessive, and additive age-adjusted unconditional logistic regression models were fitted. Results. Three SNPs showed statistically significant associations with PCa risk: in AAM, HNF1B rs7501939 (OR = 2.42, P = 0.0046) and rs4430796 (OR = 0.57, P = 0.0383); in EAM, CTBP2 rs4962416 (OR = 1.52, P = 0.0384). In addition, high BMI in AAM (OR = 1.06, P = 0.022) and height in EAM (OR = 0.92, P = 0.0434) showed significant associations. Interestingly, HNF1B rs7501939 was associated with PCa exclusively in obese AAM (OR = 2.14, P = 0.0103). Conclusion. Our results suggest that variation in the HNF1B may influence PCa risk in obese AAM.


Partial characterization and time course analysis of Hymenolepis diminuta coproantigens.
An analysis of Hymenolepis diminuta specific antigens in infected rat faeces was carried out. Using a capture type antibody sandwich ELISA assay based on a hyperimmune rabbit anti-worm somatic antisera it was demonstrated that, although antigen was present in faeces before patency, the onset of egg production led to a sharp increase in the levels of parasite antigen in the faeces. Levels of antigen in host faeces were independent of worm burden. Parasite eggs did not contribute significantly to faecal antigen levels. Western blot analysis indicated a number of highly specific antigens at around M(r) 69,000, M(r) 37,000, M(r) 50,000 and M(r) 27,000 with a low molecular weight smear at between M(r) 30,000 and M(r) 34,000 present in the faeces of H. diminuta infected rats. Some cross reaction occurred with an antigen of around M(r) 66,000 in the faeces of non H. diminuta infected rodents. Antibody activity against this antigen was removed by affinity adsorption of the antibody solution against normal rat faeces.


Pharmacological treatments for drug misuse and dependence.
Substance misuse disorder (DSM-5) remains a major health challenge. Harm reduction is the initial treatment goal, by reducing or eliminating non-prescribed drug use. Eventual abstinence is the ultimate harm reduction goal. However the scope for evidence-based pharmacological interventions remains limited. The paper takes a pragmatic clinical approach to existing and developing pharmacotherapies for substance misuse. Dependence may be characterised as a cycle with three stages: binge/intoxication, withdrawal/negative affect and preoccupation/anticipation (craving). Each of these stages may be the focus of pharmacotherapeutic intervention, and current literature is discussed which is of relevance to the practising clinician. Dependence on opiates, stimulants, cannabis and prescribed medications including benzodiazepines and the current treatments are addressed. Possible pharmacotherapies of the future include anti-craving medications, which are still incompletely understood. Other developments include ultra-long-acting formulations, some of which have already been produced and are being studied or are in early clinical practice. A completely new line of investigation has been drug 'vaccines', whereby the body is stimulated to produce antibodies to, for example, cocaine and nicotine. Despite a number of evidence-based strategies for the treatment of substance misuse disorder, the range of licensed pharmacological treatment choices nevertheless remains narrow.


Macrophages Reprogrammed In Vitro Towards the M1 Phenotype and Activated with LPS Extend Lifespan of Mice with Ehrlich Ascites Carcinoma.
BACKGROUND The majority of tumors trigger macrophage reprogramming from an anti-tumor M1 phenotype towards a pro-tumor M2 phenotype. The M2 phenotype promotes tumor growth. We hypothesized that increasing the number of M1 macrophages in a tumor would limit carcinogenesis and extend the lifespan of the tumor host. The aim of this study was to verify this hypothesis in Ehrlich ascites carcinoma (EAC). The objectives were to evaluate effects of 1) EAC on a macrophage phenotype and NO-producing macrophage activity in vivo; 2) ascitic fluid from mice with EAC on a macrophage phenotype and NO-producing macrophage activity in vitro; and 3) in vitro reprogrammed M1 macrophages on lifespan of mice with EAC. MATERIAL AND METHODS The study was conducted using C57BL/6J mice. RESULTS Concentration of nitrite, a stable NO metabolite and an index of NO production, was measured spectrophotometrically. Shifts of macrophage phenotype were assessed by changes in NO production as well as by amounts of CD80, a marker of M1 phenotype, and CD206, a marker of M2 phenotype. The CD markers were measured by flow cytometry. Macrophages were reprogrammed towards the M1 phenotype using two reprogramming factors: 0% FBS and 20 ng/ml IFN-γ. The study results showed that 1) EAC inhibited the macrophage NO production in vivo and reprogrammed macrophages towards the M2 phenotype; 2) ascitic fluid of mice with EAC inhibited the macrophage NO production in vitro and reprogrammed macrophages towards the M2 phenotype; and 3) injection of in vitro reprogrammed M1 macrophages into mice with EAC significantly increased the lifespan of mice. CONCLUSIONS These findings suggest that promising biotechnologies for restriction of tumor growth could be developed based on the in vitro macrophage reprogramming.


Stenosis of the carotid bifurcation: subjective assessment compared with strict measurement guidelines.
Preliminary results of the North American Symptomatic Carotid Endarterectomy Trial (NASCET) have shown that endarterectomy is highly effective in preventing stroke in patients with 70% to 99% stenosis of the carotid bifurcation. These results are based on specific linear measurement criteria comparing the residual diameter of the lumen with that of the normal carotid beyond the bulb. These criteria may differ from subjective assessments of the severity of stenosis. Angiograms from 125 NASCET patients were analysed independently by three groups of reviewers. The first group consisted of three neuroradiologists, the second of two neurologists and one neurosurgeon and the third of three radiologists with neuroradiologic experience. The degree of stenosis was estimated, without measurement, as mild (1% to 29%), moderate (30% to 69%) or severe (70% to 99%), or the vessel was said to be occluded. These assessments were compared with the degree of stenosis as determined by the NASCET neuroradiologist on the basis of measurement. The subjective assessment of stenosis produced false-positive rates (for assessing stenosis of less than 70% as severe) ranging from 5% among the neuroradiologists to 16% among the radiologists. The false-negative rates (for assessing stenosis of 70% or more as less than severe) ranged from 12% to 22%. Therefore, a subjective rating of carotid stenosis may lead to erroneous estimation of the severity of disease. This problem has therapeutic implications, because carotid endarterectomy has been shown to benefit only patients with stenosis of greater than 70%, as assessed according to strict measurement guidelines.


[Reaction of human platelets from ACD and ACD-AG blood to hypotonic shock].
The hypotonic shock response (HSR) of human blood platelets, which reflects functional and morphological integrity of platelets and could be an useful in vitro parameter for demonstration of the in vivo viability of platelets destined for transfusion was investigated. Fresh platelet rich plasma (PRP) and platelet concentrates (PC) from ACD- and ACD-AG-blood were studied by measuring the light absorbance changes at 436 nm after lowering the osmolality to 178 mOsm/kg. The reversed reaction following hypotonic shock was calculated from the maximal slope of the return of the baseline and expressed as absorbance units/min, that second to be the most sensitive parameter of the HSR. The maximal slope of the reversal reaction was significantly higher in ACD-PRP than in ACD-AG-PRP. A statistical difference of the HSR between PRP and PC was found in ACD-blood but not in ACD-AG blood. It was pointed to the great biological deviation of the HSR.


