In Vitro Evaluation of an Immediate Response Starling-Like Controller for Dual Rotary Blood Pumps.
Rotary ventricular assist devices (VADs) are used to provide mechanical circulatory support. However, their lack of preload sensitivity in constant speed control mode (CSC) may result in ventricular suction or venous congestion. This is particularly true of biventricular support, where the native flow-balancing Starling response of both ventricles is diminished. It is possible to model the Starling response of the ventricles using cardiac output and venous return curves. With this model, we can create a Starling-like physiological controller (SLC) for VADs which can automatically balance cardiac output in the presence of perturbations to the circulation. The comparison between CSC and SLC of dual HeartWare HVADs using a mock circulation loop to simulate biventricular heart failure has been reported. Four changes in cardiovascular state were simulated to test the controller, including a 700 mL reduction in circulating fluid volume, a total loss of left and right ventricular contractility, reduction in systemic vascular resistance ( SVR) from 1300 to 600 dyne s/cm5, and an elevation in pulmonary vascular resistance ( PVR) from 100 to 300 dyne s/cm5. SLC maintained the left and right ventricular volumes between 69-214 mL and 29-182 mL, respectively, for all tests, preventing ventricular suction (ventricular volume = 0 mL) and venous congestion (atrial pressures > 20 mm Hg). Cardiac output was maintained at sufficient levels by the SLC, with systemic and pulmonary flow rates maintained above 3.14 L/min for all tests. With the CSC, left ventricular suction occurred during reductions in SVR, elevations in PVR, and reduction in circulating fluid simulations. These results demonstrate a need for a physiological control system and provide adequate in vitro validation of the immediate response of a SLC for biventricular support.


Two-dimensional hydrogen-bond network in bis[(ferrocenylmethyl)dimethylammonium] sulfate pentahydrate.
In the title compound, [Fe(C5H5)(C8H13N)]2(SO4).5H2O, the Fe-C bond lengths lie in the range 2.021 (3)-2.047 (2) A. Intermolecular N-H...O and O-H...O hydrogen bonds link the cations, sulfate anions and water molecules into a two-dimensional hydrogen-bonded network, which stabilizes the crystal packing.


Lymphocyte populations during tuberculosis infection: V beta repertoires.
The immune response to Mycobacterium tuberculosis is mediated by T lymphocytes. We studied the changes in lymphocyte populations occurring in peripheral blood, pleural fluid, and ascites during tuberculosis infection. For this purpose, we compared recent-onset patients (newly converted to positive Mantoux reactions) with previously diagnosed patients (individuals with organic lesions). Recent infection was associated with peripheral blood lymphocytosis involving T lymphocytes expressing either T-cell receptor alpha/beta or gamma/delta. Lymphocytosis involved both CD4 and CD8 cells. On the other hand, we detected no changes in the distribution of peripheral blood lymphocyte populations in previously diagnosed patients. No changes were found in the numbers of B lymphocytes or natural killer cells in either recently infected or previously diagnosed patients. The pleural effusion and ascitic fluid samples contained T lymphocytes expressing T-cell receptor alpha/beta, the majority of which were CD4+. These lymphocytes showed an inverted CD45RA-to-CD45RO ratio, and we found high-level expression of the interleukin-2 receptor (CD25) in some patients. The results are compatible with the existence of periods of cell activation in the pleural fluid (which are disclosed by the appearance of the CD25 antigen and the transition of CD45RA expression to CD45RO) together with nonactivation periods (loss of CD25 and persistence of CD45RO expression). We studied a fraction of the V beta repertoire in peripheral blood in both groups and the same fraction of the V beta repertoire in pleural fluid from patients with tuberculous pleuritis, demonstrating that, in recently infected subjects, lymphocytosis was produced by the increase in lymphocytes which expressed some specific V beta subfamilies that differed from one individual to another. In two of five patients studied, we found significant changes in the V beta repertoire between lymphocytes from peripheral blood and the pleural fluid samples.


Cognitive task load in a naval ship control centre: from identification to prediction.
Deployment of information and communication technology will lead to further automation of control centre tasks and an increasing amount of information to be processed. A method for establishing adequate levels of cognitive task load for the operators in such complex environments has been developed. It is based on a model distinguishing three load factors: time occupied, task-set switching, and level of information processing. Application of the method resulted in eight scenarios for eight extremes of task load (i.e. low and high values for each load factor). These scenarios were performed by 13 teams in a high-fidelity control centre simulator of the Royal Netherlands Navy. The results show that the method provides good prediction of the task load that will actually appear in the simulator. The model allowed identification of under- and overload situations showing negative effects on operator performance corresponding to controlled experiments in a less realistic task environment. Tools proposed to keep the operator at an optimum task load are (adaptive) task allocation and interface support.


Computational study of the competitive binding of valproic acid glucuronide and carbapenem antibiotics to acylpeptide hydrolase.
The efficacy of the antiepileptic drug VPA is decreased by co-administered carbapenems (CBPMs). The mechanism of CBPM selective inhibition of acylpeptide hydrolase (APEH) hydrolysis of VPA-glucuronide (VPA-G) to VPA is unclear due to the lack of APEH structural information. Here we performed homology modeling of the three-dimensional structure of APEH and subsequent docking simulations with a modeled structure to understand this mechanism. Docking simulations indicated that four groups of binding structures were involved in the binding of VPA-G, panipenem, and meropenem to APEH, but only one or two binding structures were involved in the binding of meropenem with an open β-lactam ring structure and other antibiotics involving ampicillin. One of the four VPA-G binding structures was close enough to the APEH catalytic triad to facilitate VPA-G hydrolysis. This binding structure was also the most stable binding structure for panipenem, suggesting potential inhibition of VPA-G hydrolysis by panipenem. Fragment molecular orbital calculations of interaction energies of amino acid residues of APEH with VPA-G, panipenem, and meropenem indicated that the binding structure for panipenem closest to the catalytic triad is stabilized upon APEH interaction. These data suggest that APEH binding characteristics with CBPMs may help explain the selective inhibition of APEH by CBPMs.


