3D Printed and Microcontrolled: The One Hundred Dollars Scanning Electrochemical Microscope.
The design and fabrication of a versatile and low-cost electrochemical-scanning probe microscope (EC-SPM) is presented. The proposed equipment relies on the use of modern prototyping tools such as 3D printers and microcontroller boards and only a few "off-the-shelf" parts to deliver a simple yet powerful EC-SPM equipment capable of performing simple space-resolved electrochemical measurements. The equipment was able to perform space-resolved electrochemical measurements using a platinum ultramicroelectrode (UME) as the working electrode on a scanning electrochemical microscopy (SECM) configuration and was used to record approach curves, line scans, and array scans over an insulating substrate. The performance of the proposed equipment was found to be adequate for simple SECM measurements under hindered diffusion conditions. Because of its flexible design (software and hardware), more complex array scan patterns, only found on high-end EC-SPM setups such as hopping mode scan, were easily implemented on the built equipment. Despite its simplicity, the versatility and low cost of the proposed design make it an attractive alternative as a teaching platform as well as a platform for developing more elaborate EC-SPM setups.


Boosting styrene epoxidation via CoMn2O4 microspheres with unique porous yolk-shell architecture and synergistic intermetallic interaction.
Achieving satisfactory organic transformation reactions under mild conditions using high-performance catalysts that are composed of cost-effective and earth-abundant elements has always been an aspiration for scientists in the field of catalysis. In this work, CoMn2O4 microspheres with intriguing porous yolk-shell architecture have been constructed by a facile solvothermal reaction and post-calcination treatment, and were employed for the first time in the epoxidation reaction of styrene (SER). Among the series of CoMn2O4 catalysts, the one calcined at 600 °C (CMO-600) displays superior catalytic performance in the SER, achieving an excellent conversion of 97.7%, a prominent selectivity of 83.7% to SO and a good recycling performance. The remarkable SER performance of the CMO-600 benefits from the collaborative influences derived from the unique porous yolk-shell architecture and the synergy of the two metal centers regarding high surface Mn2+/ Mn3+ atomic ratio, abundant redox couples and rich oxygen vacancies. The reaction pathway analysis and the activation energy measurement were performed as well to unravel the inner relationship between the catalytic behavior and the catalyst properties. This study affords a fresh impetus to the developing of high-performance bimetallic oxides for oxidation reactions in organic catalysis.


Bacterial Etiology and Antibiotic Resistance Patterns in Neonatal Sepsis in Tehran during 2006-2014.
Neonatal sepsis is one of the leading causes of mortality in neonatology wards. The aim of this study was to assess sepsis pathogens and antibacterial resistance patterns in a teaching hospital during seven years in Tehran, Iran. In this retrospective study, all neonates suspected to sepsis and fulfilling the sepsis criteria admitted to NICU ward of Mustafa Khomeini Hospital, Tehran, Iran during 2007 to 2014 were included. Demographic information, blood test results, blood culture results of neonates and antibiogram findings were extracted from their documents. Data was analyzed using SPSS 15. Ninety neonates with positive culture test were included. Fifty-three were male (58.9%). Thirty neonates were delivered vaginally (33.3%) and 60 caesarean section (66.7%). Most bacterial growths in culture were Staphylococcus aureus and E. coli. The rates of resistance for antibiotics like ceftriaxone, cefotaxim and gentamycin were 5%, 30% and 15%, correspondingly. There were 15 cases (16.7%) with resistance to imipenem. Antibacterial resistance patterns vary in different parts of the world and even within a country, therefore assessing resistance patterns in a region is of great importance for proper management and treatment. Our findings might help physicians for proper selection of antibiotics for treatment of neonatal sepsis.


Natriuretic hormones in brain function.
Natriuretic hormones (NH) include three groups of compounds: the natriuretic peptides (ANP, BNP and CNP), the gastrointestinal peptides (guanylin and uroguanylin), and endogenous cardiac steroids. These substances induce the kidney to excrete sodium and therefore participate in the regulation of sodium and water homeostasis, blood volume, and blood pressure (BP). In addition to their peripheral functions, these hormones act as neurotransmitters or neuromodulators in the brain. In this review, the established information on the biosynthesis, release and function of NH is discussed, with particular focus on their role in brain function. The available literature on the expression patterns of each of the NH and their receptors in the brain is summarized, followed by the evidence for their roles in modulating brain function. Although numerous open questions exist regarding this issue, the available data support the notion that NH participate in the central regulation of BP, neuroprotection, satiety, and various psychiatric conditions, including anxiety, addiction, and depressive disorders. In addition, the interactions between the different NH in the periphery and the brain are discussed.


Directed evolution of cell size in Escherichia coli.
In bacteria, cell size affects chromosome replication, the assembly of division machinery, cell wall synthesis, membrane synthesis and ultimately growth rate. In addition, cell size can also be a target for Darwinian evolution for protection from predators. This strong coupling of cell size and growth, however, could lead to the introduction of growth defects after size evolution. An important question remains: can bacterial cell size change and/or evolve without imposing a growth burden? The directed evolution of particular cell sizes, without a growth burden, was tested with a laboratory Escherichia coli strain. Cells of defined size ranges were collected by a cell sorter and were subsequently cultured. This selection-propagation cycle was repeated, and significant changes in cell size were detected within 400 generations. In addition, the width of the size distribution was altered. The changes in cell size were unaccompanied by a growth burden. Whole genome sequencing revealed that only a few mutations in genes related to membrane synthesis conferred the size evolution. In conclusion, bacterial cell size could evolve, through a few mutations, without growth reduction. The size evolution without growth reduction suggests a rapid evolutionary change to diverse cell sizes in bacterial survival strategies.


Sporamin induces apoptosis and inhibits NF-κB activation in human pancreatic cancer cells.
Sporamin, a Kunitz-type trypsin inhibitor (TI) from sweet potato tuberous roots, has demonstrated anti-tumor activity through poorly defined mechanisms. Furthermore, the effects of sporamin on pancreatic cancer have not been explored. Herein, we studied the effects of sporamin on two human pancreatic cancer cell lines, PANC-1 and BxPC-3. Sporamin significantly inhibited the cell viability and proliferation activity and induced apoptosis in PANC-1 and BxPC-3 cells. Consistently, in sporamin-treated PANC-1 and BxPC-3 cells, the anti-apoptotic proteins Bcl-2 and Bcl-XL were downregulated and the pro-apoptotic protein Bax was upregulated. Moreover, nuclear factor kappa B activation and IκBα phosphorylation were inhibited, and total IκBα expression was increased in sporamin-treated PANC-1 and BxPC-3 cells. Thus, our results suggest that the anti-tumor effects of sporamin in pancreatic cancer cells might result partly from induction of apoptosis by downregulating nuclear factor kappa B pathway.


Quantum dynamics of hydrogen atoms on graphene. I. System-bath modeling.
An accurate system-bath model to investigate the quantum dynamics of hydrogen atoms chemisorbed on graphene is presented. The system comprises a hydrogen atom and the carbon atom from graphene that forms the covalent bond, and it is described by a previously developed 4D potential energy surface based on density functional theory ab initio data. The bath describes the rest of the carbon lattice and is obtained from an empirical force field through inversion of a classical equilibrium correlation function describing the hydrogen motion. By construction, model building easily accommodates improvements coming from the use of higher level electronic structure theory for the system. Further, it is well suited to a determination of the system-environment coupling by means of ab initio molecular dynamics. This paper details the system-bath modeling and shows its application to the quantum dynamics of vibrational relaxation of a chemisorbed hydrogen atom, which is here investigated at T = 0 K with the help of the multi-configuration time-dependent Hartree method. Paper II deals with the sticking dynamics.


Decreased withdrawal symptoms but normal tolerance to nicotine in mice null for the alpha7 nicotinic acetylcholine receptor subunit.
Withdrawal symptoms are a major deterrent when people try to quit smoking. The alpha7 subunit of the neuronal nicotinic acetylcholine receptor (nAChR) is highly expressed in the brain, and has been suspected to play a major role in nicotine addiction. We studied the influence of alpha7-containing nAChRs on nicotine withdrawal and tolerance, in wild type mice and mice null for the alpha7 nAChR subunit (alpha7 -/-). For withdrawal experiments, animals were implanted with osmotic minipumps delivering nicotine for 13 days. A single intraperitoneal injection of the nAChR antagonists mecamylamine (MEC) or methyllycaconitine (MLA) was used to precipitate withdrawal. In wild type mice, both MEC- and MLA-precipitated somatic signs of withdrawal such as increased grooming, scratching and shaking. In alpha7 -/- mice, the somatic effects of MEC-precipitated nicotine withdrawal were significantly reduced. Interestingly, the presumed alpha7-specific antagonist MLA also precipitated withdrawal. Tolerance, which was measured as a decrease in nicotine-induced hypolocomotion after subchronic nicotine treatment, was normal in alpha7 -/- mice. Finally, because anxiety and withdrawal symptoms are highly correlated in humans, we studied anxiety-like behaviors in alpha7 -/- mice using a battery of anxiety-related tests. The behavior of alpha7 -/- mice was indistinguishable from that of control mice. Our results point to the alpha7 subunit as one of the players in nicotine withdrawal, but not in nicotine tolerance or basal anxiety-like behavior.


Protein excretion patterns in cadmium-exposed individuals: high resolution electrophoresis.
High resolution electrophoresis was used to evaluate protein excretion patterns in six cadmium-exposed individuals with proteinuria, seven subjects with nonspecific nephropathies, and four normal unexposed subjects. The aim of the investigation was to determine (a) the type of excretion pattern (i.e., glomerular, tubular, or mixed) associated with cadmium exposure and (b) if the pattern in the cadmium-exposed individuals was distinctly different from subjects with nonspecific nephropathies. The electrophoretic results were consistent with the quantitative results for the cadmium-exposed workers. The results suggest that the pattern associated with cadmium exposure can be glomerular or mixed and that it is different (i.e., no gamma band) from nonspecific nephropathies.