First-principles electronic transport calculations in finite elongated systems: a divide and conquer approach.
We present a first-principles method for the evaluation of the transmittance probability and the coherent conductance through elongated systems composed of a repeating molecular unit and terminated at both ends. Our method is based on a divide and conquer approach in which the Hamiltonian of the elongated system can be represented by a block tridiagonal matrix, and therefore can be readily inverted. This allows us to evaluate the transmittance and the conductance using first-principles electronic structure methods without explicitly performing calculations involving the entire system. A proof of concept model based on a trans-polyacetylene chain bridging two aluminum leads indicates that our divide and conquer approach is able to capture all the features appearing in the transmittance probability curves obtained by a full scale calculation.


Single-centre prospective observational study on postdelivery room care.
As quality of care in the delivery room has major impact on outcome of preterm infants, multiple guidelines have been established in recent years. There is, however, little evidence on how to proceed during postdelivery room care, the time of transfer and admission to the neonatal intensive care unit (NICU). The aim of this study was to identify processes taking place during this period with potential impact on outcome. Prospective observational study. Single-centre German tertiary NICU. 40 inborn preterm infants undergoing postdelivery room care. Prevalence of prolonged duration of postdelivery room care, disconnections from the ventilator and positioning of preterm infants. Total duration of postdelivery room care and NICU admission procedures were shorter in infants transferred in a transport incubator compared with using a NICU care station from birth. Extremely low birth weight (ELBW) infants spend 8% of the time in prone position in contrast to 39% in non-ELBW. Total duration of disconnection from the ventilator was 50 s and was ten times longer in infants who had nasal CPAP compared with infants intratracheally intubated. Infants with nCPAP had longer duration of disconnection from the ventilator if body weight was >1000 g or if they were transferred in a transport incubator. Multiple parameters like birth weight or type of transport affect neonatal care during the postdelivery room period. Prospective studies are needed to identify and optimise parameters within this period that affect long-term outcome.


Reconfigurable electro-optical directed-logic circuit using carrier-depletion micro-ring resonators.
Here we demonstrate a reconfigurable electro-optical directed-logic circuit based on a regular array of integrated optical switches. Each 1×1 optical switch consists of a micro-ring resonator with an embedded lateral p-n junction and a micro-heater. We achieve high-speed on-off switching by applying electrical logic signals to the p-n junction. We can configure the operation mode of each switch by thermal tuning the resonance wavelength. The result is an integrated optical circuit that can be reconfigured to perform any combinational logic operation. As a proof-of-principle, we fabricated a multi-spectral directed-logic circuit based on a fourfold array of switches and showed that this circuit can be reconfigured to perform arbitrary two-input logic functions with speeds up to 3 GB/s.


An in vitro assay to evaluate the immunomodulatory effects of unrestricted somatic stem cells.
Unrestricted somatic stem cells (USSC) are cord blood stem cells that have been considered as candidates for the regulation of immune responses. Therefore, potential exists for their use in the suppression of immune response after transplantation surgery. The aim of this study was evaluation of the effect of USSC on mixed lymphocyte reaction (MLR) as a model for graft rejection. USSC and mesanchymal stem cells (MSC) were isolated and cultured from cord blood and bone morrow, respectively. The immunophenotypes of USSC and MSC were evaluated by flow cytometery and USSC and MSC were co-cultured with peripheral blood lymphocytes (PBL) in an MLR to evaluate the immunomodulatory effect of these cells as a percentage of the control response. Current study demonstrated that proliferation of lymphocytes in the MLR was decreased after treatment with USSC, in a similar fashion to that seen with MSC. It can be concluded that USSC have similar regulatory effects as MSC on the MLR, which can be used as an indicator for potential organ rejection after transplantation. Therefore, the immunregulatory effect of these cells could be used in the clinic during organ transplantation and in the management of autoimmunity.


Incidence and prevalence of hepatitis C among clients of a Brisbane methadone clinic: factors influencing hepatitis C serostatus.
The objective of this study was to describe the incidence and prevalence of hepatitis C infection among clients of a methadone program in Queensland. The clinical notes of clients receiving methadone for treatment of opiate dependence who first registered at the clinic after 1989 were perused for information about their serological status for hepatitis C and hepatitis B infections during a six-week period in 1994. We followed hepatitis C negative clients until August-September 1995. At study entry, 69 per cent of the clients were recorded as being hepatitis C positive. Of those who were negative, the seroconversion rate was 11 per 100 person-years. The high incidence and prevalence of hepatitis C among methadone clients emphasises the need for effective early intervention strategies to prevent the transmission of hepatitis C among injecting drug users.


Surgical management of diabetic foot complications: the Far North Queensland profile.
Foot complications in diabetes incur huge human and medical costs. There is a high incidence of complicated diabetes mellitus in Far North Queensland, particularly in the indigenous communities. An audit of 51 patients admitted to Cairns Base Hospital from July 1992 to December 1994 with diabetic foot complications requiring surgical intervention was performed. The majority of surgical procedures were for serious infections in neuropathic feet precipitated by minor trauma. Surgical procedures included debridement/drainage, minor amputation, major amputation and arterial bypass. Half of the patients required more than one procedure and/or multiple admissions. Average length of stay was 48 days. Indigenous patients were overrepresented in this audited group. Prevention or minimization of diabetic foot complications can be achieved only through improvement in education and vigilance at all levels of the treatment process from community to hospital. Special attention to the needs of indigenous communities with a high incidence of diabetes must be a feature of any future initiatives.


Concentrations of diazinon, chlorpyrifos, and bendiocarb after application in offices.
Airborne and surface concentrations of diazinon, chlorpyrifos (Dursban), and bendiocarb (Ficam) were measured at intervals up to 10 days after broadcast spray application onto the floors of seven offices. Results from this work can provide information to evaluate health hazards for workers and others entering treated buildings and can assist public agencies in setting guidelines or regulations. Diazinon and chlorpyrifos airborne concentrations peaked 4 hr after application at 163 and 27 micrograms/m3 of air sampled, respectively. The highest level of bendiocarb (2.7 micrograms/m3) was measured during treatment. Airborne concentrations measured for diazinon indicate that building occupants should not enter unventilated rooms for at least 2 days after spraying. Reentry into unventilated rooms 1 day after treatment with chlorpyrifos or bendiocarb would appear to be safe, however. Residues on aluminum plates and furniture were examined at intervals of up to 48 hr after spraying. In many cases, surface concentrations were higher at 24 or 48 hr than at 1 hr. Concentrations of residues removed from wood and painted metal furniture generally were higher than those on the aluminum plates. Peak residue concentrations were diazinon, 38 ng/cm2 of surface area sampled at 48 hr; chlorpyrifos, 5.9 ng/cm2 at 48 hr; and bendiocarb, 25 ng/cm2 at 1 and 24 hr. Workers who must enter buildings after insecticide application often are unaware of treatment plans and, therefore, are unable to take precautions to minimize their exposure. Inhalation and skin contact with insecticides can be reduced by providing office workers and building occupants with information on treatment times, health effects of insecticide overexposure, steps to take to reduce contact, and the perceived health risk. It is essential that treated areas be ventilated adequately before workers return to their offices.