Recognition of Client Proteins by the Proteasome.
The ubiquitin proteasome system controls the concentrations of regulatory proteins and removes damaged and misfolded proteins from cells. Proteins are targeted to the protease at the center of this system, the proteasome, by ubiquitin tags, but ubiquitin is also used as a signal in other cellular processes. Specificity is conferred by the size and structure of the ubiquitin tags, which are recognized by receptors associated with the different cellular processes. However, the ubiquitin code remains ambiguous, and the same ubiquitin tag can target different proteins to different fates. After binding substrate protein at the ubiquitin tag, the proteasome initiates degradation at a disordered region in the substrate. The proteasome has pronounced preferences for the initiation site, and its recognition represents a second component of the degradation signal.


Dose-dependence and reversibility of the hemoconcentrating and hypotensive activities of atrial natriuretic peptide in binephrectomized rats.
In addition to its blood pressure lowering effect, atrial natriuretic peptide (ANP) infusion, increases hematocrit and decreases plasma volume by inducing a transfer of plasma fluid from the vascular to the interstitial compartment. We explored the dose-dependence as well as the reversibility of these actions by measuring changes in mean arterial pressure (MAP), hematocrit and plasma protein concentration (PPC) in anesthetized acutely binephrectomized Sprague-Dawley rats. Infusion of ANP (10, 100 or 1000 ng/kg/min for 45 min) dose-dependently reduced MAP (+2.3 +/- 1.8, -5.8 +/- 2.5 and -8.6 +/- 1.3%) and increased hematocrit (1.7 +/- 0.4, 8.1 +/- 0.4 and 9.0 +/- 0.6%), corresponding to calculated decreases in plasma volume of 3.0 +/- 0.6, 13.1 +/- 0.6 and 14.4 +/- 0.9% respectively. PPC increased significantly less than expected for a plasma volume reduction without proteins extravasation indicating that some loss of plasma proteins occurred in response to ANP. Both the reduction in MAP and plasma volume were reversible within 45 min after discontinuation of ANP infusion. During the recovery period, PPC decreased to values lower than baseline suggesting that the hemodilution was not associated with a detectable return of proteins into the circulation. Thus, in binephrectomized rats, infusion of ANP induced a dose-dependent and reversible reduction in arterial pressure and plasma volume through an extrarenal mechanism. Moreover, ANP dose-dependently increased the vascular permeability to proteins; the escaped proteins remained out of the vascular space for at least the duration of the experiment (ie 45 min post-infusion).


7 alpha-Dehydroxylation of bile acids by resting cells of a Eubacterium lentum-like intestinal anaerobe, strain c-25.
7 alpha-Dehydroxylation of cholic acid and chenodeoxycholic acid by whole cells of strain c-25, a Eubacterium lentum-like intestinal anaerobe, was studied. 7 alpha-Dehydroxylase activity was observed only in whole cells grown in the presence of the primary bile acid (cholic acid or chenodeoxycholic acid). Chenodeoxycholic acid was twice as effective as cholic acid as an inducer. Although cells grown in the presence of chenodeoxycholic acid had no significant substrate specificity for the two primary bile acids, cells grown in the presence of cholic acid showed two times greater activity against cholic acid than chenodeoxycholic acid. Exposure of cell suspensions to atmospheric oxygen resulted in little loss of the 7 alpha-dehydroxylase activity. The induced enzyme had an optimal pH range of 7.3 to 7.7. Although adding flavin mononucleotide to the growth medium significantly increased the 7 alpha-dehydroxylation of bile acids without an increase in cell growth, inhibition of the enzyme activity was observed in the resting cell system when flavin mononucleotide was included in the reaction mixture.


[Bilateral papillary cystadenoma of the epididymis].
One case of bilateral papillary cystadenoma of the epididymis without the development of Hippel--Lindau disease is reported. This rare, benign tumour should be considered in the differential diagnostics of the enlargment of the epidimdyis in young and middle aged males. Histological picture of the tumour described seems to evidence, that it originates from the ductuli efferentes.


THE FINE STRUCTURE AND MODE OF ATTACHMENT OF THE SHEATHED FLAGELLUM OF VIBRIO METCHNIKOVII.
The sheathed flagellum of Vibrio metchnikovii was chosen for a study of the attachment of the flagellum to the bacterial cell. Normal and autolysed organisms and isolated flagella were studied by electron microscopy using the techniques of thin sectioning and negative staining. The sheath of the flagellum has the same layered structure as the cell wall of the bacterium, and in favourable thin sections it appears that the sheath is a continuation of the cell wall. After autolysis the sheath is usually absent and the core of the flagellum has a diameter of 120 A. Electron micrographs of autolysed bacteria negatively stained with potassium phosphotungstate show that the core ends in a basal disc just inside the plasma membrane. The basal disc is about 350 A in diameter and is thus considerably smaller than the "basal granules" described previously by other workers.


Cell and Protein Fouling Properties of Polymeric Mixtures Containing Supramolecular Poly(ethylene glycol) Additives.
Fouling properties of new biomaterials are important for the performance of a material in a biological environment. Here, a set of three supramolecular polymeric additives consisting of ureidopyrimidinone (UPy)-functionalized poly(ethylene glycol) (UPyPEG) were formulated with UPy-modified polycaprolactone into thin supramolecular material films. The antifouling properties of these material films were determined by investigation of the relation of cell adhesion and protein adsorption on these materials films. The presence of the UPyPEG additives at the surface of the films was evident by an increased hydrophilicity. Adhesion of human epithelial and endothelial cells was strongly reduced for two of the UPyPEG-containing films. Analysis of adsorption of the first three proteins from the Vroman series, albumin, γ-globulin, and fibrinogen, using quartz crystal microbalance with dissipation in combination with viscoelastic modeling, revealed that the surfaces containing the UPyPEG additives had a limited effect on adsorption of these proteins. Despite a limited reduction of protein adsorption, UPyPEG-containing mixtures were non-cell-adhesive, which shows that non-cell-adhesive properties of supramolecular polymer surfaces are not always directly correlated to protein adsorption.