[Drugs in chronic venous insufficiency--the challenge of demonstrating clinical efficacy].
Approximately 90% of German adults show alterations of their lower limb veins; about every fifth suffers from symptoms of chronic venous insufficiency (CVI). With compression therapy showing low compliance, CVI oedemas and accompanying subjective symptoms are frequently treated with anti-oedematous drugs of herbal origin. A guideline outlines the requirements for clinical studies with CVI drugs. Water displacement plethysmometry (volumetry) is the gold standard for determining the reduction ofoedemas. Besides reducing oedemas, drugs should also demonstrate effects on accompanying symptoms influencing quality of life. Despite assistance provided by the guideline, clinical studies in CVI are complex and subject to multiple error sources in planning and execution. The corroboration of successful studies in further confirmatory studies is good practice and demanded by regulatory authorities. This practice reduces the risk of drugs being accepted as effective just based on the play of chance. As an example, placebo controlled studies with an extract from red vine leaves show that a careful definition of patients as well as meticulous study planning and execution can reproducibly verify significant and clinically relevant treatment effects. When evaluating clinical studies it is recommended to refer to the CONSORT statement. Publications missing certain minimum information make interpretation difficult and may result in a biased judgment of the effects of therapy.


Hyperscroll dynamics: Vortices in four-dimensional networks.
We investigate a network of excitable nodes diffusively coupled to their neighbors along four orthogonal directions. This regular network effectively forms a four-dimensional reaction-diffusion system and has rotating wave solutions. We analyze some of the general features of these hyperscroll waves, which rotate around surfaces such as planes, spheres, or tori. The surfaces evolve according to local curvatures and a system-specific surface tension. They have associated local phases and phase gradients tend to decrease over time. We also discuss the robustness of these network states against the removal of random node connections and report an example of hyperscroll turbulence.


Linkage of progestin and epidermal growth factor signaling: phosphorylation of progesterone receptors mediates transcriptional hypersensitivity and increased ligand-independent breast cancer cell growth.
Progesterone receptor (PR) action is linked to epidermal growth factor (EGF) initiated signaling pathways at multiple levels; mitogen-activated protein kinases (MAPKs) are key mediators of this important cross-talk. Herein, we probed the effects of EGF on PR function and regulation of breast cancer cell growth. EGF stimulated rapid and transient phosphorylation of PR-B Ser294 relative to persistent phosphorylation of this site induced by the synthetic progestin, R5020. EGF induced nuclear translocation and DNA binding of unliganded wild-type, but not mutant PRs containing an Ala at position 294 (S294A). However, EGF alone induced little to no PR-B transcriptional activity; S294A PR-B was transcriptionally impaired. In contrast, pretreatment of cells with EGF (30min) significantly increased the potency and efficacy of wild-type, but not S294A PR transcriptional activity in response to progestin, and enhanced ligand-dependent downregulation of wild-type but not S294A PR. Replacement of Ser294 with aspartic acid (S294D) to mimic phosphorylation at this site decreased receptor stability and, as predicted, heightened progestin-induced transcription relative to wild-type PR-B. RT-PCR demonstrated the Ser294 phosphorylation-dependence of selected PR target genes (TGFalpha and HB-EGF). Surprisingly, PR-B expressing cells growing in soft agar were highly responsive to EGF or progestin, and this was further stimulated by the combination of both hormones. Cells expressing S294A PR exhibited reduced soft agar growth, and were also sensitive to R5020 alone, but failed to respond to EGF. These results suggest that PR Ser294 is an important "sensor" for growth factor inputs that affects PR function and breast cancer cell growth in the absence of progestin or in the presence of low or "sub-threshold" progestin concentrations. PR function likely contributes to breast cancer progression when EGFR family members or their ligands are overexpressed, a condition that predicts low abundance, but highly active and nuclear PR.


Role of dietary factors in cell replication and colon cancer.
Human studies and experimental data from animals suggest that high rates of colonic epithelial cell replication enhance the development of colon cancer. Vegetarians and individuals following a prudent diet have lower rates of colorectal cell proliferation than subjects at high risk for colon cancer. Animal studies show that colonic cell proliferation is stimulated by feeding in general and specifically by a number of dietary fibers, fats, bile acids, and short-chain fatty acids. Many of these growth factors also increase the induction of experimental tumorigenesis. On the other hand factors that reduce cell growth, including ascorbic acid and butylated hydroxyanisole, inhibit colon carcinogenesis. These results support the concept that dietary chemoprevention is feasible and could significantly reduce the rate of colon cancer development in high risk populations.


Sleep problems contribute to post-concussive symptoms in service members with a history of mild traumatic brain injury without posttraumatic stress disorder or major depressive disorder.
Many with a history of mild traumatic brain injury (TBI) experience sleep problems, which are also common symptoms of stress-related and mood disorders. To determine if sleep problems contributed unique variance to post-concussive symptoms above and beyond symptoms of posttraumatic stress disorder/major depressive disorder (PTSD/MDD) after mild TBI. 313 active duty service members with a history of mild TBI completed sleep, PTSD, and mood symptom questionnaires, which were used to determine contributions to the Neurobehavioral Symptom Inventory. 59% of the variance in post-concussive symptoms were due to PTSD symptom severity while depressive symptoms and sleep problems contributed an additional 1% each. This pattern differed between those with and without clinical diagnosis of PTSD/MDD. For those with PTSD/MDD, PTSD and depression symptoms but not sleep contributed to post-concussive symptoms. For those without PTSD/MDD, PTSD symptoms and sleep contributed specifically to somatosensory post-concussive symptoms. Daytime dysfunction and sleep disturbances were associated with post-concussive symptoms after PTSD and depression symptoms were controlled. PTSD symptom severity explained the most variance for post-concussive symptoms among service members with a history of mild TBI, while depression symptoms, daytime dysfunction, and sleep disturbances independently contributed small amounts of variance.


Dynamic Kinetic Asymmetric Transformation of Racemic Diastereomers: Diastereo- and Enantioconvergent Michael-Henry Reactions to Afford Spirooxindoles Bearing Furan-Fused Rings.
Dynamic kinetic asymmetric transformation (DYKAT) reactions of racemic diastereomer mixtures that afford the products as essentially single diastereomers with high enantioselectivities are described. We demonstrated the DYKAT in the diastereo- and enantioselective synthesis of spirooxindoles bearing furan-fused rings. The starting materials of the DYKAT, dihydrobenzofuranone derivatives, were synthesized in racemic diastereomer mixtures, and these were transformed to the spirooxindole derivatives in high yields with high diastereo- and enantioselectivities through Michael-Henry cascade reactions with nitrostyrenes under organocatalytic conditions. In the reactions, regardless the stereochemistry of the starting materials, all the four isomers were transformed to single diastereomers with high enantioselectivities, and four new chiral centers were created.


Salivary gland ultrastructure and cyclic AMP-dependent reactions in Spacelab 3 rats.
Environmental stimuli influencing catecholamine levels induce changes in cyclic AMP-dependent reactions and cell morphology in the rat parotid. Responses of salivary glands to spaceflight were determined by measurement of cyclic AMP-mediated reactions in fresh-frozen salivary glands and by microscopic evaluation of ultrastructure in fixed parotid glands. Decreased cell-free protein phosphorylation occurred in parotid glands in three of five flight animals. Protein kinase activity ratios were decreased in the soluble and increased in the particulate fractions of Spacelab 3 (SL-3) rat sublingual glands, compared with ground controls. Biochemical analyses show that effects of space flight on salivary glands are similar to those induced experimentally by physiological manipulation or alteration of catecholamine levels. Morphological evaluation of three SL-3 rat parotid glands showed increased numbers of lysosomes, autophagic vacuoles containing degenerating secretory product, and accumulation of lipid droplets. Since these animals lost weight, consistent with disruption of food and water consumption, morphological changes may in part be due to decreased masticatory stimulation, as occurs with reduced food intake or a liquid diet. The observed changes may reflect physiological responses of the gastrointestinal and autonomic systems to effects of spaceflight.


Chiropractic management of postoperative spine pain: a report of 3 cases.
The purpose of this case series is to describe chiropractic care including spinal manipulation for 3 patients with postsurgical spine pain. Three patients with postsurgical spine pain (1 cervical fusion, 1 lumbar discectomy, and 1 lumbar laminectomy) presented for chiropractic treatment at a major US medical center. Treatment included spinal manipulation and/or flexion-distraction mobilization based on patient response to joint loading strategies. Two patients were treated with high-velocity, low-amplitude spinal manipulation; and 1 patient was treated with flexion-distraction mobilization. Treatment frequency and duration were 4 treatments over 4 weeks for case 1, 17 treatments over 7 years for case 2, and 5 treatments over 5 weeks for case 3. Subjective improvement was noted using numeric pain scores and functional changes; and upon completion, the patients reported being "satisfied" with their overall outcome. One episode of transient benign soreness was noted by 1 patient. No additional adverse events or effects were noted. In these 3 cases, patients with postsurgical spine pain responded positively to chiropractic care. Spinal manipulation/mobilization was tolerated without significant adverse effects.


Real-World Data on Clinical Outcomes of Patients with Liver Cancer: A Prospective Validation of the National Cancer Centre Singapore Consensus Guidelines for the Management of Hepatocellular Carcinoma.
Real-world management of patients with hepatocellular carcinoma (HCC) is crucially challenging in the current rapidly evolving clinical environment which includes the need for respecting patient preferences and autonomy. In this context, regional/national treatment guidelines nuanced to local demographics have increasing importance in guiding disease management. We report here real-world data on clinical outcomes in HCC from a validation of the Consensus Guidelines for HCC at the National Cancer Centre Singapore (NCCS). We evaluated the NCCS guidelines using prospectively collected real-world data, comparing the efficacy of treatment received using overall survival (OS) and progression-free survival (PFS). Treatment outcomes were also independently evaluated against 2 external sets of guidelines, the Barcelona Clinic Liver Cancer (BCLC) and Hong Kong Liver Cancer (HKLC). Overall treatment compliance to the NCCS guidelines was 79.2%. Superior median OS was observed in patients receiving treatment compliant with NCCS guidelines for early (nonestimable vs. 23.5 months p < 0.0001), locally advanced (28.1 vs. 22.2 months p = 0.0216) and locally advanced with macrovascular invasion (10.3 vs. 3.3 months p = 0.0013) but not for metastatic HCC (8.1 vs. 6.8 months p = 0.6300), but PFS was similar. Better clinical outcomes were seen in BCLC C patients who received treatment compliant with NCCS guidelines than in patients with treatment only allowed by BCLC guidelines (median OS 14.2 vs. 7.4 months p = 0.0002; median PFS 6.1 vs. 4.0 months p = 0.0286). Clinical outcomes were, however, similar for patients across all HKLC stages receiving NCCS-recommended treatment regardless of whether their treatment was allowed by HKLC. The high overall compliance rate and satisfactory clinical outcomes of patients managed according to the NCCS guidelines confirm its validity. This validation using real-world data considers patient and treating clinician preferences, thus providing a realistic analysis of the usefulness of the NCCS guidelines when applied in the clinics.