Efficiency of antioxidant Avenanthramide-C on high-dose methotrexate-induced ototoxicity in mice.
Methotrexate (MTX) has been used in treating various types of cancers but can also cause damage to normal organs and cell types. Folinic acid (FA) is a well-known MTX antidote that protects against toxicity caused by the drug and has been used for decades. Since hearing loss caused by MTX treatment is not well studied, herein we aimed to investigate the efficiency of the antioxidant Avenanthramide-C (AVN-C) on high-dose MTX (HDMTX) toxicity in the ear and provide insights into the possible mechanism involved in MTX-induced hearing loss in normal adult C57Bl/6 mice and HEI-OC1 cells. Our results show that the levels of MTX increased in the serum and perilymph 30 minutes after systemic administration. MTX increased hearing thresholds in mice, whereas AVN-C and FA preserved hearing within the normal range. MTX also caused a decrease in wave I amplitude, while AVN-C and FA maintained it at higher levels. MTX considerably damaged the cochlear synapses and neuronal integrity, and both AVN-C and FA rescued the synapses. MTX reduced the cell viability and increased the reactive oxygen species (ROS) level in HEI-OC1 cells, but AVN-C and FA reversed these changes. Apoptosis- and ROS-related genes were significantly upregulated in MTX-treated HEI-OC1 cells; however, they were downregulated by AVN-C and FA treatment. We show that MTX can cause severe hearing loss; it can cross the blood-labyrinth barrier and cause damage to the cochlear neurons and outer hair cells (OHCs). The antioxidant AVN-C exerts a strong protective effect against MTX-induced ototoxicity and preserved the inner ear structures (synapses, neurons, and OHCs) from MTX-induced damage. The mechanism of AVN-C against MTX suggests that ROS is involved in HDMTX-induced ototoxicity.


Chronic evaluations of ventricular ejection phase dynamics during abdominal left ventricular assist device (ALVAD) pumping in the awake, unanesthetized calf.
In 1974, between 2 and 8% of the 50,000 adult patients undergoing cardiac surgery in this country succumbed in the early post-operative period from left ventricular failure, despite various methods of pharmacologic and/or mechanical support. Our laboratories have concentrated on the development, modification, evaluation, and validation of an abdominally positioned left ventricular assist device which has the potential of reducing these mortalities. Continuous testing in animals, for periods exceeding 2 mos, satisfied reliability, durability and longevity requirements. The cumulative results of these investigations were reviewed at the National Heart and Lung Institute on August 21, 1975. Authorization for clinical trials of the device according to specific criteria and protocols46 was approved on November 1, 1975. The ALVAD is now in the early stages of clinical testing. The results of the current experiments demonstrate that ventricular outflow impedance and prosthetic inflow impedance are the major determinants of left ventricular assist device hemodynamic effectiveness. By markedly reducing outflow impedance, the ALVAD profoundly lowers ventricular pressure-work and oxygen demands while simultaneously increasing ventricular performance and maintaining or augmenting systemic perfusion. Moreover, our studies indicate that improved device designs (intended for intermediate and long-term implantation) and maximal performance can be achieved by focusing on these central determinants.


Forsythoneosides A-D, Neuroprotective Phenethanoid and Flavone Glycoside Heterodimers from the Fruits of Forsythia suspensa.
Forsythoneosides A-D (1-4), four unusual adducts of a flavonoid unit fused to a phenylethanoid glycoside through a pyran ring or carbon-carbon bond, and four new phenylethanoid glycosides (5-8) were isolated from the fruits of Forsythia suspensa, together with nine known compounds. The structures of 1-8, including their absolute configurations, were elucidated by spectroscopic data as well as experimental and calculated electronic circular dichroism analysis. Compounds 2 and 4 inhibited PC12 cell damage induced by rotenone, and increased cell viability from 53.9 ± 7.1% to 70.1 ± 4.0% and 67.9 ± 5.2% at 0.1 μM, respectively.


PmrA/PmrB Two-Component System Regulation of lipA Expression in Pseudomonas aeruginosa PAO1.
Pseudomonas lipases are well-studied, but few studies have examined the mechanisms of lipase expression regulation. As a global regulatory protein, PmrA controls the expression of multiple genes such as the Dot/Icm apparatus, eukaryotic-like proteins, and secreted effectors. In this study, the effect of PmrA on expression of the lipase lipA in Pseudomonas aeruginosa PAO1 was investigated by knocking out or overexpressing pmrA, rsmY, and rsmA. PmrA regulated the expression of lipA at both the transcriptional and translational level although translation was the pivotal regulatory mechanism for lipA expression. PmrA also regulated the expression of rsmY. Using gel mobility shift assay and pmrA/rsmY double gene knock-out model, we showed that PmrA directly bound to the promoter sequence of rsmY to regulate lipA expression. Translation of lipA was activated by the PmrA/PmrB system via RsmA. Specifically, the Shine-Dalgarno (SD) sequence located at lipA mRNA was overlapped through combination between RsmA and the AGAUGA sequence, subsequently blocking the 30S ribosomal subunit to the SD sequence, leading to translational inhibition of lipA. Transcriptional repression of RsmY initiated translation of lipA through negative translational regulation of rsmA. In conclusion, this study demonstrated that in P. aeruginosa PAO1, PmrA mainly regulated rsmY expression at a translational level to influence lipA expression. RsmY primarily activated lipA translation via negative translational regulation of rsmA.


A Biomechanical Re-Examination of Physical Activity Measurement with Accelerometers.
ActiGraph is the most common accelerometer in physical activity research, but it has measurement errors due to restrictive frequency filtering. This study investigated biomechanically how different frequency filtering of accelerometer data affects assessment of activity intensity and age-group differences when measuring physical activity. Data from accelerometer at the hip and motion capture system was recorded during treadmill walking and running from 30 subjects in three different age groups: 10, 15, and >20 years old. Acceleration data was processed to ActiGraph counts with original band-pass filter at 1.66 Hz, to counts with wider filter at either 4 or 10 Hz, and to unfiltered acceleration according to "Euclidian norm minus one" (ENMO). Internal and external power, step frequency, and vertical displacement of center of mass (VD) were estimated from the motion capture data. Widening the frequency filter improved the relationship between higher locomotion speed and counts. It also removed age-group differences and decreased within-group variation. While ActiGraph counts were almost exclusively explained by VD, the counts from the 10 Hz filter were explained by VD and step frequency to an equal degree. In conclusion, a wider frequency filter improves assessment of physical activity intensity by more accurately capturing individual gait patterns.