Current status of haploidentical stem cell transplantation.
Haploidentical stem cell transplantation is an alternative transplant strategy for patients without an human leucocyte antigen-matched donor. The historical experience with haploidentical stem cell transplantation has been characterised by the immunological consequences of crossing a major histocompatibility barrier, namely graft-versus-host disease (GVHD), graft rejection and impaired immune reconstitution. Ex vivo T-cell depletion of the graft may reduce the risk of GVHD, but at the expense of a higher risk of engraftment failure and relapse of the underlying malignancy. Myeloablative transplant strategies using vigorously T-cell-depleted 'megadose' stem cells appear to have improved the outcomes of selected patients with acute leukaemia. Non-myeloablative stem cell transplantation strategies, in which mixed chimaerism as a platform for adoptive cellular immunotherapy is intentionally induced, show promise for limiting GVHD and lessening transplant-related mortality. Future approaches, based on promising preclinical and early clinical observations, may include selective allodepletion of the graft, and manipulation of the cellular environment post-transplant using selected cellular populations or immunomodulatory soluble factors.


Bioaccumulation and biomagnification of perfluoroalkyl acids and precursors in East Greenland polar bears and their ringed seal prey.
The bioaccumulation and biomagnification of 22 major perfluoroalkyl substances (PFAS) were investigated in tissues of polar bears (Ursus maritimus) and their major prey species, the ringed seal (Pusa hispida), from the Scoresby Sound region of East Greenland. In polar bear liver the mean Σ4PFSA (perfluoroalkyl sulfonic acid) concentration (C4, C6, C8 and C10) was 2611 ± 202 ng/g wet weight (ww; 99% perfluorooctane sulfonate (PFOS)) and two orders of magnitude higher than the 20 ± 3 ng/g ww (89% PFOS) concentration in fat. The mean Σ4PFSAs in seal liver was 111 ± 5 ng/g ww (98% PFOS) and three orders of magnitude higher relative to the 0.05 ± 0.01 ng/g ww concentration in blubber (100% perfluorohexane sulfonate). Perfluoro-1-octane sulfonamide (FOSA) was quantifiable in bear (mean 10 ± 1.4 ng/g ww) and seal (mean 0.6 ± 0.1 ng/g ww) liver but not in fat or blubber. The mean Σ13PFCAs (C4-C18; perfluoroalkyl carboxylic acids) in bear liver (924 ± 71 ng/g ww) was much greater than in seal liver (74 ± 6 ng/g ww). In bear fat and seal blubber, the mean Σ13PFCAs were 15 ± 1.9 and 0.9 ± 0.1 ng/g ww, respectively. Longer chain C11 to C14 PFCAs dominated in bear fat and seal blubber (60-80% of Σ13PFCA), whereas shorter-chain C9 to C11 PFCAs dominated in the liver (85-90% of Σ13PFCA). Biomagnification factors (BMFs) were orders of magnitude greater for PFHxS and C9 to C13 PFCAs when based on bear liver to seal blubber rather than bear liver to seal liver, and PFCA (C9 to C13) BMFs decreased with increasing chain length. Seal blubber to bear liver BMFs better reflects the dietary exposure relationship of PFAS between bears and seals.


[Relation of fingernail mineral concentrations to bone mineral density in elderly Japanese women].
Metacarpal bone mineral density, and concentrations of calcium (Ca), iron (Fe), magnesium (Mg), zinc (Zn) and phosphorus (P) in fingernails were measured in 30 elderly women. Significant correlation between bone mineral density and body weight was seen, and higher values of bone mineral density were observed in those subjects walking daily without the aid of a cane or assistance. Among the 5 minerals in fingernails, a high positive correlation was found between Ca and P concentrations. Concentration of Zn in fingernails was significantly but negatively correlated with bone mineral density (r = -0.399), and a significant positive correlation of Ca/Zn ratio of fingernails was observed with bone mineral density (r = 0.421). The content of Zn in nails may be affected by alterations in bone Zn status and a potential application of nail Zn level or Ca/Zn ratio as an indicator of senile osteoporosis is suggested.


Assessing Community Health Information Systems: Evidence from Child Health Records in Food Insecure Areas of the Ethiopian Highlands.
This study assessed the completeness of child health records maintained and collected within community health information system in Ethiopia. A household listing was carried out in 221 enumeration areas in food insecure areas of Ethiopia to determine the presence of a child less than 24-months. This list of children was then compared against the information stored at the local health posts. A household survey was administered to a sample of 2155 households that had a child less than 24-months of age to assess determinants and consequences of exclusion from the health post registers. Out of the 10,318 children identified during the listing, 36% were found from the health post records. Further analysis based on the household survey data indicated that health posts that had adopted nationally recommended recordkeeping practices had more complete records (p < 0.01) and that children residing farther from health posts were less likely to be found from the registers (p < 0.05). Mothers whose child was found from the registers were more likely to know a health extension worker (p < 0.01), had a contact with one (p < 0.01), and their child was more likely to have received growth monitoring (p < 0.05). The incompleteness of the data collected at the health posts poses a challenge for effective implementation of the national health extension program and various complementary programs in Ethiopia.


Development of a mariner-based transposon for use in Sorangium cellulosum.
In order to generate marked insertions in the myxobacterium Sorangium cellulosum, a transposon based on the eukaryotic mariner transposon was developed. The transposition frequency was increased with the use of a mutated tnp gene. The transposon randomly inserts into the chromosome, as demonstrated by targeted mutagenesis of the epoK gene.


Value of symptoms and additional diagnostic tests for colorectal cancer in primary care: systematic review and meta-analysis.
To summarise available evidence on diagnostic tests that might help primary care physicians to identify patients with an increased risk for colorectal cancer among those consulting for non-acute lower abdominal symptoms. PubMed, Embase, and reference screening. Study eligibility criteria Studies were selected if the design was a diagnostic study; the patients were adults consulting because of non-acute lower abdominal symptoms; tests included signs, symptoms, blood tests, or faecal tests. Study appraisal and synthesis methods Two reviewers independently assessed quality with a modified version of the QUADAS tool and extracted data. We present diagnostic two by two tables and pooled estimates of sensitivity and specificity. We refrained from pooling when there was considerable clinical or statistical heterogeneity. 47 primary diagnostic studies were included. Sensitivity was consistently high for age >or=50 (range 0.81-0.96, median 0.91), a referral guideline (0.80-0.94, 0.92), and immunochemical faeces tests (0.70-1.00, 0.95). Of these, only specificity of the faeces tests was good. Specificity was consistently high for family history (0.75-0.98, 0.91), weight loss (0.72-0.96, 0.89), and iron deficiency anaemia (0.83-0.95, 0.92), but all tests lacked sensitivity. None of these six tests was (sufficiently) studied in primary care. Although combinations of symptom and results of immunochemical faeces tests showed good diagnostic performance for colorectal cancer, evidence from primary care is lacking. High quality studies on their role in the diagnostic investigation of colorectal cancer in primary care are urgently needed.