No association between variants in the ACE and angiotensin II receptor 1 genes and acute mountain sickness in Nepalese pilgrims to the Janai Purnima Festival at 4380 m.
Koehle, Michael S., Pei Wang, Jordan A. Guenette, and Jim L. Rupert. No association between variants in the ACE and angiotensin II receptor 1 genes and acute mountain sickness in Nepalese pilgrims to the Janai Purnima Festival at 4380 m. High Alt. Med. Biol. 7:281-289, 2006.--Acute mountain sickness (AMS) causes significant morbidity among visitors to altitude. The primary contributors to developing AMS are altitude and rate of ascent; however, the substantial variation in susceptibility between individuals has led a number of investigators to propose that there may be genetic predilection to the disease. The ACE I/D polymorphism has been shown to predict performance among elite mountaineers. This study compares genotype and allele frequencies at the ACE I/D locus, two other loci in the ACE gene, and one locus in the angiotensin-2 receptor gene between individuals who did, or did not, express signs of AMS while attending a high altitude religious festival in Nepal (4380 m). Subjects (80 males, 23 females) were recruited and genotyped. All subjects were Nepalese. Forty-four of the subjects had been diagnosed with AMS by physicians at a high altitude health camp; the rest were free from altitude illness. All subjects were genotyped at polymorphic loci in the genes encoding angiotensin converting enzyme (ACE) and angiotensin II receptor type 1 gene (AGTR1). The polymorphisms examined were two single nucleotide polymorphisms (SNPs) in ACE (ACE(A-240T), dbSNP rs4291; and ACE(A2350G), dbSNP rs4343), the intronic Alu insertion in ACE (ACE I/D), and the SNP ATR(A1166C), (dbSNP rs17231380) in AGTR1d. All polymorphisms in ACE were found to be in linkage disequilibrium. No significant associations were found between AMS incidence and any of the alleles, suggesting that variants at these loci do not contribute to susceptibility to AMS in this population.


Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles and Their Potential as Novel Immunomodulatory Therapeutic Agents.
Extracellular vesicles (EVs), such as exosomes and microvesicles, have been identified as mediators of a newly-discovered intercellular communication system. They are essential signaling mediators in various physiological and pathophysiological processes. Depending on their origin, they fulfill different functions. EVs of mesenchymal stem/stromal cells (MSCs) have been found to promote comparable therapeutic activities as MSCs themselves. In a variety of in vivo models, it has been observed that they suppress pro-inflammatory processes and reduce oxidative stress and fibrosis. By switching pro-inflammatory into tolerogenic immune responses, MSC-EVs very likely promote tissue regeneration by creating a pro-regenerative environment allowing endogenous stem and progenitor cells to successfully repair affected tissues. Accordingly, MSC-EVs provide a novel, very promising therapeutic agent, which has already been successfully applied to humans. However, the MSC-EV production process has not been standardized, yet. Indeed, a collection of different protocols has been used for the MSC-EV production, characterization and application. By focusing on kidney, heart, liver and brain injuries, we have reviewed the major outcomes of published MSC-EV in vivo studies.


British nurses in behavioural psychotherapy: a 20-year follow-up.
A postal survey was carried out of all nurse behaviour therapists trained on the English National Board for Nursing, Midwifery and Health Visiting course in adult behavioural psychotherapy (ENB 650) since its inception at Maudsley Hospital London, in 1972. All trained therapists currently in practice in the UK were surveyed, and 113 of 142 eligible respondents returned questionnaires. These were examined to elicit the professional profiles and working practices of the therapists, and to identify similarities and differences between therapists trained in the four training centres in the UK. It was found that the majority of nurse therapists remain in clinical practice after training, and continue to further their education and clinical expertise. There has been a general shift towards cognitive and short-term interventions, and towards practice based on primary care, with general practitioners providing most referrals. There were significant differences between the centres in terms of a number of the therapeutic techniques used, diagnostic categories of clients seen, and several elements of working practice, including referral source and numbers of clients seen and treated. The implications of the findings for clinical practice and for nursing in behaviour therapy are discussed.


Separation, purification, and identification of flagellin, and preparation of its antisera.
The aim of this study was to separate, purify, and identify Salmonella paratyphi A flagellin, and to prepare its antisera. Primary flagellin was isolated from S. paratyphi A using the acid lysis method. The flagellin was purified with weak anion exchange chromatography and the protein was identified with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Western blot, and negative staining with phosphotungstic acid with scanning electron microscopy (SEM). The production of the obtained flagellin was then quantified. New Zealand white rabbits were then immunized with the isolated flagellin, the presence of serum anti-flagellin antibodies was assessed with the immunoblot test, and its potency was determined with the double immunodiffusion test. The results of SDS-PAGE showed that the molecular weight (m.w.) of the purified flagellin was 52 x 10(3). The immunoblot test also showed a band at 52 x 10(3) m.w. The SEM results showed that the flagellin was filamentous. These three results showed that the protein was homogeneous. The protein quantification analysis found that 4.8 ± 0.5 mg flagellin could be extracted per 1 g wet weight bacteria. The titer of the anti-flagellin antiserum was 1:64. Through this method, we obtained high productions of flagellin, which could be easily purified, identified, and prepared into high titer antiserum.


Dynamics of capillary coalescence and breakup: Quasi-two-dimensional nematic and isotropic droplets.
We observed the formation of small satellite droplets from the bridge at droplet coalescence. Investigations were made using a Hele-Shaw cell in the two-phase region at the nematic-isotropic phase transition. In previous works on coalescence it was considered that before the start of coalescence there exists a bridge between the outer fluid connecting regions on the two sides of the droplets (outer bridge). After the start of coalescence, a bridge connecting the two droplets appears (droplet bridge) and the outer bridge is broken. We have shown that there are coalescence processes where after the start of coalescence both the droplet bridge and the outer bridge can exist. This cardinally changes the coalescence process. During the first coalescence stage the size of the outer bridge decreases and the size of the droplet bridge increases. During the second stage the outer bridge becomes unstable which leads to pinch-off, formation of pointed end domains, secondary instability, splitting of pointed end domains, and formation of satellite droplets. We found the linear dependence of the minimum bridge radius on time near bridge breakup. This behavior confirms the capillary viscous regime of bridge breakup. Our work connects two areas of fluid dynamics: coalescence and breakup with formation of satellite droplets.


Maternal parity and functional contractility of human myometrium in vitro in the third trimester of pregnancy.
It is well established that the duration of the first and second stages of labor are shorter in parous women than in their nulliparous counterparts, a phenomenon not well understood. The aim was to examine the effect of maternal parity on contractile parameters of human myometrium. Myometrial strips were excised from n = 74 women at cesarean delivery and recordings of contractile activity analyzed and compared across three clinical groups: 1. No previous delivery (P0); 2. One previous delivery (P1); 3. Greater than one previous delivery (P>1). There was a trend towards greater mean contractile force in the P>1 group than the P1 and P0 groups (P = 0.412). Frequency of contractions was less in the P1 group than in the P0 and P>1 groups(P = 0.027). No differences were observed in relation to all other parameters. Excluding frequency, no intrinsic differences were observed in the functional parameters of human uterine contractions in relation to parity.


P006 The Relationship of Histological Remission With the Duration of the Anamnesis Ulcerative Colitis.
The objectives of the treatment of patients with ulcerative colitis (UC) in accordance with the STRIDE-I provision, involves endoscopic healing of the colon mucosa. Histological remission is associated with endoscopic healing, which can be a predictor of long-term results. Biological and cellular therapy is most effective in the early stages of the disease. To assess the depth of histological remission with the duration of UC. The biopsy material of 75 patients with total or left-sided UC of moderate severity and severe severity aged from 22 to 56 years (average age 31 ± 2.5 years), who were divided into groups depending on the therapy, was studied. The first group of patients with UC aged 22 to 51 years (Me-32) (n = 29) received anti-inflammatory therapy using mesenchymal stromal cell culture (MSCs) 2 million/kg; the second group of patients with UC (n = 27) aged 24 to 56 years (Me-38) received vedolizumab (VDB) according to the recommended scheme, the third group of patients with UC (n = 19) aged 27 to 52 years (Me-31) received MSCs+VDB. The achievement of histological remission was assessed by the score of Geboes (SG). In 1st group, patients who achieved histological remission (SG1) with a disease duration of more than 5 years - 14 (48.3%) patients, less than 5 years - 5 (17.2%) (95% CI 1.256 - 19.293; x2-7.635; p = 0.006). In the 2nd group of patients who achieved histological remission (SG1) with a disease duration of more than 5 years - 15 (55.5%) patients, less than 5 years - 4 (14.9%) (95% CI 1.262 - 20.615; x2-7.026; p = 0.009). In the 3rd group of patients who achieved histological remission (SG1) with a disease duration of more than 5 years - 4 (21.1%) patients, less than 5 years - 7 (36.8%) (95% CI 1.080 - 138.995; x2-4.968; p = 0.026). A statistically significant majority of patients who achieved histological remission, regardless of the therapy, had a disease duration of less than 5 years.


Renal vein dilation predicts poor outcome in patients with refractory cirrhotic ascites.
Renal venous hypertension is known to be associated with worsening of renal function in patients with decompensated heart failure. Intra-abdominal hypertension including cirrhotic ascites also leads to renal venous hypertension. We aimed to clarify the effect of renal venous hypertension on cirrhotic ascites. Two hepatologists measured the left renal vein diameter in 142 consecutive patients with refractory cirrhotic ascites using non-contrast computed tomography. The renal vein diameter was measured at the renal vein main trunk and upstream of the confluence of collateral veins. The inter-observer agreements were high for the measurements of the left renal vein (r = 0.918, P < 0.001). The median overall survival for patients with renal vein diameter ≥11 mm was less than that for patients with renal vein diameter <11 mm (P < 0.001; 2.5 vs. 32.0 months). One-year survival rates were 15.3% versus 66.4%. Multivariate analysis revealed renal vein diameter ≥11 mm (hazard ratio, 2.94; P < 0.001; 95% confidence interval, 1.67-5.20) and a high Model for End-stage Liver Disease score combined with serum sodium level (MELD-Na) (hazard ratio, 3.39; P < 0.001; 95% confidence interval, 2.00-5.74) were significant independent predictors of mortality. Renal vein dilation is a risk factor of mortality in patients with refractory cirrhotic ascites, independent of the MELD-Na score.