The menstrual cycle in context, I: Affective syndromes associated with reproductive hormonal changes.
In some women, mood and behavioral changes appear to be linked to the menstrual cycle. New basic science data on steroid-brain interactions have renewed interest in the menstrual cycle as a naturalistic model for assessing gonadal steroid-induced mental and behavioral changes. The authors investigate similarities and differences in affective symptoms associated with reproductive-related gonadal steroid changes that span the life cycle of women, including the menstrual cycle, oral contraceptive use, pregnancy, the postpartum period, and perimenopause. Recommendations for reporting of symptoms and implications for future research are discussed.


Pharmacodynamic analysis of tumour perfusion assessed by 15O-water-PET imaging during treatment with sunitinib malate in patients with advanced malignancies.
We evaluated pharmacodynamic changes in tumour perfusion using positron emission tomography (PET) imaging with 15O-water to assess biological response to sunitinib, a multitargeted tyrosine kinase inhibitor. Patients with advanced malignancies received sunitinib 50 mg/day orally, once daily for 4 weeks on treatment, followed by 2 weeks off treatment, in repeated 6-week cycles. Quantitative measurement of tumour perfusion was assessed using 15O-water-PET at baseline and after 2 weeks of treatment. At least one reference tumour lesion was included in the fields of view and assessed at both time points. Patients also underwent 18 F-fluorodeoxyglucose (FDG)-PET imaging at baseline and after 2 and 4 weeks of treatment. Radiological response of the reference tumour lesion and overall radiological response were assessed at week 12. Serum pharmacokinetic and biomarker analyses were also performed. Data were available for seven patients. Compared with baseline, all patients experienced a decrease in reference tumour blood flow ranging from 20 % to 85 % and also a reduction in the FDG standard uptake value ranging from 29 % to 67 %. Six patients experienced a partial metabolic response based on FDG-PET criteria. Four patients had stable disease defined by radiological response (Response Evaluation Criteria in Solid Tumors) lasting between 4 and 12 cycles. An association between perfusion change and clinical benefit, and biomarker levels including vascular endothelial growth factor was observed. Administering sunitinib to patients with advanced malignancies is associated with early biological responses, including decreased blood flow in secondary tumour deposits.


Patient compliance with antibiotic treatment for respiratory tract infections.
Despite doctors' expectations, non-compliance is common in short-term antibiotic therapy of respiratory tract infections (RTIs). This phenomenon has profound practical implications. It leads to ineffective management, the deterioration of patients' health, hospital admissions, additional costs and the emergence of antibiotic-resistant microorganisms. This article reviews methods of measuring compliance with antibiotics in the outpatient-based management of RTIs and research results. Causes of non-compliance are also discussed. Factors influencing compliance are analysed, as well as practical strategies for addressing non-compliance with antibiotic therapies for RTIs. The influence of the frequency of doses on compliance is particularly stressed, as it has been observed that once daily dosing has almost a 100% compliance rate. As a number of once-daily antibiotic preparations are available now, the possibility of using once-daily schedules for improving compliance in RTI cases is stressed.


Surface-imprinted microspheres prepared by a template-oriented method for the chiral separation of amlodipine.
The surface imprinting technique has been developed to overcome the mass-transfer difficulty, but the utilization ratio of template molecules in the imprinting procedure still remains a challengeable task to be improved. In this work, specifically designed surface-imprinted microspheres were prepared by a template-oriented method for enantioseparation of amlodipine besylate. Submicron mesoporous silica microspheres were surface-modified with double bonds, followed by polymerizing methacrylic acid to generate carboxyl modified mesoporous silica microspheres (PMAA@SiO2 ). Afterwards, PMAA@SiO2 was densely adsorbed with (S)-amlodipine molecules to immobilize template molecules through multiple hydrogen bonding interactions. Then surface molecular imprinting was carried out by cross-linking the carboxyl group of PMAA@SiO2 with ethylene glycol diglycidyl ether. The surface-imprinted microspheres showed fast binding kinetics of only 20 min for equilibrium adsorption, and the saturation adsorption capacity reached 137 mg/g. The imprinted materials displayed appreciable chiral separation ability when used as column chromatography for enantioseparation of amlodipine from amlodipine besylate, and the enantiomeric excess of (S)-amlodipine reached 13.8% with only 2.3 cm column length by no extra chiral additives. Besides, the imprinted materials exhibited excellent reusability, and this allows the potential application for amplification production of amlodipine enantiomer.


Molecular, cytogenetic, and clinical investigations of Prader-Willi syndrome patients.
Thirty-seven patients presenting features of the Prader-Willi syndrome (PWS) have been examined using cytogenetic and molecular techniques. Clinical evaluation showed that 29 of these patients fulfilled diagnostic criteria for PWS. A deletion of the 15q11.2-q12 region could be identified molecularly in 21 of these cases, including several cases where the cytogenetics results were inconclusive. One clinically typical patient is deleted at only two of five loci normally included in a PWS deletion. A patient carrying a de novo 13;X translocation was not deleted for the molecular markers tested but was clinically considered to be "atypical" PWS. In addition, five cases of maternal heterodisomy and two of isodisomy for 15q11-q13 were observed. All of the eight patients who did not fulfill clinical diagnosis of PWS showed normal maternal and paternal inheritance of chromosome 15 markers; however, one of these carried a ring-15 chromosome. A comparison of clinical features between deletion patients and disomy patients shows no significant differences between the two groups. The parental ages at birth of disomic patients were significantly higher than those for deletion patients. As all typical PWS cases showed either a deletion or disomy of 15q11.2-q12, molecular examination should provide a reliable diagnostic tool. As the disomy patients do not show either any additional or more severe features than typical deletion patients do, it is likely that there is only one imprinted region on chromosome 15 (within 15q11.2-q12).


Effects of coordination of diammineplatinum(II) with DNA on the activities of Escherichia coli DNA polymerase I.
The effects of the reaction of cis- and trans-diamminedichloroplatinum(II) with DNA have been measured with regard to DNA synthesis, 3'-5' exonuclease (proofreading), and 5'-3' exonuclease (repair) activities of Escherichia coli DNA polymerase I. Both isomers inhibit DNA synthetic activity of the polymerase through an increase in Km values and a decrease in Vmax values for platinated DNA but not for the nucleoside 5'-triphosphates as the varied substrates. The inhibition is a consequence of lowered binding affinity between platinated DNA and DNA polymerase, and of a platination-induced separation of template and primer strands. Strand separation enhances initial rates of 3'-5' excision of [3H]dCMP from platinated DNA (proofreading), while total excision levels of nucleotides are decreased. In contrast to proofreading activity, the 5'-3' exonuclease activity (repair) discriminates between DNA which had reacted with cis- and with trans-diamminedichloroplatinum(II). While both initial rates and total excision are inhibited for the cis isomer, they are almost not affected for the trans isomer. This differential effect could explain why bacterial growth inhibition requires much higher concentrations of trans- than cis-diamminedichloroplatinum(II).