Sleep-disordered breathing in hypertensive disorders of pregnancy: a BMI-matched study.
Sleep-disordered breathing is more common in hypertensive disorders during pregnancy; however, most studies have not adequately accounted for the potential confounding impact of obesity. This study evaluated the frequency of sleep-disordered breathing in women with gestational hypertension and pre-eclampsia compared with body mass index- and gestation-matched normotensive pregnant women. Women diagnosed with gestational hypertension or pre-eclampsia underwent polysomnography shortly after diagnosis. Normotensive controls body mass index-matched within ±4 kg m-2 underwent polysomnography within ±4 weeks of gestational age of their matched case. The mean body mass index and gestational age at polysomnography were successfully matched for 40 women with gestational hypertension/pre-eclampsia and 40 controls. The frequency of sleep-disordered breathing in the cases was 52.5% compared with 37.5% in the control group (P = 0.18), and the respiratory disturbance index overall did not differ (P = 0.20). However, more severe sleep-disordered breathing was more than twice as common in women with gestational hypertension or pre-eclampsia (35% versus 15%, P = 0.039). While more than half of women with a hypertensive disorder of pregnancy meet the clinical criteria for sleep-disordered breathing, it is also very common in normotensive women of similar body mass index. This underscores the importance of adjusting for obesity when exploring the relationship between sleep-disordered breathing and hypertension in pregnancy. More severe degrees of sleep-disordered breathing are significantly associated with gestational hypertension and pre-eclampsia, and sleep-disordered breathing may plausibly play a role in the pathophysiology of pregnancy hypertension in these women. This suggests that more severe sleep-disordered breathing is a potential therapeutic target for reducing the prevalence or severity of hypertensive disorders in pregnancy.


[Medication of the month. Duloxetine (Cymbalta)].
Duloxetine (Cymbalta is an antidepressant of the class of serotonin noradrenaline reuptake inhibitors. The efficacy of duloxetine 60 mg/day has been well demonstrated in the acute and long term treatment of major depression. The level of effectiveness of duloxetine is particularly high and associated with a shorter latency of action. Duloxetine also exhibits antinociceptive properties independently of the antidepressant effect. The side-effect profile of duloxetine is particularly good and similar to selective serotonin reuptake inhibitors with mainly nausea. In total, duloxetine represents a real progress in the pharmacological treatment of major depression.


UREMP, RO-REMP, and OO-REMP: Hybrid perturbation theories for open-shell electronic structure calculations.
An accurate description of the electron correlation energy in closed- and open-shell molecules is shown to be obtained by a second-order perturbation theory (PT) termed REMP. REMP is a hybrid of the Retaining the Excitation degree (RE) and the Møller-Plesset (MP) PTs. It performs particularly encouragingly in an orbital-optimized variant (OO-REMP) where the reference wavefunction is given by an unrestricted Slater determinant whose spin orbitals are varied such that the total energy becomes a minimum. While the approach generally behaves less satisfactorily with unrestricted Hartree-Fock references, reasonable performance is observed for restricted Hartree-Fock and restricted open-shell Hartree-Fock references. Inclusion of single excitations to OO-REMP is investigated and found-as in similar investigations-to be dissatisfying as it deteriorates performance. For the non-multireference subset of the accurate W4-11 benchmark set of Karton et al. [Chem. Phys. Lett. 510, 165-178 (2011)], OO-REMP predicts most atomization and reaction energies with chemical accuracy (1 kcal mol-1) if complete-basis-set extrapolation with augmented and core-polarized basis sets is used. For the W4-11 related test-sets, the error estimates obtained with the OO-REMP method approach those of coupled-cluster with singles, doubles and perturbative triples [CCSD(T)] within 20%-35%. The best performance of OO-REMP is found for a mixing ratio of 20%:80% MP:RE, which is essentially independent of whether radical stabilization energies, barrier heights, or reaction energies are investigated. Orbital optimization is shown to improve the REMP approach for both closed and open shell cases and outperforms coupled-cluster theory with singles and doubles (CCSD), spin-component scaled Møller-Plesset theory at second order (SCS-MP2), and density functionals, including double hybrids in all the cases considered.


The role of parent and child self-regulation in children's glycemic control.
Type 1 diabetes mellitus (T1DM) is a lifelong, metabolic disorder, typically arising in childhood and adolescence. Despite recent advances in diabetes management techniques, glycemic control remains substandard for many individuals This study examined the role of parental and child self-regulation in predicting effective glycemic control in children and adolescents with Type 1 diabetes mellitus (T1DM). Sixty-three families (with children aged 3-18 years) with T1DM participated. Child, maternal, and paternal measures of temperament, including surgency (behavioral self-regulation), negative affect (emotional selfregulation), and effortful control (cognitive self-regulation) were collected, along with demographic information and haemoglobin A1c (glycemic control). Higher parental and child effortful control was associated with better glycemic control. Higher child negative emotionality was associated with poorer glycemic control. No significant interactions between child and parent measures were identified. Both parental and child self-regulation play an independent role in glycemic control, and serve as targets for intervention in improving diabetes management in children and adolescents. (PsycINFO Database Record


A histologic study of the auto-allergic testis lesion in the guinea pig.
The auto-allergic lesion in guinea pigs inoculated with homologous testis plus the Freund adjuvant was investigated histologically. The lesion was found to consist of disseminated foci of perivenous inflammation, lymphocytes and histiocytes predominating in the cellular infiltrate, with invasion of epididymal, rete, and seminiferous tubules and destruction of tubular contents. Guinea pigs up to 800 gm. showed a rapidly progressing diffuse hypo- or aspermatogenesis, which appeared to be secondary to the inflammatory disease. In these animals, the process resolved leaving an atrophic testis with few or no indications of the preceding inflammation and fibrotic scarring only in the rare instances in which actual necrosis of connective tissue elements had occurred. In 1200 gm. animals there was no general hypospermatogenesis and the late findings were limited to foci of aspermatogenesis. This disease then is an experimental auto-allergic orchitis followed by testicular atrophy without scarring. Its morphologic similarity to mumps orchitis and to sterility with "germinal cell aplasia" in man is commented on.