HYBRID BREAKDOWN IN PHYSIOLOGICAL RESPONSE: A MECHANISTIC APPROACH.
Data comparing the physiological response to hyperosmotic stress in individual copepods (Tigriopus californicus) from natural populations and laboratory hybrids are presented. While individuals from two genetically differentiated natural populations and F1 interpopulation hybrids showed only minor differences in patterns of free amino acid (FAA) accumulation during hyperosmotic stress, patterns of FAA synthesis were highly variable among the F2 hybrids. Isofemale lines initiated from later hybrid generations (F7 -F10 ) exhibited substantial inter-line variance in FAA accumulation. This increased variance in physiological response appears unrelated to allozyme polymorphisms at two loci encoding FAA-metabolizing enzymes and appears to result from other, unidentified polymorphisms in the proline synthetic pathway.


Intraoperative hypotension - a neglected causative factor in hospital-acquired acute kidney injury; a Mayo Clinic Health System experience revisited.
Acute kidney injury (AKI) is a relatively common complication of cardiothoracic surgery and has both short- and long-term survival implications, even when AKI does not progress to severe renal failure. Given that currently, there are no active effective treatments for AKI, other than renal replacement therapy when indicated, the focus of clinicians ought to be on prevention and risk factor management. In the AKI-surgery literature, there exists this general consensus that intraoperative hypotension (IH) following hypotensive anesthesia (HA) or controlled hypotension (CH) in the operating room has no significant short-term and long-term impacts on renal function. In this review, we examine the basis for this consensus, exposing some of the flaws of the clinical study data upon which this prevailing consensus is based. We then describe our experiences in the last decade at the Mayo Clinic Health System, Eau Claire, in Northwestern Wisconsin, USA, with two selected case presentations to highlight the contribution of IH as a potent yet preventable cause of post-operative AKI. We further highlight the causative although neglected role of IH in precipitating postoperative AKI in chronic kidney disease (CKD) patients. We show additional risk factors associated with this syndrome and further make a strong case for the elimination of IH as an achievable mechanism to reduce overall, the incidence of hospital acquired AKI. We finally posit that as the old saying goes, prevention is indeed better than cure.


Understanding adverse drug-related emergency department visits: development of a conceptual model through a systematic review.
The burden of adverse drug event (ADE)-related emergency department (ED) visits is increasing despite several preventive measures. The objective of this paper was to develop and validate a conceptual model for a better understanding of ADE-related ED visits and to guide the design and implementation of effective interventions. The development of the model involved a systematic review of the literature using PubMed and Embase databases. Studies reporting the risk factors associated with ADE-related ED visits were included. The methodological qualities of the included studies were assessed using the Mixed Methods Appraisal Tool (MMAT). The model was mapped and validated using face and content validity by an expert panel. Deficiencies and targeted interventions were identified, and steps for the design and implementation were recommended. The literature search generated 1361 articles, of which 38 were included in the review; 41 risk factors associated with ADE-related ED visits were identified. All factors were mapped, and the model was validated through face and content validity. The model consisted of six concepts related to sociodemographic factors, clinical factors, ADE-related to ED visits, ADE while in the ED, outcomes, and consequences. Interventions could be targeted at the factors identified in each concept to prevent ADE-related ED burden. A conceptual model to guide the successful design and implementation of strategies to prevent ADE-related ED visits and the occurrence of ADE at ED was developed. Clinicians should take these factors into consideration to prevent untoward events, especially when treating high-risk patients.


Accidental avulsion of a recently traumatised maxillary anterior tooth during rubber dam application.
Avulsion injuries are usually seen in the anterior maxillary teeth as a result of trauma. Avulsion as an endodontic mishap is extremely rare. This report highlights an unusual instance of exarticulation of a recently traumatised maxillary central incisor tooth when the rubber dam was applied during a routine non-surgical endodontic procedure. The tooth was immediately repositioned and stabilised with wire composite splint. Endodontic treatment was initiated after rubber dam isolation with a modified technique. Calcium hydroxide was used as intracanal medicament dressing, and obturation was done after 2 weeks. The treatment was successful with uneventful periodontal healing at 24-month follow-up. The presence of well-demarcated periodontal ligament space and absence of any resorptive area on the radiograph could be defined as a successful outcome for the present case.


A prospective study of diagnostic epidural blockade in the assessment of chronic back and leg pain.
A consecutive series of 100 patients with back and leg pain were evaluated prospectively. All had a detailed clinical assessment together with radiculography and computed tomography (CT) of the lumbosacral spine. In addition, each patient underwent diagnostic epidural blockade that identified three kinds of response. Injection of local anaesthetic into the epidural space relieved the symptomatic pain--the positive result (51 patients). Local anaesthetic injection had no effect on the symptomatic pain--the negative result (30 patients). In 19 patients, saline injection into the epidural space relieved the symptomatic pain--the placebo result. The results of this investigation were assessed in the light of the number of inappropriate physical signs found on clinical examination, together with the result of the radiculogram and CT scan. No statistical correlation was found with any of these parameters.


Just hypercalcaemia or acute ST elevation myocardial infarction? A review of hypercalcaemia-related electrocardiographic changes.
In elderly patients presenting with confusion and recurrent falls, conditions including infection, acute stroke, acute coronary events and electrolyte abnormalities have to be strongly considered as diagnostic possibilities. ECG is a non-invasive test that often serves as a useful tool in suggesting the underlying electrolyte disturbance. However, ECG must be interpreted with caution as it can, at times, be misleading, as in this case of hypercalcaemia seen by us. We discuss the different ECG findings in hypercalcaemic situations.


Effects of carocainide (770207) on canine cardiac automaticity.
The benzofuran derivative carocainide is a new class I antiarrhythmic drug which has been shown to prevent and stop experimental ventricular arrhythmias. The effects of this drug on different types of cardiac automaticity were investigated by experimental models using "in situ" dogs' hearts. Complete A-V block was produced by local formaldehyde injection into the A-V junction. Carocainide at doses of 2.5, 5 and 7.5 mg/kg body weight i.v. produced the following effects: a significant and dose-related slowing of the idioventricular rate; a non-significant change of the sinus rate at 2.5 and 5 mg/kg b.w.; and a significant decrease of the total number of triggered ventricular beats induced by ventricular pacing during slow norepinephrine infusion. Our results suggest that carocainide could be a safe and effective drug for the treatment of ventricular arrhythmias.


Silencing of hypoxia-inducible tumor suppressor lysyl oxidase gene by promoter methylation activates carbonic anhydrase IX in nasopharyngeal carcinoma.
Lysyl oxidase (LOX) is an oxidative enzyme known to initiate the cross-linking of collagens and elastin, and suggested recently as a tumor suppressor for several tumor types including lung, pancreatic and gastric cancers. Previously we showed that LOX is strongly induced upon hypoxia in nasopharyngeal carcinoma (NPC) cell lines CNE2 and HONE1 but only slightly in HK1 and not in C666-1. Here, we further studied the regulatory mechanism and functions of LOX in NPC. LOX is widely expressed in human normal tissues with variations in expression levels. LOX was expressed in most NPC cell lines except for C666-1, while HK1 and FaDu (laryngeal cancer) only expressed low level of LOX. Methylation analysis showed that the LOX promoter was methylated in C666-1 and partially methylated in HK1. After demethylation with 5-aza-2'-deoxycytidine, LOX expression was reactivated along with increased unmethylated alleles. LOX promoter methylation was detected in 42/49 (85.7%) of NPC primary tumors but only 3/16 (18.75%) of nose swab samples from NPC patients. LOX overexpression reduced the clonogenicity and cell growth of NPC cells, and also inhibited the migration and invasion of the NPC cells. Carbonic anhydrase IX (CA9) mRNA level was obviously decreased in HK1 cells after transfection with LOX. The elevation of CA9 protein upon hypoxia was inhibited in LOX-transfected HK1 cells. The protein levels of an apoptosis marker cPARP were increased in LOX-transfected HK1 cells upon hypoxia treatment. Our data showed that silencing or down-regulation of LOX in NPC was due to its promoter methylation and LOX acts as a tumor suppressor in NPC. LOX silencing would facilitate NPC cells to escape from hypoxia-induced apoptosis and maintains a malignant and metastatic phenotype.


Amniotic Fluid Embolism.
We report a case of 34-year patient who had uncomplicated elective caesarean-section. Postoperatively, she developed sudden hypotension, bradycardia, dyspnea and disseminated intravascular coagulation (DIC), all signs associated with amniotic fluid embolism (AFE). Echocardiogram showed signs of acutely increased right ventricular after load including McConell's sign, i.e. right ventricular dilatation, segmental hypokinesia (mid-right ventricular) and hypercontractile right ventricular apex and overall right ventricular dysfunction. Similarly, 60/60 sign was positive on chocardiography (decreased right ventricular acceleration time of less than 60 milli-seconds and pulmonary artery systolic pressure of less than 60 mmHg). Performance of CT pulmonary angiogram failed to show any clear thromboembolic phenomenon; although, there were other indirect signs pointing towards the diagnosis. She was treated with aggressive supportive care without anticoagulation and she showed complete recovery, with follow-up echocardiogram becoming absolutely normal after 9 days with normalization of right ventricular size and function and improvement in 60/60 sign.


[Adequate correction of gastric functional structure in surgery of peptic ulcer].
Self-regulating mechanisms of homeostasis of the digestive apparatus are interrelated and interdependent with the algorithm of alimentary chymus movement from stomach into bowels. As the natural digestive tract is disturbed (pylorectomy, shutting-off the duodenum and drainage of stomach), the pathology leaves the frameworks of one organ and takes on a polyorgan character. A new principle of operation--adequate correction of functional structures of stomach ("repair" of the organ)--is suggested. It is based on the original plastic surgery of the pyloric canal, which enables us to maintain the natural algorithm of the gastroduodenal "passage", ulcerectomy and correction of acid formation. The status of regulating systems was estimated by the vital activity of the mucous membrane of the operated stomach, the trophism of which depends on the total influence of "feedbacks", as has been known.


Differential effects of leukotactin-1 and macrophage inflammatory protein-1 alpha on neutrophils mediated by CCR1.
The human CC chemokine leukotactin-1 (Lkn-1) is both a strong chemoattractant for neutrophils, monocytes, and lymphocytes and a potent agonist for CCR1 and CCR3. However, human neutrophils do not migrate when the cells are stimulated with other human CC chemokines, such as human macrophage inflammatory protein-1 alpha (hMIP-1 alpha) and eotaxin, which also use the CCR1 and CCR3 as their receptors. In this report, we demonstrate that while hMIP-1 alpha induced a negligible level of calcium flux and chemotaxis, Lkn-1 produced a high level of calcium flux and chemotaxis in human neutrophils. Lkn-1 cross-desensitized hMIP-1 alpha-induced calcium flux, but hMIP-1 alpha had little effect on the Lkn-1-induced response in human neutrophils. The same pattern was observed in peritoneal neutrophils from wild-type mice, whereas neutrophils from CCR1-/- mice failed to respond to either MIP-1 alpha or Lkn-1. Scatchard analysis revealed a single class of receptor for both hMIP-1 alpha and Lkn-1 on human neutrophils with dissociation constants (Kd) of 3.2 nM and 1.1 nM, respectively. We conclude that CCR1 is a receptor mediating responses to both MIP-1 alpha and Lkn-1 on neutrophils and produces different biological responses depending on the ligand bound.