Association of Plasma Pro-Brain-Derived Neurotrophic Factor (proBDNF)/Mature Brain-Derived Neurotrophic Factor (mBDNF) Levels with BDNF Gene Val66Met Polymorphism in Alcohol Dependence.
BACKGROUND In a previous study, we reported that pro-brain-derived neurotrophic factor (proBDNF) was involved in the pathology of alcohol dependence, and the single-nucleotide polymorphism (SNP) Val66Met was located at the prodomain of the brain-derived neurotrophic factor gene (BDNF). This polymorphism has been reported to affect intracellular trafficking and activity-dependent secretion of BDNF. Our present research investigated the relationships between the BDNF Val66Met polymorphism and the plasma levels of proBDNF and mature brain-derived neurotrophic factor (mBDNF) in patients with alcohol dependence. MATERIAL AND METHODS The BDNF gene Val66Met polymorphism was genotyped in 59 alcohol-dependent patients and 37 age- and sex-matched controls, and the plasma levels of proBDNF and mBDNF were assessed by enzyme-linked immunosorbent assay in all participants. RESULTS No association was found between the BDNF gene Val66Met polymorphism and alcohol dependence (P>0.05). In comparison with the control group, the level of plasma proBDNF in the alcohol-dependence group was notably increased (Z=-2.228, P=0.026), while the level of mBDNF was remarkedly decreased (Z=-2.014, P=0.044). In the alcohol-dependence group, significant associations were not found between the Val66Met polymorphisms and proBDNF and mBDNF plasma levels (P>0.05). The plasma level of proBDNF was positively correlated with the average daily alcohol consumption in the last month (r=0.344, P=0.008) and drinking history (r=0.317, P=0.014), while the plasma level of mBDNF had negative effects (r=-0.361, P=0.005, with the average daily alcohol consumption; r=-0.427, P=0.001, with drinking history). CONCLUSIONS The BDNF gene Val66Met polymorphism does not appear to affect the secretion of proBDNF and mBDNF in Chinese patients with alcohol dependence. Furthermore, this study reconfirmed that the plasma levels of proBDNF and mBDNF were correlated with the average daily alcohol consumption in the last month and with drinking history.


Toxorhynchites rutilus septentrionalis: new occurrences in upstate New York.
Records of Toxorhynchites rutilus septentrionalis findings in New York State are few, and collections north of New York City are rare. This is the 1st official documentation of Tx. rutilus found in upstate New York in the past 46 years and the farthest northern record. In 2002, immatures of Tx. rutilus were found in artificial containers in 2 locations in the Hudson Valley region, at Quarryville (Ulster County) and Blauvelt (Rockland County), NY. A study conducted at Quarryville in 2002 and 2003 found that breeding occurred continuously through the season, and that overwintering possibly could be occurring at that site.


Structure and function of distance runners' heart.
To compare ultra-long distance runners' heart morphologic and functional parameters at rest with those of long distance runners' and middle distance runners'. Standard Doppler, M-mode and 2-D-mode echocardiography was performed at rest to 22 middle, 31 long and 11 ultra-long adult male distance runners. Long and ultra-long distance runners' left ventricular mass and left ventricular mass index were larger (p<0.05) than that of middle distance runners' (groups' means--approximately 288, 305 and 250 g as well as 153, 160 and 130 g/m(2), respectively) due to both larger (p<0.05) end-diastolic interventricular wall thickness (10.6, 11.1 and 9.8 mm, respectively) and left ventricular posterior wall thickness (10.7, 11.5 and 10.0 mm, respectively). Ultra-long distance runners' left ventricular mass and mass index did not differ significantly from long distance runners' (p>0.05), but end-diastolic posterior wall thickness was higher (p<0.05). Relative left ventricular wall thickness was larger in ultra-long distance runners as compared with middle distance runners (0.402 and 0.362, respectively; p<0.05). Ultra-long distance runners' right ventricular end-diastolic diameter was significantly larger (p<0.05) than that of middle and long distance runners (groups' means--25.8, 20.7 and 21.4 mm, respectively). Right ventricular end-diastolic free wall was thicker in ultra-long distance runners as compared with middle distance runners (groups' means--6.7 and 5.9 mm, respectively; p<0.05). Diastolic left ventricular function (evaluated as E/A) as well as end-diastolic left ventricular diameter (groups' mean--55.5-56.4 mm) did not differ between groups (p>0.05). The hypertrophy of ultra-long (as well as long) distance runners' myocardium of both ventricles is more pronounced than that of middle distance runners'.


Improving the quality of the coding of primary diagnosis in standardized discharge summaries.
We propose to design and test an information-processing model to participate in appraising the quality and the consistency of the coding, for billing, of Standardized Discharge Summaries (SDSs). We designed a model using both symbolic knowledge extracted from the NLM's UMLS and statistical knowledge. The aim is to retrieve from the ICD-10 terms recorded in a SDS the Principal Diagnosis (PD) at the time of coding. In 90% of cases the PD was retrieved 1st or 2nd in SDS including three ICD-10 codes or more. This model could contribute as part of an automated quality control process in a hospital information system by checking consistency in coded SDSs and improve the income of the hospital.


Awareness of cardiopulmonary resuscitation in medical-students and doctors in Rawalpindi-Islamabad, Pakistan.
To assess the level of awareness regarding basic and practical knowledge of cardiopulmonary resuscitation and its importance in the eyes of medical/dental students and doctors. The cross-sectional study was conducted in medical and dental colleges as well as hospitals of Rawalpindi and Islamabad, Pakistan, from June to September 2011. Non-probability convenience sampling was used and structured questionnaires on basic and practical knowledge of the procedure were distributed. The questionnaire had 26 items related to basic and advanced knowledge of the required skills. Doctors were divided into two groups based on their years of service and practice. Those with less than 5 years' experience were grouped as junior doctors, while rest as senior doctors. Descriptive statistics were employed to analyse the data using SPPS version 17 and Microsoft Excel. Percentages were worked out and the results were interpreted. Of the 1000 questionnaires distributed, 646 (64.6%) were received duly filled and represented the study sample. Of the 646 participants, 34 (5.26%) were dentists, 424 (65.63%) were medical students, 92 (14.24%) were doctors and 96 (14.86%) were dental students. Basic knowledge of doctors was found to be better than that of dentists (n = 96; 50% vs. n = 8; 23%). Similarly, the advance knowledge of doctors was better than the dentists (n = 53; 58% vs. n = 11; 31%). The basic knowledge of junior doctors was found to be almost equal to the senior doctors (n = 26; 44.75% vs. n = 15; 45.5%). The advance knowledge of junior doctors was found to be better than the senior doctors (n = 27; 45.37% vs. n = 10; 29.48%). Among the students, 157 (37%) of the medical students had basic knowledge of CPR, while 36 (38%) dental students had basic knowledge of the topic. Medical students had more advanced knowledge (n = 157; 37%) than dental students (n = 34; 35%). The awareness of basic and advance knowledge of cardiopulmonary resuscitation skills in medical/dental students and doctors in Rawalpindi and Islamabad was inadequate.


Senescence Can Be BETter without the SASP?
Global remodeling of the chromatin landscape occurs during senescence, although its functional consequence is still unclear. In this issue, Tasdemir and colleagues show that the epigenetic regulator BRD4 is required for expression of the proinflammatory senescence-associated secretory phenotype and immune clearance of senescent cells in vitro and in vivo Their results could be useful in the design of novel therapies to treat aging-related diseases, including cancer.Cancer Discov; 6(6); 576-8. ©2016 AACR.See related article by Tasdemir et al., p. 612.