Cognitive, psychiatric and motor response to galantamine in Parkinson's disease with dementia.
Cholinesterase inhibitors with additional nicotinic activity, such as galantamine, may be useful in PD patients with dementia (PDD) since stimulation of nicotinic receptors may prevent the down-regulation that is likely to accompany cholinesterase inhibition and facilitate dopamine release in the striatum. Sixteen PDD patients (six female) with onset of cognitive impairment after at least one year with parkinsonism participated in this open-label trial of galantamine. Cognitive, psychiatric, and motor symptoms were assessed before and after 8 weeks of treatment with galantamine using unstructured clinical assessment as well as rating scales including the Mini-Mental State Examination (MMSE), clock drawing test, verbal fluency and selected items from the Neuropsychiatric Inventory (NPI). Age (mean, SD) was 75.6 (5.2) years, duration of PD 13.4 (5.9), duration of dementia 2.1 (1.7) years, Hoehn and Yahr score was 3.8 (0.8) and baseline MMSE score was 17.7 (6.7). Side-effects caused discontinuation in three patients, but were rare and mild in the remaining 13. Improvement of global mental symptoms was noted in eight patients, whereas worsening was reported in four. Hallucinations improved in seven of the nine patients with hallucinations before treatment. Parkinsonism improved in six patients, but a mild worsening of tremor was noted in three. Clock-drawing improved (p=0.016), and trends towards improvement on MMSE (p=0.09) and verbal fluency (p=0.16) were found. Although controlled trials are needed, the findings suggest that galantamine is useful in patients with PDD.


Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis.
Disease progression in response to infection can be strongly influenced by both pathogen burden and infection-induced immunopathology. While current therapeutics focus on augmenting protective immune responses, identifying therapeutics that reduce infection-induced immunopathology are clearly warranted. Despite the apparent protective role for murine CD8⁺ T cells following infection with the intracellular parasite Leishmania, CD8⁺ T cells have been paradoxically linked to immunopathological responses in human cutaneous leishmaniasis. Transcriptome analysis of lesions from Leishmania braziliensis patients revealed that genes associated with the cytolytic pathway are highly expressed and CD8⁺ T cells from lesions exhibited a cytolytic phenotype. To determine if CD8⁺ T cells play a causal role in disease, we turned to a murine model. These studies revealed that disease progression and metastasis in L. braziliensis infected mice was independent of parasite burden and was instead directly associated with the presence of CD8⁺ T cells. In mice with severe pathology, we visualized CD8⁺ T cell degranulation and lysis of L. braziliensis infected cells. Finally, in contrast to wild-type CD8⁺ T cells, perforin-deficient cells failed to induce disease. Thus, we show for the first time that cytolytic CD8⁺ T cells mediate immunopathology and drive the development of metastatic lesions in cutaneous leishmaniasis.


Quality and reporting of trial design in scientific papers in Anaesthesia over 25 years.
We determined how the quality of trial design and its reporting in scientific papers published in Anaesthesia has changed in the last 25 years. All articles between the years 1983-87 and 2003-07 were reviewed and classified according to methodology. Reporting and trial design of all prospective, comparative clinical interventional trials were compared between the two time periods using 12 criteria. Fewer articles now originate from the United Kingdom and Ireland than 25 years ago. Although fewer human interventional trials are now published in Anaesthesia, the quality of these trials has improved in terms of study design, bias control and proper disclosure. Significant improvements were observed in all criteria of trial design except for the declaration of non-primary adverse outcomes and the minimisation of the risk of type I errors. Further improvements could still be made with respect to sample size calculation, description of the method of randomisation, and blinding.


Immunogenicity and tolerogenicity of self-major histocompatibility complex peptides.
Mechanisms involved in self-antigen processing and presentation are crucial in understanding the induction of self-tolerance in the thymus. We examined the immunogenicity of determinants from major histocompatibility complex (MHC) molecules that are expressed in the thymus and have tested peptides derived from the polymorphic regions of class I and class II molecules. We found that two peptides corresponding to NH2 termini of the class II alpha and beta chains (Ak alpha 1-18 and Ak beta 1-16) could bind to self-Ak molecules with high affinity and, surprisingly, were immunogenic in that they could elicit strong proliferative T cell responses in B10.A mice (Ak, Ek). Neonatal injection of peptide Ak beta 1-16 resulted in complete unresponsiveness to this peptide at 8 wk of age showing that these T cells were susceptible to tolerance induction. We have also tested certain class I MHC peptides and showed that some can interact efficiently with class II MHC peptides to induce an autoreactive T cell proliferative response. Among these class I peptides is one (Dd 61-85) that has the capacity to bind to self-Ia without being immunogenic, and therefore represents an MHC determinant that had induced thymic self-tolerance. We conclude that some self-MHC molecules can be processed into peptides that can be presented in the context of intact class II molecules at the surface of antigen-presenting cells. Autoreactive T cells recognizing optimally processed self-peptide/MHC complexes are eliminated during development, whereas other potentially autoreactive T cells escape clonal inactivation or deletion. Incomplete tolerance to self-antigens enriches the T cell repertoire despite the fact that such T cells may eventually become involved in autoimmune disease.


Interferon-induced pulmonary sarcoidosis.
A further new case of sarcoidosis associated with the use of interferon (IFN) in the classical treatment of chronic hepatitis C (CHC) is reported. During the last two years, more than 20 cases of interferon-induced sarcoidosis have been described in the literature and about half of these cases have involved CHC. Therefore this disorder appears more common than originally thought two years ago, possibly due to the more frequent use of interferon therapy and an improvement in the methods of diagnosis.


Key considerations for successful implementation of maternal immunization programs in low and middle income countries.
The Maternal Neonatal Tetanus Elimination program is proof of concept for the feasibility and potential for maternal immunization to reduce neonatal mortality particularly in low and middle-income countries. Introduction of any additional vaccine into the antenatal space, such as Influenza and Pertussis, and potentially Respiratory Syncytial Virus and Group B Streptococcus vaccines in the future, requires strengthening of antenatal care and immunization services. Successful implementation also requires robust disease surveillance in pregnant women and neonates and active surveillance for adverse events following immunization to monitor the impact and ensure the safe use of the vaccine. This review outlines five key elements essential for successful implementation of a maternal immunization program focusing particularly on low and middle-income countries. These include; relevant considerations in supporting a decision to undertake a maternal immunization program including knowledge of local disease epidemiology, involvement of the consumer, healthcare provider recommendation, equitable access to maternal vaccination, and systems for disease surveillance, program evaluation and safety monitoring.