Tunneling electroresistance in multiferroic heterostructures.
We demonstrate the room temperature polar switching and tunneling in PbZr0.52Ti0.48O3 (PZT) ultra-thin films of thickness 3-7 nm, sandwiched between platinum metal and ferromagnetic La0.67Sr0.33MnO3 (LSMO) layers, which also shows magnetic field dependent tunnel current switching in Pt/PbZr0.52Ti0.48O3/La0.67Sr0.33MnO3 heterostructures. The epitaxial nature, surface quality and ferroelectric switching of heterostructured films were examined with the help of x-ray diffraction patterns, atomic force microscopy, and piezo force microscopy, respectively. The capacitance versus voltage graphs show butterfly loops above the coercive field (> ±3 V) of PZT for small probe area (∼16 μm(2)). The effect of ferroelectric switching was observed in current density versus voltage curves with a large variation in high-resistance/low-resistance (HRS/LRS) ratio (2:1 to 100:1), however, these effects were more prominent in the presence of in-plane external magnetic field. The conductance is fitted with Brinkman's model, and the parabolic conductance upon bias voltage implies electron tunneling governs the transport.


Isolation and characterization of thymitaq (AG337) and 5-fluoro-2-deoxyuridylate-resistant mutants of human thymidylate synthase from ethyl methanesulfonate-exposed human sarcoma HT1080 cells.
Thymidylate synthase plays an essential role in the synthesis of DNA. Recently, several new and specific thymidylate synthase inhibitors that occupy the folate binding site, including Tomudex(R), BW1843U89, and Thymitaq, have demonstrated therapeutic activity in patients with advanced cancer. In order to find drug-resistant forms of human thymidylate synthase for gene therapy applications, human sarcoma HT1080 cells were exposed to ethyl methanesulfonate and Thymitaq selection. Thymitaq-resistant clonal derived sublines were established, and analysis indicated that both gene amplification and point mutations contributed to drug resistance. Eight mutant cDNAs that were identified from Thymitaq-resistant sublines were generated by site-directed mutagenesis and transfected into thymidylate synthase-negative cells. Only K47E, D49G, or G52S mutants retain enzyme activity. Moreover, cytotoxicity studies demonstrated that D49G and G52S transfected cells, besides displaying resistance to Thymitaq with IC50 values 40- and 12-fold greater than wild-type enzyme transfected cells, respectively, also lead to fluorodeoxyuridine resistance (26- and 97-fold in IC50 values, respectively) but not to Tomudex or BW1843U89. Characterization of the purified altered enzymes obtained from expression in Escherichia coli is consistent with the cell growth inhibition results. We postulate that the D49G or G52S mutation leads to the structural perturbation of the highly conserved Arg50 loop, decreasing the binding of thymidylate synthase to the inhibitors, Thymitaq and fluorodeoxyuridylate.


Chemoradiotherapy in geriatric patients with squamous cell carcinoma of the esophagus: Multi-center analysis on the value of standard treatment in the elderly.
To evaluate the tolerability and outcomes of chemoradiation in elderly patients with locally advanced esophageal squamous cell carcinoma (ESCC). This multi-center retrospective analysis included 161 patients with SCC of the esophagus with a median age of 73 years (range 65-89 years) treated with definitive or neoadjuvant (chemo)radiotherapy between 2010 and 2019 at 3 large comprehensive cancer centers in Germany. Locoregional control (LRC), progression-free survival (PFS), distant metastasis-free survival (DMFS), overall survival (OS), and treatment-associated toxicities were analyzed, and parameters determining patient outcomes and treatment tolerance were assessed. The delivery of radiotherapy without dose reduction was possible in 149 patients (93%). In 134 patients (83%), concomitant chemotherapy was initially prescribed; however, during the course of therapy, 41% of these patients (n = 55) required chemotherapy de-escalation due to treatment-related toxicities. Fifty-two patients (32%) experienced higher-grade acute toxicities, and 22 patients (14%) higher-grade late toxicities. The 2-year LRC, DMFS, PFS, and OS rates amounted to 67.5%, 33.8%, 31.4%, and 40.4%, respectively. Upon multivariate analysis, full-dose concomitant chemotherapy (vs. no or modified chemotherapy) was associated with significantly better DMFS (p=0.005), PFS (p=0.005) and OS (p=0.001). Furthermore, neoadjuvant chemoradiotherapy followed by tumor resection (vs. definitive chemoradiotherapy or definitive radiotherapy alone) significantly improved PFS (p=0.043) and OS (p=0.049). We could not identify any clinico-pathological factor that was significantly associated with LRC. Furthermore, definitive (chemo)radiotherapy, brachytherapy boost and stent implantation were significantly associated with higher-grade acute toxicities (p<0.001, p=0.002 and p=0.04, respectively). The incidence of higher-grade late toxicities was also significantly associated with the choice of therapy, with a higher risk for late toxicities when treatment was switched from neoadjuvant to definitive (chemo)radiotherapy compared to primary definitive (chemo)radiotherapy (p<0.001). Chemoradiation with full-dose and unmodified concurrent chemotherapy has a favorable prognostic impact in elderly ESCC patients; however, about half of the analyzed patients required omission or adjustment of chemotherapy due to comorbidities or toxicities. Therefore, the identification of potential predictive factors for safe administration of concurrent chemotherapy in elderly ESCC patients requires further exploration to optimize treatment in this vulnerable patient cohort.


Characterization of a new Agrobacterium tumefaciens strain from alfalfa.
Agrobacterium tumefaciens strain 1D1609 is reported here as the first field isolate from alfalfa (Medicago sativa L.). Unlike well-characterized A. tumefaciens strains such as C58 and Ach5, strain 1D1609 is highly virulent on alfalfa and has a distinctive host range. Interestingly, strain 1D1609 is naturally resistant to kanamycin and spectinomycin. The Ti plasmid in strain 1D1609 is an octopine-type; thus, tumors formed by strain 1D1609 synthesize octopine, which is utilized by the bacterium as a sole carbon source. Reciprocal exchange of Ti plasmids between strains 1D1609 and C58 showed that both chromosomal and Ti plasmid genes in strain 1D1609 contribute specifically to tumor formation on alfalfa. In addition, the nondormant CUF101 alfalfa cultivar from which strain 1D1609 was isolated was significantly more susceptible to all Agrobacterium strains tested than was the dormant Agate cultivar.


The Neuropsychiatric Inventory: assessing psychopathology in dementia patients.
The Neuropsychiatric Inventory (NPI) was developed to assess psychopathology in dementia patients. It evaluates 12 neuropsychiatric disturbances common in dementia: delusions, hallucinations, agitation, dysphoria, anxiety, apathy, irritability, euphoria, disinhibition, aberrant motor behavior, night-time behavior disturbances, and appetite and eating abnormalities. The severity and frequency of each neuropsychiatric symptom are rated on the basis of scripted questions administered to the patient's caregiver. The NPI also assesses the amount of caregiver distress engendered by each of the neuropsychiatric disorders. A total NPI score and a total caregiver distress score are calculated, in addition to the scores for the individual symptom domains. Content validity, concurrent validity, inter-rater reliability, and test-retest reliability of the NPI are established. Different neurologic disorders have characteristic neuropsychiatric manifestations and distinctive NPI profiles. The NPI is sensitive to treatment effects and has demonstrated the amelioration of behavioral symptoms in Alzheimer's disease by cholinergic agents. The NPI is a useful instrument for characterizing the psychopathology of dementia syndromes, investigating the neurobiology of brain disorders with neuropsychiatric manifestations, distinguishing among different dementia syndromes, and assessing the efficacy of treatment.


Vitiligo: Not Simply a Skin Disease.
Melanocytes, the cells responsible for skin pigmentation, are present in other parts of the body, such as the ocular, auditory, nervous, and cardiac systems. Within these systems, their roles serve a different purpose than their classical counterparts in skin as pigment cells. Such roles include cell turnover in retinal pigment epithelium, maintenance of balance and prevention of environmental damage in the auditory neuroepithelium, role-playing as dendritic cells within the leptomeninges, and prevention of oxidative damage in adipose tissue. Vitiligo, commonly known as a skin pigmentation disorder, has also been associated with several systemic disorders, such as Vogt-Koyanagi-Harada disease and Alezzandrini, Kabuki, and MELAS syndromes. Therefore, since these conditions involve compromise of systems in which melanocytes reside, it is not surprising that vitiligo has other systemic associations. The authors present a detailed review of systemic associations of vitiligo and melanocytes' roles in other organ systems with a focus on systemic disease.


Modulation of CaM kinase II activity is coincident with induction of status epilepticus in the rat pilocarpine model.
This study was conducted to characterize the early cellular changes in CaM kinase II activity that occur during the induction of status epilepticus (SE). The pilocarpine model of SE was characterized both behaviorally and electrographically. At specific time points after the first discrete seizure, specific brain regions were isolated for biochemical study. Phosphate incorporation into a CaM kinase II-specific substrate, autocamtide III, was used to determine kinase activity. After the development of SE, the data show an immediate inhibition of both cortical and hippocampal CaM kinase II activity in homogenate, but a delayed inhibition in synaptic kinase activity. The maintenance of synaptic kinase activity was due to a translocation of CaM kinase II protein to the synapse. However, despite the translocation of functional kinase, CaM kinase II activity was not maintained, membrane potential was not restored, and the newly translocated CaM kinase II did not terminate the SE event. Unlike the homogenate samples, in the crude synaptoplasmic membrane (SPM) subcellular fractions, a positive correlation is found between the duration of SE and the inhibition of CaM kinase II activity in both the cortex and hippocampus. The data support the hypothesis that alterations of CaM kinase II activity are involved in the early events of SE pathology.