[SOCIAL HEALTH OF PEOPLE WITH DISABILITIES IN THE CONTEXT OF SOCIAL CHANGE].
Absolutely all over the world there is a constant increase in the number of people with disabilities, as a result of a number of economic, social, ecological, demographic reasons. The share of disabled people on the territory of the Pridnestrovian Moldavian Republic has remained high in recent years. The article touches upon the issues of qualitative indicators of the social health of people with disabilities, gives a fundamental characteristic of social health. A questionnaire survey was conducted in February 2018 among people with disabilities, and for the purpose of additional study, interviews with people of working age with disabilities were conducted in March 2022. The results of the author's research on the territory of the Pridnestrovian Moldavian Republic among people with disabilities on the subject of studying the processes of socialization and social adaptation in society are presented. Based on the conducted quantitative and qualitative research methods, the main trends regarding the social health of people with disabilities were identified. The main barriers on the way to successful integration processes hindering socialization and social adaptation are outlined. The above results necessitate the modernization of the current system of targeted support for people with disabilities.


Control of calcium homeostasis by angiotensin II in adrenal glomerulosa cells through activation of p38 MAPK.
Angiotensin II-induced activation of aldosterone secretion in adrenal glomerulosa cells is mediated by an increase of intracellular calcium. We describe here a new Ca2+-regulatory pathway involving the inhibition by angiotensin II of calcium extrusion through the Na+/Ca2+ exchanger. Caffeine reduced both the angiotensin II-induced calcium signal and aldosterone production in bovine glomerulosa cells. These effects were independent of cAMP or calcium release from intracellular stores. The calcium response to angiotensin II was more sensitive to caffeine than the response to potassium, suggesting that the drug interacts with a pathway specifically elicited by the hormone. In calcium-free medium, calcium returned more rapidly to basal levels after angiotensin II stimulation in the presence of caffeine. Thapsigargin had no effect on these kinetics, but diltiazem, which inhibits the Na+/Ca2+ exchanger, markedly reduced the rate of calcium decrease and abolished caffeine action. The involvement of this exchanger was supported by the effect of cell depolarization and of a reduction of extracellular sodium on the rate of calcium extrusion. We also determined the mechanism of angiotensin II action on the exchanger. Phorbol esters reduced the rate of calcium extrusion, which was increased by baicalein, an inhibitor of lipoxygenases, and by SB 203580, an inhibitor of the p38 MAPK. Finally, we showed that angiotensin II acutely activates, in a caffeine-sensitive manner, p38 MAPK in glomerulosa cells. In conclusion, in bovine glomerulosa cells, the Na+/Ca2+ exchanger plays a crucial role in extruding calcium, and, by reducing its activity, angiotensin II influences the amplitude of the calcium signal. The hormone exerts its action on the exchanger through a caffeine-sensitive pathway involving the p38 MAPK and lipoxygenase products.


[Oxidative stress and antioxitant therapy of chronic periodontitis].
Chronic periodontitis is a progressive, infectious inflammation disease, caused by the dysbiosis of oral resident flora, leading to the destruction of periodontium. The onset of pathogenic microorganisms is the etiological factor of periodontitis, while the immuno-inflammatory response affects the progression of the disease. Under chronic periodontitis, oxidative stress occurs when excessive reactive oxygen species are produced and exceed the compensative capacity of the organism. Oxidative stress leads to the destruction of periodontium, in a direct way(damaging the biomolecule) or an indirect way(enhancing the produce of inflammatory cytokine and destructive enzymes). Therefore, as the antagonist of the reactive oxygen species, antioxidants may be helpful to treat the chronic periodontitis. This paper reviewed relevant literatures about the destructive role of excessive reactive oxygen species and protective role of antioxidants in chronic periodontitis.


Maximal respiratory pressure in healthy Japanese children.
[Purpose] Normal values for respiratory muscle pressures during development in Japanese children have not been reported. The purpose of this study was to investigate respiratory muscle pressures in Japanese children aged 3-12 years. [Subjects and Methods] We measured respiratory muscle pressure values using a manovacuometer without a nose clip, with subjects in a sitting position. Data were collected for ages 3-6 (Group I: 68 subjects), 7-9 (Group II: 86 subjects), and 10-12 (Group III: 64 subjects) years. [Results] The values for respiratory muscle pressures in children were significantly higher with age in both sexes, and were higher in boys than in girls. Correlation coefficients were significant at values of 0.279 to 0.471 for each gender relationship between maximal respiratory pressure and age, height, and weight, respectively. [Conclusion] In this study, we showed pediatric respiratory muscle pressure reference value for each age. In the present study, values for respiratory muscle pressures were lower than Brazilian studies. This suggests that differences in respiratory muscle pressures vary with ethnicity.


Complete cloning and sequencing of rat gp330/"megalin," a distinctive member of the low density lipoprotein receptor gene family.
We completed the cDNA cloning and sequencing of gp330, the major kidney glomerular antigen for rat Heymann nephritis. The deduced 4660-aa sequence, expected to constitute a mature protein of M(r) 516,715, consists of a probable N-terminal signal peptide sequence (25 aa), an extracellular region (4400 aa), a single transmembrane domain (22 aa), and a C-terminal cytoplasmic tail (213 aa). The extracellular region contains three types of cysteine-rich repeats characteristic of the low density lipoprotein receptor (LDLR) gene family--36 LDLR ligand-binding repeats forming four clusters of putative ligand-binding domains, 16 growth factor repeats separated by 8 YWTD spacer regions, and 1 C-terminal epidermal growth factor repeat. The cytoplasmic tail contains two copies of the (FX)NPXY motif, which represents a signal for coated pitmediated internalization and an additional similar motif. The overall structure of gp330 is similar to that of the LDLR-related protein (LRP)/alpha 2-macroglobulin receptor and shows even greater similarity to the Caenorhabditis elegans protein, reported as a homologue of LRP. However, gp330 differs from these proteins in (i) the cysteine-rich repeat arrangements found in the extreme extracellular N- and C-terminal regions, (ii) the distribution pattern of cysteine residues in the YWTD spacer regions, (iii) the location of the RX(K/R)R consensus recognition sequence of furin, a precursor processing endoprotease, and (iv) the length and structure of the cytoplasmic tail. We suggest the name megalin (from Greek mega) for gp330, the largest plasma membrane protein identified so far in vertebrates. The cloned cDNA will be useful for studies on the physiological functions of gp330/megalin and for determining its role in Heymann nephritis.