A-scan ultrasonography in the diagnosis of orbital dermoid cysts.
Eleven patients with anterior and deep orbital masses had A-scan ultrasonography. The ultrasonograms were all similar and demonstrated a dermoid-like pattern of low internal reflectivity and a high-rising, double-peaked posterior surface spike. Although the postoperative pathologic findings in seven cases confirmed the clinical diagnosis of dermoid cyst, other lesions, such as epidermoid cyst, sebaceous cyst, Graves's myopathy, and Ewing's sarcoma were found to show a similar ultrasonographic pattern. This stresses the importance of computed tomography in the diagnosis of orbital tumors.


The accuracy of antenatal ultrasound screening in Malta: a population-based study
To analyse the accuracy of antenatal ultrasound screening in Malta, comparing detection rates within the private and public sectors, and with the rest of Europe. To assess local trends in accuracy for each organ system. Ethics approval was obtained to gather routinely collected data from the national congenital anomalies registry between 2016 and 2018. This was analysed to determine local antenatal ultrasound accuracy rates and trends. Electronic medical appointment record data was also used to indirectly determine whether a significant difference existed in the detection of antenatal anomalies in mothers scanned privately and those scanned within the public sector. χ2-for-trend was used to analyse changes in the accuracy rates. European Surveillance of Congenital Anomalies (EUROCAT) data was used to compare scanning accuracy in Malta and other EUROCAT centres. The local rate of undetected congenital anomalies was 62.0% for public scans and 83.9% for private scans. Local trends over the three-year period showed an improvement in accuracy rates in detecting isolated syndromes (p=0.05), anomalies of the renal system (p=0.02) and craniofacial anomalies (p=0.05). Malta's overall performance was similar to other EUROCAT centres. Scans carried out within the public sector are more accurate than private scans, and Malta's overall performance was similar to other EUROCAT centres.


[Fraction of absorbed photosynthetically active radiation over summer maize canopy estimated by hyperspectral remote sensing under different drought conditions.]
Fraction of absorbed photosynthetically active radiation (fAPAR) is one of the important remote sensing model parameters of vegetation productivity. However, the crop canopy fAPAR estimation during growing season under different drought conditions has not been reported yet. In this study, the characteristics of summer maize canopy fAPAR and spectral reflectance during growing season under different drought stresses and the relationships of fAPAR with reflectance, the first derivative spectral reflectance and vegetation indices were examined based on the hyperspectral reflectance and fAPAR data from the summer maize drought manipulation experiment with five irrigation levels in 2015. Under mild water stress and sufficient water supply conditions, fAPAR was higher, with the maximum value of 0.7. Under severe water stress and severe persistent drought, fAPAR was lower, with the minimum value of 0.06. Reflectance of visible and shortwave bands increased and near infrared reflectance decreased with increasing drought. The fAPAR was negatively related with visible bands and shortwave bands, but positively correlated with near infrared. Visible and shortwave band reflectance had significant correlation with fAPAR, especially at 383, 680 and 1980 nm, with all the correlation coefficients being more than -0.87. The strong and stable relationship between the first derivative spectral reflectance and fAPAR appeared at 580, 720 and 1546 nm, with the correlation coefficients being -0.91, 0.89 and 0.88, respectively. There were linear or logarithm relationships between fAPAR with nine vegetation indices. Among the nine indices, the enhanced vegetation index (EVI), renormalized difference vegetation index (RDVI), soil adjusted vegetation index (SAVI), and modified soil adjusted vegetation index (MSAVI) performed well with the correlation coefficient being higher than 0.88, and the average relative error (RMAE) 16.6%, 16.6%, 16.7% and 16.2%, respectively. Based on the logarithmic relationship between first derivative spectral reflectance and fAPAR, the simulation effect was best at the band of (720±5) nm, with a correlation coefficient of 0.86. The correlation coefficient of the relationship between fAPAR and reflectance was less than 0.81. The results could provide fAPAR simulation for remote sensing model of vegetation productivity and drought warning.


Influence of injected pluripotential (EK) cells on haploid and diploid parthenogenetic development.
A number of pluripotential embryo-derived EK cells were introduced into the blastocoele of haploid and diploid parthenogenetic embryos which were subsequently transferred to suitable recipients. At autopsy on day 10 or 11 of pseudopregnancy 22% of decidua in the diploid series contained somite-stage embryos while an additional 12% contained abnormal egg cylinder-like sacs. In the haploid series, 7% of the decidua contained somite-stage embryos and an additional 5% contained abnormal 'sacs'. In 'injected' diploid and haploid 'controls' in which the zonae were pierced with an empty injection pipette 3% and 0% respectively of decidua in these two series contained somite-stage embryos, while an additional 17% and 3% respectively of decidua in these two series contained abnormal sacs. GPI analysis revealed that the EK cells were incorporated into somite-stage conceptuses in only one third of the diploids and in none of the haploid embryos. Although the presence of EK cells considerably increases the chance of normal embryonic development taking place, a detectable contribution from the EK cells into the resulting somite-stage embryo is apparently not necessary. Possible mechanisms allowing successful early post-implantation development to occur in this study are discussed.


Ossifying fibromyxoid tumor may express CD56 and CD99: a case report.
Ossifying fibromyxoid tumor (OFMT) is an uncommon soft tissue neoplasm characterized by a combination of myxoid and/or fibrous stroma with areas of ossification. Although most authors postulate a neuroectodermal origin for this peculiar tumor, there is no agreement in the literature regarding its histogenesis. In this article, we present the immunohistochemical findings of a case of a 39-year-old white male with an OFMT of the soft tissue in the mandibular region. The tumor was positive to S-100 protein, glial fibrillary acidic protein, CD99, CD56 and negative to smooth muscle actin, cytokeratins AE1/AE3, epithelial membrane antigen, and CD68. To the best of our knowledge, this is the first case reported to be positive to CD56 and CD99. Immunoreactivity to these two antibodies, together with reactivity for S-100 protein and glial fibrillary acidic protein, suggests that OFMT is of a neuroectodermal origin. In our opinion, in the absence of reactivity to at least one neuroectodermal marker one should seriously question a diagnosis of OFMT.