Acute myelomonocytic leukemia after treatment with chronic oral etoposide: are MLL and LTG9 genes targets for etoposide?
A patient with secondary acute myelomonocytic leukemia after treatment with chronic oral etoposide (VP-16) for lung cancer is reported. The leukemic cells showed a t(9;11)(p22;q23) translocation. Southern blot analysis revealed the rearrangement of the MLL (ALL-1/HRX) gene at 11q23. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed a chimeric mRNA between the MLL gene at 11q23 and LTG9 (MLLT3/AF-9) gene at 9p22. The patient was successfully treated with a VP-16 based regimen. This case is instructive in the understanding of the leukemogenesis of VP-16-related leukemias.


Thermally induced local failures in quasi-one-dimensional systems: collapse in carbon nanotubes, necking in nanowires, and opening of bubbles in DNA.
We present a general framework to explore thermally activated failures in quasi-one-dimensional systems. We apply it to the collapse of carbon nanotubes, the formation of bottlenecks in nanowires, both of which affect conductance, and the opening of local regions or "bubbles" of base pairs in strands of DNA that are relevant for transcription and denaturation. We predict an exponential behavior for the probability of the opening of bubbles in DNA, the average distance between flattened regions of a nanotube or necking in a nanowire as a monotonically decreasing function of temperature, and compute a temperature below which these events become extremely rare.


Genomic evolution and phenotypic distinctions of Chikungunya viruses causing the Indian Ocean outbreak.
In our current global community with the rapid movement of products and people across and between continents, the emergence of a human pathogen can have devastating consequences. One dramatic example of this has been the emergence of Chikungunya virus (CHIKV), which causes a severe, prolonged, and debilitating arthralgic disease. This virus emerged in a large outbreak on the east coast of Africa in 2004; over the subsequent seven years, CHIKV has spread across the Indian Ocean, the Indian subcontinent, Southeast Asia and even reached Europe, leaving more than two million people affected. Because CHIKV has a small genome, currently available tools to analyze complete viral genomes have provided scientists with unique opportunities to understand the epidemiology, pathogenesis and transmission of the virus. The most commonly used application of these cutting edge tools has been to track the movement of the virus over time and space. While this is an important concept for identifying areas that remain at risk for outbreaks, these postgenomic era tools can also be applied to the highly significant tasks of understanding how viral microevolutionary changes can affect both invertebrate transmission and vertebrate virulence. Significant alterations in the patterns of CHIKV movement have already been identified using microevolutionary studies. These approaches now need to be further expanded to aid in expanding vaccine, therapeutic and control options. This review will highlight some of the most significant recent research developments obtained using these cutting edge approaches for CHIKV.


Advances in the cellular and molecular biology of the beta-amyloid protein in Alzheimer's disease.
Alzheimer's disease (AD) is a progressive senile dementia characterized by deposition of a 4 kDa peptide of 39-42 residues known as amyloid beta-peptide (Abeta) in the form of senile plaques and the microtubule associated protein tau as paired helical filaments. Genetic studies have identified mutations in the Abeta precursor protein (APP) as the key triggers for the pathogenesis of AD. Other genes such as presenilins 1 and 2 (PS1/2) and apolipoprotein E (APOE) also play a critical role in increased Abeta deposition. Several biochemical and molecular studies using transfected cells and transgenic animals point to mechanisms by which Abeta is generated and aggregated to trigger the neurodegeneration that may cause AD. Three important enzymes collectively known as "secretases" participate in APP processing. An enzymatic activity, beta-secretase, cleaves APP on the amino side of Abeta producing a large secreted derivative, sAPPbeta, and an Abeta-bearing membrane-associated C-terminal derivative, CTFbeta, which is subsequently cleaved by the second activity, gamma-secretase, to release Abeta. Alternatively, a third activity, alpha-secretase, cleaves APP within Abeta to the secreted derivative sAPPalpha and membrane-associated CTFalpha. The predominant secreted APP derivative is sAPPalpha in most cell-types. Most of the secreted Abeta is 40 residues long (Abeta40) although a small percentage is 42 residues in length (Abeta42). However, the longer Abeta42 aggregates more readily and was therefore considered to be the pathologically important form. Advances in our understanding of APP processing, trafficking, and turnover will pave the way for better drug discovery for the eventual treatment of AD. In addition, APP gene regulation and its interaction with other proteins may provide useful drug targets for AD. The emerging knowledge related to the normal function of APP will help in determining whether or not the AD associated changes in APP metabolism affect its function. The present review summarizes our current understanding of APP metabolism and function and their relationship to other proteins involved in AD.


Parametric Modeling of Human Gradient Walking for Predicting Minimum Energy Expenditure.
A mathematical model to predict the optimum gradient for a minimum energetic cost is proposed, based on previous results that showed a minimum energetic cost when gradient is -10%. The model focuses on the variation in mechanical energy during gradient walking. It is shown that kinetic energy plays a marginal role in low speed gradient walking. Therefore, the model considers only potential energy. A mathematical parameter that depends on step length was introduced, showing that the optimal gradient is a function of that parameter. Consequently, the optimal negative gradient depends on the individual step length. The model explains why recent results do not suggest a single optimal gradient but rather a range around -10%.


Synthesis and biological evaluation of some new substituted naphthoquinones.
Two novel series of 1,4-naphthoquinone derivatives have been synthesized namely; N-ethoxycarbonyl-2-ethoxycarbonyloxy-3- alkyl-1,4-naphthoquinon-1-substituted phenylhydrazones 3a-f and 2-chlorocetyloxy-3-alkyl-1,4-naphthoquinone-1-substituted phenylhydrazones 4a-d. The antimicrobial activity as well as anticancer activity of these compounds have been evaluated. The acute toxicity of the active compounds was determined.


Novel long-term immobilization method for radioactive iodine-129 using a zeolite/apatite composite sintered body.
The amount of radioactive iodine generated from nuclear power plants is expected to increase with the proliferation of nuclear energy production, and long-term immobilization methods for such radioactive elements need to be developed to make nuclear energy sustainable. The standard immobilization method of radioactive elements, vitrification, is not very effective for radioactive iodine-129 because of the low solubility of iodine in silicate melts, its very high volatility at standard vitrification process temperatures, and its instability in the alkaline environment of deep geological layers below 300 m. We have developed a novel three-phase ceramic composite produced by a sintering process. Iodine adsorbed onto Ca-type zeolite A was covered with a hydroxyapatite nanolayer through the exchange reaction of ammonium with calcium. Clusters of iodine of 30 nm within the zeolite structure were found to be thermally stable up to 1253 K because of the partial blockage of the alpha-cage apertures by ammonium ions and the partial change from a crystalline phase to an amorphous phase at 473 K. No gasification of iodine molecules was found to occur during the sintering process. The outer phase was highly crystalline hydroxyfluorapatite in which the hydroxyapatite nanolayer plays an important role for successful sintering. The elution of iodine in low-dioxygen water, similar to that found within the Earth's crust, was investigated and was found to occur only in the surface layer of the sintered body.


High resolution optical mapping of cardiac electrophysiology in pre-clinical models.
Optical mapping of animal models is a widely used technique in pre-clinical cardiac research. It has several advantages over other methods, including higher spatial resolution, contactless recording and direct visualisation of action potentials and calcium transients. Optical mapping enables simultaneous study of action potential and calcium transient morphology, conduction dynamics, regional heterogeneity, restitution and arrhythmogenesis. In this dataset, we have optically mapped Langendorff perfused isolated whole hearts (mouse and guinea pig) and superfused isolated atria (mouse). Raw datasets (consisting of over 400 files) can be combined with open-source software for processing and analysis. We have generated a comprehensive post-processed dataset characterising the baseline cardiac electrophysiology in these widely used pre-clinical models. This dataset also provides reference information detailing the effect of heart rate, clinically used anti-arrhythmic drugs, ischaemia-reperfusion and sympathetic nervous stimulation on cardiac electrophysiology. The effects of these interventions can be studied in a global or regional manner, enabling new insights into the prevention and initiation of arrhythmia.


Assessment of the sedative effects of dexmedetomidine, an alpha 2-adrenoceptor agonist, with analysis of saccadic eye movements.
Single intravenous doses (0.5 microgram/kg and 1.0 microgram kg) of dexmedetomidine (4(5)-(1-(2,3-dimethylphenyl)ethyl)imidazole), a selective alpha 2-adrenoceptor agonist, and saline placebo were administered to six healthy volunteers (4 males and 2 females) in a double-blind, placebo-controlled cross-over study. The effects on vigilance were assessed using both subjective estimation (visual analogue scale, VAS) and objective tests (critical flicker fusion frequency, CFF; the Maddox wing; saccadic eye movement analysis). Dose-dependent subjective sedation was seen in VAS measurements, and impairment of vigilance was observed in CFF, Maddox wing and peak saccadic velocity, while saccade latency was not influenced by dexmedetomidine. The changes in vigilance were concurrent with moderate reductions in blood pressure and heart rate. CFF, the Maddox wing and peak saccadic velocity all proved sensitive in the assessment of sedation induced by dexmedetomidine.


Factors affecting the outcome of corneal transplantation.
Corneal grafting has been attempted for 200 years. Greatly improved results in recent years have been attributed to developments in anaesthesia, asepsis, and immunological and anti-inflammatory therapy. The important factors affecting the outcome of corneal grafting today are the degree of vascularisation of the cornea before surgery, the inflammatory status at the time of surgery, and the number of antigenic determinants shared by donor and host. Allograft rejection is the most common cause of corneal graft failure. Animal experiments suggest that cyclosporin A given at the time of surgery is likely to prove the most effective means available for preventing corneal graft rejection. Although the introduction of more specific immunosuppressive agents is important, the development of techniques to improve the environment of the outer eye demands the highest priority. Corneal disease is the commonest cause of blindness on a world scale, but many patients are unacceptable for grafting with the currently accepted criteria for operability.


Response in individuals with and without foreign background and application to the National Cohort in Germany: which factors have an effect?
Response rates in epidemiologic studies vary widely. This study examines response rates of potential study participants according to foreign versus German background and investigates effects of recruitment strategies. Response rates and characteristics of recruitment procedures from feasibility studies for a large cohort study conducted in 2011 were analyzed. Among 1,235 participants the proportion of recruited individuals with a foreign background was 17.3% (95% confidence interval 15.3-19.5%), significantly lower than in the sampling frame (23.1%). The difference between observed and expected proportion was high among individuals with Turkish background and smaller among ethnic Germans from the Former Soviet Union and other foreign background groups. Common recruitment strategies to increase the response had positive effects in all groups. For the planned recruitment strategy in the forthcoming German National Cohort, we estimate an overall response of approximately 50%. Individuals with Turkish background may need particular efforts to be adequately represented in a population-based cohort in Germany. Other foreign background groups are relatively well represented using standard procedures. An adequate response can be obtained under carefully planned recruitment strategies.