Beneficial effects of a high carbohydrate, high fiber diet on hyperglycemic diabetic men.
High carbohydrate diets rich in dietary fiber were fed to 13 hyperglycemic diabetic men; five men required 15 to 28 units of insulin per day, five men required sulfonylureas, and three men required 40 to 55 units of insulin. All 13 men were fed weight maintaining American Diabetic Association diets containing 43% of calories as carbohydrate for 1 week and then were fed 75% carbohydrate diets with 15 g of crude dietary fiber for approximately 2 weeks. After 2 weeks on the 75% carbohydrate diet, sulfonylureas were discontinued in all five men, insulin was discontinued in four men and decreased from 28 to 15 units in 1 man from the group requiring less than 30 units per day. Fasting plasma glucose values were significantly lower (P less than 0.001) in all 10 men. However, insulin requirements and fasting plasma glucose values were not changed in the three men requiring 40 to 55 units of insulin. Fasting serum cholesterol values were significantly (P less than 0.001) lower and mean fasting serum triglyceride values were 15% lower on the high carbohydrate diet than on the American Diabetic Association diet in these 13 men. Thus, a high carbohydrate diet with generous amounts of dietary fiber may be the treatment of choice of diabetic patients requiring sulfonylureas or less than 30 units of insulin per day.


Characterization of a salicylic acid- and pathogen-induced lipase-like gene in Chinese cabbage.
A cDNA clone for a salicylic acid-induced gene in Chinese cabbage (Brassica rapa subsp. pekinensis) was isolated and characterized. The cabbage gene, designated Br-sil1 (for Brassica rapa salicylate-induced lipase-like 1 gene), encodes a putative lipase that has the family II lipase motif GDSxxDxG around the active site serine. A database search showed that plant genomes have a large number of genes that contain the family II lipase motif. The lipase-like proteins include a myrosinase-associated protein, an anther-specific proline-rich protein APG, a pollen coat protein EXL, and an early nodule-specific protein. The Br-sil1 gene is strongly induced by salicylic acid and a nonhost pathogen, Pseudomonas syringae pv. tomato, that elicits a hypersensitive response in Chinese cabbage. Treatment of the cabbage leaves with BTH, methyl jasmonate, or ethephon showed that the Br-sil1 gene expression is induced by BTH, but not by methyl jasmonate or ethylene. This indicates that the cabbage gene is activated via a salicylic acid-dependent signaling pathway. An examination of the tissue-specific expression revealed that the induction of the Br-sil1 gene expression by BTH occurs in leaves and stems, but not in roots and flowers. Without the BTH treatment, however, the Br-sil1 gene is not expressed in any of the tissues that were examined.


Direct analysis of dried blood spots utilizing desorption electrospray ionization (DESI) mass spectrometry.
A novel approach to the quantitative determination of xenobiotics in whole blood samples without sample preparation or chromatography is described. This method is based on direct analysis of microlitre volumes of blood which are spotted onto specialized paper cards and dried, with the resulting dried blood spots (DBS) analyzed directly via desorption electrospray ionization (DESI) mass spectrometry (MS). Using sitamaquine, terfenadine, and prazosin as model compounds with verapamil as a common internal standard, this methodology demonstrated detection of each compound down to 10 ng mL(-1) from DBS where standard calibration curves show linearity from 10-10,000 ng mL(-1) with r(2) > 0.99. Three (3) different untreated types of filter papers (Whatman 903 and 31ETF as well as Ahlstrom 237) and two (2) treated types of filter paper (Whatman FTA and FTA Elute) were examined and the effect of each surface on the recovery of each analyte was evaluated. The results show that the untreated papers provide the best substrates for DBS analysis by DESI. A more in depth study of the quantitation of sitamaquine on 31ETF paper stock provided bias and error measurements of less than 20%. The promising results shown in this study may have important implications in the areas of therapeutic drug monitoring (TDM), clinical and forensic toxicology, and pharmacology.


DFT coupled with NEGF study of a promising two-dimensional channel material: black phosphorene-type GaTeCl.
A stable three-dimensional layered GaTeCl bulk counterpart is first known from experiment since 1980s. In this study, we propose a two-dimensional GaTeCl, the band structure of which has a tendency of intrinsic direct-to-indirect band gap transitions as a result of a decrease in the layer number, while the changes in the band gap value are minor. The GaTeCl monolayer possesses a wide indirect band gap of 3.06 eV and high hole mobility of up to 4710 cm2 V-1 s-1, which, intriguingly, can be converted into direct band-gap semiconductors under a slight tensile strain. The GaTeCl monolayer is calculated to have an ideal cleavage energy of about 32 meV per atom; therefore, the synthesis of GaTeCl monolayer through exfoliation of bulk GaTeCl is available. In this regard, we simulate a monolayer GaTeCl MOSFETs device based on first-principles method quantum transport approach. The underlying device performance could pave the way for it to be a promising candidate as a suitable FET channel material.


Functions of long non-coding RNA LNC11649 in non-small cell lung cancer cells as a reprocessed form of MALAT1.
Long non-coding RNAs (lncRNAs) have received much attention concerning their expression mechanisms in tumor formation. It is known that lncRNAs are involved in the occurrence, development, and prognosis of various tumors, including lung cancer. In our study, one non-coding RNA, LNC11649 (649 nt in length), was identified in non-small cell lung cancer (NSCLC) by PacBio third-generation sequencing technology. Both northern blot and quantitative PCR analyses confirmed the presence of LNC11649 in NSCLC tissues and cells with high expression. Its sequence was found to be highly homologous to lncRNA MALAT1. Knocking down MALAT1 could lead to a significant downregulation of LNC11649 content, revealing the possibility that LNC11649 could originate from MALAT1 reprocessing. RNA immunoprecipitation and electrophoretic mobility shift assays confirmed an interaction between LNC11649 and the MSI1 protein. Further experiments revealed that LNC11649 promoted the cytoplasmic distribution of MSI1 through its interaction with MSI1 and then activated the Akt signaling pathway to regulate the proliferation and migration of NSCLC cells. Our study reveals the possibility that LNC11649 plays a cancer-promoting role as a reprocessed form of MALAT1 in NSCLC cells and suggests that the MALAT1/LNC11649/MSI1/Akt regulatory axis becomes a potential therapeutic target for lung cancer.


Single-chain antibodies produced by phage display against the C-terminal 19 kDa region of merozoite surface protein-1 of Plasmodium yoelii reduce parasite growth following challenge.
Antibodies have the potential to be therapeutic reagents for malaria. Here we describe the production of a novel phage antibody display library against the C-terminal 19kDa region of the Plasmodium yoelii YM merozoite surface protein-1 (MSP1(19)). In vivo studies against homologous lethal malaria challenge show an anti-parasite effect in a dose dependent manner, and analysis by plasmon resonance indicates binding to the antigen is comparable to the binding of a protective monoclonal antibody. The data support the lack of a need for any antibody Fc-related function and hold great significance for the development of a therapeutic reagent for malaria.


MgO encapsulated mesoporous zeolite for the side chain alkylation of toluene with methanol.
Side chain alkylation of toluene with methanol was studied over mesoporous zeolite supported MgO catalysts. MgO were supported onto the carbon templated mesoporous silicalite-1 by direct synthesis route under microwave conditions. This direct synthesis route yields the majority of MgO highly dispersed into the mesopores of the silicalite-1 crystals. The vapor phase alkylation of toluene with methanol was performed over these catalysts under vapor phase conditions at atmospheric pressure. Mesoporous silicalite-1 supported MgO catalysts gave improved yields towards side chain alkylated products compared to the bulk MgO. The higher activity exhibited by 5% MgO supported on mesoporous silicalite compared to the one with 1% MgO can be attributed to the large number of weak basic sites observed from the CO2 TPD.