Cross-contamination: Comparison of Nasal and Chronic Leg Ulcer Staphylococcus aureus Strains Isolated from the Same Patient.
The aim of this study was to investigate the occurrence of bacterial cross-contamination between the nasal cavity and leg ulcers. Sixteen patients were included in the study. Staphylococcus aureus was isolated from the leg ulcer of 13 patients and 6 of these patients also harboured S. aureus in the nasal cavity. Klebsiella oxytoca was found in the ulcer and the nasal cavity of one patient. PFGE analysis revealed that patients harbouring S. aureus both in the nasal cavity and the leg ulcer had the same bacterial type at both sites. None of the S. aureus isolates were methicillin resistant.


Generalized predictive equation for hematocrit by biological impedancemetry.
Bioelectrical impedancemetry (BIA) has been used to evaluate hemorheological parameters from whole body measurements. In a previous study, we have determined a set of predictive equations for hematocrit, whole blood viscosity and plasma viscosity in athletes. In another previous study, we also found other predictive equations in sedentary lean and obese subjects. This study aims at developing more generalized BIA-derived predictive equations for hemorheological parameters in both sedentary and trained individuals. 72 subjects, either athletes, sedentary obese or insulin resistant patients (33.57+/-1.60 yr; 80.81+/-2.06 kg; 171.03+/-1.19 cm) were enrolled into the study. Body composition was assessed with a multifrequency bioelectrical impedancemeter (Dietosystem Human IM Scan) using low intensity at the following frequencies: 1, 5, 10, 50 and 100 kHz. Viscometric measurements were done at 1000 s(-1) with a falling ball viscosimeter (MT 90 Medicatest). Hematocrit (Hct) was measured with microcentrifuge. Hematocrit was correlated with impedance (Z) measurements at 50 kHz (r=-0.591, p=0.01). A generalized empirical predictive equation can thus be proposed. These findings further suggest that one can predict hematocrit in the general population with whole body electric properties.


Pharmacotherapy for biochemical recurrences after therapy for localised prostate cancer.
Prostate-specific antigen (PSA) has revolutionised screening for and monitoring of prostate cancer (CaP). Currently, most men failing potentially curative CaP therapies develop biochemical evidence of recurrent disease (defined by detectable PSA levels) long before the onset of clinical symptoms. Androgen deprivation therapy (ADT) remains the gold standard for the treatment of metastatic CaP. Conventional ADT is orchiectomy or luteinising hormone-releasing hormone agonists. ADT is most commonly associated with side effects such as erectile dysfunction, decreased libido, gynecomastia and osteoporosis. Intermittent ADT or oral anti-androgens may limit the side effects associated with ADT while retaining efficacy. Although widely studied, the optimal timing to begin ADT remains an important and unanswered question. Future advances in gene therapy and immunotherapy hold the greatest promise to provide effective treatments against recurrent CaP while minimising morbidity.


Non-endocrine applications of somatostatin and octreotide acetate: facts and flights of fancy.
Somatostatin, originally detected by Krulich and ultimately isolated by Brazeau, was initially described as a growth hormone release-inhibiting factor. Subsequent investigation into the use of native somatostatin and the development of long-acting somatostatin analogues, especially octreotide acetate, have fostered increasing uses of these compounds. Though the clinical and investigational uses of somatostatin and its analogues are varied, one central theme remains constant: the ability of these agents to suppress circulating peptide levels. This article, a review of the current non-endocrine applications of somatostatin and its analogues, covers a wide range of potential applications for somatostatin-like compounds. These include use in cirrhosis and variceal bleeding, peptic ulcer disease, pancreatic fistulas, acute and chronic pancreatitis, dumping syndrome, cancer therapy, small bowel fistulas, psoriasis, pain control, and autonomic hypotension. Somatostatin may also play a role in the development and potential treatment of neurologic disease and may have profound found influence on behavior.


T cell receptor excision circle levels in CD94-expressing CD8 T Cells during graft-versus-host disease.
T cell receptor excision circles (TRECs) have been suggested to be useful markers of recent thymic output and graft-versus-host disease (GVHD) was thought to have an adverse effect on thymic output. On the other hand, TREC concentrations are diluted with T cell expansion. The C-type lectin superfamily inhibitory receptor CD94 expression on T cells might be a consequence of CD8 T cell expansion. Therefore, this study was designed to analyse TREC DNA level in CD4 and CD8 T cell subset expressing CD94 during GVHD. We investigated TREC DNA copy numbers (TREC levels) of CD4+, CD94+/CD8+ and CD94-/CD8+ T cells in 24 patients who had undergone allogeneic stem cell transplantation and also of in vitro activated and expanded CD94-expressing cells by immobilised anti-CD3 mAb and IL-15. TREC level of CD94+/CD8+ T cells in patients with chronic GVHD was lower than that in patients with no GVHD and with remission status of GVHD. In vitro activated and expanded CD94-expressing cells had a significantly lower TREC level than that in untreated CD8 cells. Therefore, the low TREC level of CD94+/CD8+ T cells is related to chronic GVHD and may reflect T cell expansion during chronic GVHD.


Interconversions and toxicity changes in hexachlorocyclohexane isomers on dispersion in water.
Studies on the transformations of hexachlorocyclohexane isomers, alpha-, beta-, gamma- and delta-, in aqueous solution were carried out at 25 +/- 1 degree C over a period of four weeks. Gas liquid chromatographic technique was used for analysis. The results indicated a loss as well as interconversion of all the four isomers with time. The resulting changes in toxicity of the aqueous solution were studied against Drosophila using topical application. Toxicity studies with aqueous solution of technical hexachlorocyclohexane were simultaneously carried out for comparison. Toxicity of the aqueous solutions of alpha-, beta-, and delta- isomers showed an increase while that of the gamma- isomer decreased significantly during the four week experimental period. Aqueous solution of technical HCH was equally toxic as that of the gamma- isomer initially and did not show much decrease in its toxicity at the end. Changes in toxicity of the individual isomer solutions were considered to be due, in part, to interconversions of HCH isomers.