Nuclear Factor I-C acts as a regulator of hepatocyte proliferation at the onset of liver regeneration.
Knockout studies of the murine Nuclear Factor I-C (NFI-C) transcription factor revealed abnormal skin wound healing and growth of its appendages, suggesting a role in controlling cell proliferation in adult regenerative processes. Liver regeneration following partial hepatectomy (PH) is a well-established regenerative model whereby changes elicited in hepatocytes lead to their rapid and phased proliferation. Although NFI-C is highly expressed in the liver, no hepatic function was yet established for this transcription factor. This study aimed to determine whether NFI-C may play a role in hepatocyte proliferation and liver regeneration. Liver regeneration and cell proliferation pathways following two-thirds PH were investigated in NFI-C knockout (ko) and wild-type (wt) mice. We show that the absence of NFI-C impaired hepatocyte proliferation because of plasminogen activator I (PAI-1) overexpression and the subsequent suppression of urokinase plasminogen activator (uPA) activity and hepatocyte growth factor (HGF) signalling, a potent hepatocyte mitogen. This indicated that NFI-C first acts to promote hepatocyte proliferation at the onset of liver regeneration in wt mice. The subsequent transient down regulation of NFI-C, as can be explained by a self-regulatory feedback loop with transforming growth factor beta 1 (TGF-ß1), may limit the number of hepatocytes entering the first wave of cell division and/or prevent late initiations of mitosis. NFI-C acts as a regulator of the phased hepatocyte proliferation during liver regeneration.


Differential charge sensing and charge delocalization in a tunable double quantum dot.
We report measurements of a tunable double quantum dot, operating in the quantum regime, with integrated local charge sensors. The spatial resolution of the sensors allows the charge distribution within the double dot system to be resolved at fixed total charge. We use this readout scheme to investigate charge delocalization as a function of temperature and strength of tunnel coupling, demonstrating that local charge sensing can be used to accurately determine the interdot coupling in the absence of transport.


Corrugated-Diaphragm Based Fiber Laser Hydrophone with Sub-100 μPa/Hz1/2 Resolution.
In this work, a beat-frequency encoded fiber laser hydrophone is developed for high-resolution acoustic detection by using an elastic corrugated diaphragm. The diaphragm is center-supported by the fiber. Incident acoustic waves deform the diaphragm and induce a concentrated lateral load on the laser cavity. The acoustically induced perturbation changes local optical phases and frequency-modulates the radio-frequency beat signal between two orthogonal lasing modes of the cavity. Theoretical analysis reveals that a higher corrugation-depth/thickness ratio or larger diaphragm area can provide higher transduction efficiency. The experimentally achieved average sensitivity in beat-frequency variation is 185.7 kHz/Pa over a bandwidth of 1 kHz. The detection capability can be enhanced by shortening the cavity length to enhance the signal-to-noise ratio. The minimum detectable acoustic pressure reaches 74 µPa/Hz1/2 at 1 kHz, which is comparable to the zeroth order sea noise.


Improvement in knowledge of healthcare professionals attending Neonatal Life Support (NeoLiS) training workshop.
To assess the improvement in knowledge of healthcare professionals after attending Neonatal Life Support training workshop. The interventional study with secondary data was conducted in the Neonatology Department of the Children's Hospital and the Institute of Child Health, Lahore, Pakistan, using 2-year data of all the training workshops from 2017 to 2018. The participants were consultants, post-graduate residents, nurses, lady health visitors, lady health workers and rescue workers. Knowledge was tested through a true/false questionnaire regarding resuscitation skills both before and after the hands-on workshop. The score of each candidate was recorded on a results sheet. Baselines scores were compared with respective post-workshop test. Data was analysed using SPSS 20. Of the 52 workshops, 35(%) were conducted in 2017 and 17(%)in 2018, and of the 1350 particpants, 1080(81%) were doctors, 257(18%) were nurses and 13(1%) were paramedics and rescue workers. Mean overall baseline score was 71.96±8.38 compared to 86.60+/-5.48 post-intervention (p<0.001). The Neonatal Life Support training workshop resulted in significant gain in knowledge about neonatal resuscitation by healthcare professionals.


Xanthine oxidase inhibition protects against Western diet-induced aortic stiffness and impaired vasorelaxation in female mice.
Consumption of a high-fat, high-fructose diet [Western diet (WD)] promotes vascular stiffness, a critical factor in the development of cardiovascular disease (CVD). Obese and diabetic women exhibit greater arterial stiffness than men, which contributes to the increased incidence of CVD in these women. Furthermore, high-fructose diets result in elevated plasma concentrations of uric acid via xanthine oxidase (XO) activation, and uric acid elevation is also associated with increased vascular stiffness. However, the mechanisms by which increased xanthine oxidase activity and uric acid contribute to vascular stiffness in obese females remain to be fully uncovered. Accordingly, we examined the impact of XO inhibition on endothelial function and vascular stiffness in female C57BL/6J mice fed a WD or regular chow for 16 wk. WD feeding resulted in increased arterial stiffness, measured by atomic force microscopy in aortic explants (16.19 ± 1.72 vs. 5.21 ± 0.54 kPa, P < 0.05), as well as abnormal aortic endothelium-dependent and -independent vasorelaxation. XO inhibition with allopurinol (widely utilized in the clinical setting) substantially improved vascular relaxation and attenuated stiffness (16.9 ± 0.50 vs. 3.44 ± 0.50 kPa, P < 0.05) while simultaneously lowering serum uric acid levels (0.55 ± 0.98 vs. 0.21 ± 0.04 mg/dL, P < 0.05). In addition, allopurinol improved WD-induced markers of fibrosis and oxidative stress in aortic tissue, as analyzed by immunohistochemistry and transmission electronic microscopy. Collectively, these results demonstrate that XO inhibition protects against WD-induced vascular oxidative stress, fibrosis, impaired vasorelaxation, and aortic stiffness in females. Furthermore, excessive oxidative stress resulting from XO activation appears to play a key role in mediating vascular dysfunction induced by chronic exposure to WD consumption in females.


DNA synthesis and Bcl-2 expression during development of mucous cell metaplasia in airway epithelium of rats exposed to LPS.
Exposure of pulmonary airways to environmental toxins and allergens may cause proliferation of airway epithelial cells and mucous cell metaplasia (MCM); however, it is unclear to what extent proliferating cells differentiate into mucus-storing cells and contribute to MCM. Our previous studies demonstrated that Bcl-2, an inhibitor of apoptosis with cell cycle regulatory functions, is expressed in metaplastic mucous cells. The purpose of the present study was to investigate the number of metaplastic mucous cells that are derived from proliferating epithelial cells and whether Bcl-2 has a role in cell cycle entry in these cells. Rats were intratracheally instilled with 100 microg of LPS from Pseudomonas aeruginosa in 500 microl of saline, and proliferating airway cells were labeled with bromodeoxyuridine (BrdU) by implanting a subcutaneous osmotic pump 24 h before instillation. The volume of stored mucosubstance and the number of mucous cells were increased 10- and 3-fold, respectively, from 24-48 h after instillation. The number of total epithelial cells per millimeter of basal lamina increased, and the number of serous cells per millimeter of basal lamina decreased during this time. Approximately 50% of Alcian blue-periodic acid Schiff-stained mucous cells were labeled with BrdU at 48 h after instillation, suggesting that one-half of the secretory cells were derived from proliferating cells. Furthermore, 50% of the Bcl-2-positive mucous cells were BrdU negative and therefore derived from nonproliferating, preexisting cells. Our findings demonstrate that preexisting and proliferating cells differentiate into mucous cells and compose LPS-induced metaplasia and that Bcl-2 does not have cell cycle regulatory function in these cells.


Fifty years of cancer surgery of the large intestine at Osaka University Hospital.
Surgical procedures were performed in 863 cases of carcinoma of the large intestine in the Second Department of Surgery, Osaka University Hospital, Japan, between 1924 and 1973. There were 262 cases (30.3%) of carcinoma of the colon and 601 cases (69.7%) of carcinoma of the rectum. Sacral resection was the main procedure for rectal carcinoma until 1934. From 1954 through 1962, the abdominoperineal excision became predominant with radical operability 73.3%. Operative mortality declined to 2.3% and the five-year survival rate reached 52.1%. In 1963, sphincter-preserving operations were introduced, after which the radical operability increased to 76.1% and the survival rate to 56.8%. In these years, we selected cases for low anterior resection. Welch's invagination anastomosis and Bacon's pull-through operation according to each indication. For colonic carcinoma, the operative mortality was 2.2%, the five-year survival rate 63.2% and the ten-year survival rate 44.2% in the last period.


[Association of gene polymorphism at cholesterol ester transfer protein locus with obesity and response to dietary intervention in obesity].
To study the association of gene polymorphism at cholesterol ester transfer protein (CETP) locus with obesity and response to dietary intervention in obesity. The PCR-PFLP method was used to detect the polymorphism of CETP gene of 340 adults in Shanghai. The levels of serum lipid profile, including TG, TC, HDL and LDL were analyzed. Obesity was selected to dietary intervention. (1)The genotype frequencies of CETP-TaqIB B1 B1, B1 B2 and B2 B2 were 35.6%, 47.9% and 16.5% respectively, which were in agreement with Hardy-Weinberg equilibrium. There was no significant difference in the distribution of genotypes between the obesity group and control group. The result was same after several influence factors controlled. (2) The levels of HDL were significantly different among genotype groups. Subjects for the B2 B2 genotype had the highest HDL levels. The relationship was steady after adjusting several influence factors. (3)Subjects for the B1 B2 genotype had higher HDL level after intervention, which was significantly different to other genotype groups. After adjusting baseline HDL level and gender, genotype didn't effect the change in HDL. CETP-TaqIB gene polymorphism influenced serum HDL level. But this gene polymorphism at CETP locus wasn't especial in adult obesity. Baseline HDL level influenced the change in HDL response to dietary intervention in three genotype groups.