Population-based assessment of survival after cytoreductive nephrectomy versus no surgery in patients with metastatic renal cell carcinoma.
To examine the population-based survival rates of patients with metastatic renal cell carcinoma (RCC) treated with cytoreductive nephrectomy (CNT) and compare them with those of patients treated without surgery. Of the 43,143 patients with RCC identified in the 1988-2004 Surveillance, Epidemiology, and End Results database, 5372 had metastatic RCC. Of those, 2447 were treated with CNT (45.5%) and 2925 (54.5%) were not. Univariable and multivariable Cox regression models, as well as matched and unmatched Kaplan-Meier survival analyses, were used. The covariates consisted of age, sex, tumor size, and year of diagnosis. The 1-, 2-, 5-, and 10-year overall survival rate of the patients treated with CNT was 53.6%, 36.3%, 19.4%, and 12.7% compared with 18.5%, 7.4%, 2.3%, and 1.2% for the no-surgery patients, respectively. The corresponding cancer-specific survival rates were 58.1%, 40.8%, 24.3%, and 18.8% and 24.4%, 11.0%, 4.1%, and 2.9% for the same patient groups. On multivariate analysis, independent predictor status was recorded for treatment type, tumor size, and patient age (all P <.001). Also, relative to CNT, the no-surgery group had a 2.5-fold greater rate of overall and cancer-specific mortality (P <.001). In the matched analyses, virtually the same effect was recorded (hazard ratio 2.6, P <.001). The results of our study have shown that CNT significantly improves the survival of patients with metastatic RCC.


Induction of p16(INK4a) is the major barrier to proliferation when Epstein-Barr virus (EBV) transforms primary B cells into lymphoblastoid cell lines.
To explore the role of p16(INK4a) as an intrinsic barrier to B cell transformation by EBV, we transformed primary B cells from an individual homozygous for a deletion in the CDKN2A locus encoding p16(INK4a) and p14(ARF). Using recombinant EBV-BAC viruses expressing conditional EBNA3C (3CHT), we developed a system that allows inactivation of EBNA3C in lymphoblastoid cell lines (LCLs) lacking active p16(INK4a) protein but expressing a functional 14(ARF)-fusion protein (p14/p16). The INK4a locus is epigenetically repressed by EBNA3C--in cooperation with EBNA3A--despite the absence of functional p16(INK4a). Although inactivation of EBNA3C in LCLs from normal B cells leads to an increase in p16(INK4a) and growth arrest, EBNA3C inactivation in the p16(INK4a)-null LCLs has no impact on the rate of proliferation, establishing that the repression of INK4a is a major function of EBNA3C in EBV-driven LCL proliferation. This conditional LCL system allowed us to use microarray analysis to identify and confirm genes regulated specifically by EBNA3C, independently of proliferation changes modulated by the p16(INK4a)-Rb-E2F axis. Infections of normal primary B cells with recombinant EBV-BAC virus from which EBNA3C is deleted or with 3CHT EBV in the absence of activating ligand 4-hydroxytamoxifen, revealed that EBNA3C is necessary to overcome an EBV-driven increase in p16(INK4a) expression and concomitant block to proliferation 2-4 weeks post-infection. If cells are p16(INK4a)-null, functional EBNA3C is dispensable for the outgrowth of LCLs.


CCL22-producing CD8α- myeloid dendritic cells mediate regulatory T cell recruitment in response to G-CSF treatment.
G-CSF prevents type 1 diabetes in the NOD mouse by promoting the local recruitment of T regulatory cells (Tregs). This is an indirect effect because adoptive transfer of G-CSF-induced tolerogenic dendritic cells (DCs) promotes Treg accumulation. However, the identity of the particular DC subset and the molecule(s) mediating this effect remain unknown. We demonstrate in this study that the adoptive transfer of CD11c(high)CD8α(-) DCs isolated from pegylated G-CSF (pegG-CSF) recipients, but not that of other DC subtypes, enhanced the pancreatic recruitment of CD4(+)CD25(+)Foxp3(+) Tregs, which generated increased amounts of TGF-β. Likewise, only CD11c(high)CD8α(-) DCs from pegG-CSF recipients secreted the chemokine CCL22 at levels that effectively attracted Tregs. PegG-CSF was more efficient at enhancing the synthesis of CCL22 by CD11c(high)CD8α(-) DCs from the pancreatic lymph nodes compared with those from the spleen. Accordingly, CD11c(high)CD8α(-) DCs from the pancreatic lymph nodes of pegG-CSF recipients were more efficient than their splenic counterparts in the recruitment of Tregs upon adoptive transfer. Predictably, CD11c(high)CD8α(-) DCs failed to recruit these Tregs both in vivo and in vitro following intracellular neutralization of CCL22. These data assign a key role to CD8α(-) DCs and CCL22 in Treg recruitment in the protection of NOD mice against type 1 diabetes following the treatment with G-CSF.


Evidence From Qualitative Studies of Youth About the Impacts of Tobacco Control Policy on Young People in Europe: A Systematic Review.
A range of tobacco control policies endeavor to prevent smoking uptake in young people, yet relatively little is known about how such interventions impact young people's engagement with smoking. We reviewed existing qualitative evidence on young people and smoking in Europe to assess whether, in what ways and why young people comply with, adapt to, resist, or circumvent tobacco control policies in their respective countries. We undertook a systematic review of academic literature presenting qualitative research from Europe on smoking and young people (11-18 years), published from 2000 to 2015. Bibliographic searches (PubMed, PsycInfo, SSCI) produced 1357 records, from which 43 relevant articles were assessed for quality and 39 included in the review. Most studies were from the United Kingdom (27), with a small number (one or two each) from other European countries (Denmark, Sweden, Switzerland, Belgium, Cyprus, Greece, Hungary, Ireland, and Spain). Only 16 articles (11 from United Kingdom) provided any evidence about the impacts of tobacco control policies on young people's smoking. These focused on smoke-free legislation (four), age of sale laws (four), plain packaging (three), and black market tobacco (one). There is very little qualitative evidence exploring the impacts of tobacco control on youth smoking in Europe. To develop more effective smoking prevention policies that take account of local political, social, and cultural contexts, more qualitative research from a wider range of European countries is needed to understand how tobacco control impacts on young people's social worlds and smoking behaviors. Smoking is the leading cause of premature mortality in Europe. However, there is little qualitative evidence exploring the impact of tobacco control policies on young people in Europe. Most comes from the United Kingdom and focuses on a narrow range of policies. Thus, we have a limited understanding of how and in what ways tobacco control policies reach young people, their engagement with these, and how local context affects their impact. More qualitative research is needed, from a wider range of countries and on a broader range of tobacco control policies, to strengthen the evidence-base for reducing youth smoking.