Sequential caspase-2 and caspase-8 activation upstream of mitochondria during ceramideand etoposide-induced apoptosis.
Recently, caspase-2 was shown to act upstream of mitochondria in stress-induced apoptosis. Activation of caspase-8, a key event in death receptor-mediated apoptosis, also has been demonstrated in death receptor-independent apoptosis. The regulation of these initiator caspases, which trigger the mitochondrial apoptotic pathway, is unclear. Here we report a potential regulatory role of caspase-2 on caspase-8 during ceramide-induced apoptosis. Our results demonstrate the sequential events of initiator caspase-2 and caspase-8 activation, Bid cleavage and translocation, and mitochondrial damage followed by downstream caspase-9 and -3 activation and cell apoptosis after ceramide induction in T cell lines. The expression of truncated Bid (tBid) and the reduction in mitochondrial transmembrane potential were blocked by caspase-2 or caspase-8, but not caspase-3, knockdown using an RNA interference technique. Ceramide-induced caspase-8 activation, mitochondrial damage, and apoptosis were blocked in caspase-2 short interfering RNA-expressing cells. Therefore, caspase-2 acts upstream of caspase-8 during ceramide-induced mitochondrial apoptosis. Similarly, sequential caspase-2 and caspase-8 activation upstream of mitochondria was also observed in etoposide-induced apoptosis. These data suggest sequential initiator caspase-2 and caspase-8 activation in the mitochondrial apoptotic pathway induced by ceramide or etoposide.


Comparison of the effects of inhalational anesthesia with desflurane and total intravenous anesthesia on cardiac biomarkers after aortic valve replacement.
The aim of this study was to compare the effects of using inhalational anesthesia with desflurane with that of a total intravenous (iv) anesthetic technique using midazolam-fentanyl-propofol on the release of cardiac biomarkers after aortic valve replacement (AVR) for aortic stenosis (AS). The specific objectives included (a) determination of the levels of ischemia-modified albumin (IMA) and cardiac troponin I (cTnI) as markers of myocardial injury, (b) effect on mortality, morbidity, duration of mechanical ventilation, length of Intensive Care Unit (ICU) and hospital stay, incidence of arrhythmias, pacing, cardioversion, urine output, and serum creatinine. Methodology and Design: Prospective randomized clinical study. Operation room of a cardiac surgery center of a tertiary teaching hospital. Seventy-six patients in New York Heart Association classification II to III presenting electively for AVR for severe symptomatic AS. Patients included in the study were randomized into two groups and subjected to either a desflurane-fentanyl based technique or total IV anesthesia (TIVA). Blood samples were drawn at preordained intervals to determine the levels of IMA, cTnI, and serum creatinine. The IMA and cTnI levels were not found to be significantly different between both the study groups. Patients in the desflurane group were found to had significantly lower ICU and hospital stays and duration of postoperative mechanical ventilation as compared to those in the TIVA group. There was no difference found in mean heart rate, urine output, serum creatinine, incidence of arrhythmias, need for cardioversion, and 30-day mortality between both groups. The patients in the TIVA group had higher mean arterial pressures on weaning off cardiopulmonary bypass as well as postoperatively in the ICU and recorded lower inotrope usage. The result of our study remains ambiguous regarding the overall protective effect of desflurane in patients undergoing AVR although some benefit in terms of shorter duration of postoperative mechanical ventilation, ICU and hospital stays, as well as cTnI, were seen. However, no difference in overall outcome could be clearly established between patients who received desflurane and those that were managed solely with IV anesthetic technique using propofol.


Effects of bisphenol analogs on thyroid endocrine system and possible interaction with 17β-estradiol using GH3 cells.
This study was conducted using a rat pituitary (GH3) cell line to understand the effects of bisphenol analogs (BPs) on the thyroid endocrine system, in the presence of 17β-estradiol (E2). In the first series of experiments, changes in cell proliferation were examined after exposure to each of ten BPs, in the absence or presence of a median effective concentration (6.4 × 10-10 M) of triiodothyronine (T3). All tested BPs significantly increased cell proliferation, suggesting thyroid hormone (TH) agonistic effects of BPs. BPs did not potentiate the T3-induced cell proliferation at 48 h exposure, while several tested BPs including BPA, BPAF, BPB, BPF, BPS, and BPZ elicited a potentiating effect on the T3-induced cell proliferation at 96 h exposure. These results indicate that TH-antagonistic effects of BPs depend on the tested dose and exposure time. In the second set of experiments, one of the most potent BPs, i.e., BPAF, was selected, and its possible interaction with E2 on the thyroid endocrine system was evaluated. Co-exposure of GH3 cells to 10-12 M E2 showed an additive-like effect. The extent of increase in cell proliferation was more pronounced with a combination of BPAF and E2 than with that of BPA and E2. Significant down-regulation of Trα, Trβ, and Dio2 genes and up-regulation of the Tshβ gene were observed in GH3 cells following co-exposure to BPAF and E2. Our results showed that some BP analogs might influence the thyroid endocrine system, and such perturbation appeared to be enhanced in the presence of E2.


SOCl2-Catalyzed Meyer-Schuster Rearrangement of 3°-Propargylic Alcohols: Synthesis of Densely Arene-Substituted Pyrazolines Bearing Quaternary Centers from α,β-Unsaturated Carbonyl Compounds and Arylhydrazines.
Meyer-Schuster rearrangement of 3°-propargyl alcohol to the corresponding α,β-unsaturated carbonyl compounds under SOCl2 catalysis has been reported. Terminal and internal propargyl alcohols efficiently participated in the reaction. Furthermore, we have demonstrated the synthetic utility of conjugated carbonyl compounds to access densely arene-substituted pyrazolines bearing quaternary centers by reacting with arylhydrazine hydrochloride. Isotopic labeling studies were carried out to gain insights into the reaction mechanism.


Owl monkeys (Aotus nigriceps and A. infulatus) follow routes instead of food-related cues during foraging in captivity.
Foraging at night imposes different challenges from those faced during daylight, including the reliability of sensory cues. Owl monkeys (Aotus spp.) are ideal models among anthropoids to study the information used during foraging at low light levels because they are unique by having a nocturnal lifestyle. Six Aotus nigriceps and four A. infulatus individuals distributed into five enclosures were studied for testing their ability to rely on olfactory, visual, auditory, or spatial and quantitative information for locating food rewards and for evaluating the use of routes to navigate among five visually similar artificial feeding boxes mounted in each enclosure. During most experiments only a single box was baited with a food reward in each session. The baited box changed randomly throughout the experiment. In the spatial and quantitative information experiment there were two baited boxes varying in the amount of food provided. These baited boxes remained the same throughout the experiment. A total of 45 sessions (three sessions per night during 15 consecutive nights) per enclosure was conducted in each experiment. Only one female showed a performance suggestive of learning of the usefulness of sight to locate the food reward in the visual information experiment. Subjects showed a chance performance in the remaining experiments. All owl monkeys showed a preference for one box or a subset of boxes to inspect upon the beginning of each experimental session and consistently followed individual routes among feeding boxes.


Effectiveness of a stress management program in reducing anxiety and depression in nursing students.
This study sought to develop a stress management program based on the arousal-attribution stress model and to evaluate the effectiveness of the program in reducing anxiety and depression experienced by nursing students. Forty-two sophomore and 34 senior nursing students in a private, sectarian, liberal arts college were randomly assigned to experimental and control groups. All subjects were given pre- and posttests consisting of the State form of the State-Trait Anxiety Inventory and the Institute for Personality and Ability Testing Depression Scale. Posttest analysis indicated that the experimental group had significantly lower anxiety and depression than the control group (p less than .05). These results support the use of the arousal-attribution stress model as a theoretical framework for stress management training.


Socioeconomic position and low birth weight among mothers exposed to traffic-related air pollution.
Atmospheric pollution is a major public health concern. It can affect placental function and restricts fetal growth. However, scientific knowledge remains too limited to make inferences regarding causal associations between maternal exposure to air pollution and adverse effects on pregnancy. This study evaluated the association between low birth weight (LBW) and maternal exposure during pregnancy to traffic related air pollutants (TRAP) in São Paulo, Brazil. Analysis included 5,772 cases of term-LBW (<2,500 g) and 5,814 controls matched by sex and month of birth selected from the birth registration system. Mothers' addresses were geocoded to estimate exposure according to 3 indicators: distance from home to heavy traffic roads, distance-weighted traffic density (DWTD) and levels of particulate matter ≤10 µg/m3 estimated through land use regression (LUR-PM10). Final models were evaluated using multiple logistic regression adjusting for birth, maternal and pregnancy characteristics. We found decreased odds in the risk of LBW associated with DWTD and LUR-PM10 in the highest quartiles of exposure with a significant linear trend of decrease in risk. The analysis with distance from heavy traffic roads was less consistent. It was also observed that mothers with higher education and neighborhood-level income were potentially more exposed to TRAP. This study found an unexpected decreased risk of LBW associated with traffic related air pollution. Mothers with advantaged socioeconomic position (SEP) although residing in areas of higher vehicular traffic might not in fact be more expose to air pollution. It can also be that the protection against LBW arising from a better SEP is stronger than the effect of exposure to air pollution, and this exposure may not be sufficient to increase the risk of LBW for these mothers.


Inborn errors of metabolism associated with 3-methylglutaconic aciduria.
A growing number of inborn errors of metabolism (IEM) associated with compromised mitochondrial energy metabolism manifest an unusual phenotypic feature: 3-methylglutaconic (3MGC) aciduria. Two major categories of 3MGC aciduria, primary and secondary, have been described. In primary 3MGC aciduria, IEMs in 3MGC CoA hydratase (AUH) or HMG CoA lyase block leucine catabolism, resulting in a buildup of pathway intermediates, including 3MGC CoA. Subsequent thioester hydrolysis yields 3MGC acid, which is excreted in urine. In secondary 3MGC aciduria, no deficiencies in leucine catabolism enzymes exist and 3MGC CoA is formed de novo from acetyl CoA. In the "acetyl CoA diversion pathway", when IEMs directly, or indirectly, interfere with TCA cycle activity, acetyl CoA accumulates in the matrix space. This leads to condensation of two acetyl CoA to form acetoacetyl CoA, followed by another condensation between acetyl CoA and acetoacetyl CoA to form 3-hydroxy, 3-methylglutaryl (HMG) CoA. Once formed, HMG CoA serves as a substrate for AUH, producing trans-3MGC CoA. Non enzymatic isomerization of trans-3MGC CoA to cis-3MGC CoA precedes intramolecular cyclization to cis-3MGC anhydride plus CoA. Subsequent hydrolysis of cis-3MGC anhydride gives rise to cis-3MGC acid, which is excreted in urine. In reviewing 20 discrete IEMs that manifest secondary 3MGC aciduria, evidence supporting the acetyl CoA diversion pathway was obtained. This biochemical pathway serves as an "overflow valve" in muscle / brain tissue to redirect acetyl CoA to 3MGC CoA when entry to the TCA cycle is impeded.