Modifying dipalmitoylphosphatidylcholine monolayers by n-hexadecanol and dipalmitoylglycerol.
The monolayer structure of pure dipalmitoylphosphatidylcholine (DPPC) and equimolar mixtures of DPPC/n-hexadecanol (C(16)OH) and DPPC/dipalmitoylglycerol (DPG) are studied by the film balance technique and grazing incidence X-ray diffraction measurements. At 20 degrees C, the binary systems exhibit complete miscibility. In contrast to pure DPPC monolayers, a condensing effect is observed in the presence of both non-phospholipid additives; but the phase transition behavior differs. The tilt angle of the hydrocarbon chains in the DPPC/C(16)OH mixture is significantly smaller than in pure DPPC monolayers. The tilt of the chains is even further reduced in the mixed monolayer of DPPC/DPG. A comparison of the three systems reveals distinct structural features such as phase state, chain tilt, and molecular area over a wide range of surface pressures. Therefore, these monolayers provide a highly suitable model to investigate the influence of structural parameters on biological processes occurring at the membrane surface, e.g. enzymatic reactions and adsorption events.


The Effect of Dislocation Type (Crowe Types I-IV) on Pelvic Development in Developmental Dysplasia of the Hip: A Radiologic Study of Anatomy.
Classification of hip pathology in developmental dysplasia of the hip (DDH) helps in appropriate placement of implants during total hip arthroplasty. We examined preoperative unilateral and bilateral pelvic radiographs of 57 patients (114 hips) undergoing total hip arthroplasty because of DDH. Both sides of the pelvis were visually separated into 3 areas for comparison. When area ratios of hips with Crowe types II, III, and IV DDH were compared with ratios for healthy hips, values in hips with DDH were significantly low for the iliac wings, significantly high for the acetabular regions, and significantly low for the ischial area. Using a line crossing the healthy hip's teardrop and parallel to a line joining the distal sacroiliac joints is useful for calculating limb-length discrepancy.


A novel vitamin C analog, 2-O-(beta-D-Glucopyranosyl)ascorbic acid: examination of enzymatic synthesis and biological activity.
2-O-(beta-D-Glucopyranosyl)ascorbic acid (AA 2 beta G) isolated from a popular traditional Chinese food (Lycium fruit) was synthesized using cellulase derived from Trichoderma sp. with cellobiose as a glucose donor. 6-O-(beta-D-Glucopyranosyl)ascorbic acid as well as AA 2 beta G was also synthesized in this reaction. The vitamin C activity of AA 2 beta G was also evaluated using inherently scorbutic (osteogenic disorder Shionogi [ODS]) rats. The rats were fed vitamin C-deficient food and water containing AA 2 beta G for 21. AA 2 beta G supported their growth and the level of vitamin C in tissues was moderately maintained. The vitamin C level in some tissues depended on the hydrolytic activity of AA 2 beta G (beta-glucosidase activity) although the correlation was not statistically significant (P=0.08). The results indicate that AA 2 beta G has pro-vitamin C activity.


Cardiac application of embryonic stem cells.
Cardiomyocytes deceased during myocardial infarction (MI) are replaced with non-contractile scar tissue, which has a great chance to cause heart failure. Repair of dead or injured myocardium and improvement of cardiac function remain a serious challenge for the therapy of heart failure. Recently, stem cells have been transplanted in experimental settings to replace lost myocardium. This article summarizes the recent experimental findings on transplantation of embryonic stem cells (ESCs) and their derived cells in animals with myocardial injury and highlights the progresses in research of these particular cell types. Beneficial effects of cell transplantation with other cell types in injured hearts have been detailed in other reviews. ESCs are pluripotent cells derived from early mammalian embryos at the blasto-stage. These cells have the capacity for prolonged undifferentiated proliferation or differentiation into all of specialized somatic cell types of the body in culture, including cardiomyocytes. Because of the great ability of proliferation and differentiation to mature tissues, ESCs are a potential valuable resource for cell therapy targeting regeneration of functional myocardium in diseased hearts. In recent animal studies intramyocardial transplantation of ESCs or their differentiated cardiac-like cells regenerated injured myocardium and improved heart function in infarcted animal models. In addition, intravenous infusion of ESCs significantly increased the survival rate and attenuated myocardial injury in viral myocarditic mice. Development and characterization of cardiomyocytes in vitro from human ESCs have been reported recently. However, many ethical, political, and scientific barriers have to be overcome before clinical utilization of human ESCs and their differentiated cells for treating end-stage cardiac diseases.


An evaluation of cases of pneumonia that occurred secondary to hydrocarbon exposure in children.
Hydrocarbon pneumonia is distinct among the types of childhood pneumonia in that it has a different pathogenesis and treatment and is preventable. In this study, the cases of 54 children with hydrocarbon pneumonia admitted to the Dicle University Medical Faculty Pediatric Chest Diseases Unit between the years 2006 and 2010 were analyzed retrospectively. The medical records of 54 patients diagnosed with pneumonia after ingesting/inhaling hydrocarbons were analyzed retrospectively. Age, sex, presenting symptoms, clinical status, radiological and laboratory findings and response to treatment and prognosis were noted. 35 (64.8%) of the patients were male, 19 (35.2%) were female and the ages of the patients ranged from 1 to 5 with an average of 2.49 ± 0.80. The etiologies of the pneumonia were thinner (33%), naphta (3.7%) and kerosene. In 49 of the patients (90.7%), the symptoms started to occur the day the patient was exposed to hydrocarbons. The average length of hospital stay was 4.0 ± 2.3 days. Six patients were treated in the intensive care unit (ICU), and one patient with hydrocarbon pneumonia due to kerosene ingestion died. Inhaled corticosteroids were administered to 18 patients who were progressively deteriorating and inhaled salbutamol was given to 16 patients with bronchospasm. Patients with radiological findings on their chest X-rays and auscultatory findings were found to have longer hospital stays (p < 0.05). To prevent chemical pneumonia, precautions must be taken to stop children under 5 years of age from using/abusing chemical substances. Although some cases of chemical pneumonia lead to death, with diligent care and treatment, the outcomes are promising. The patients in this study group responded well to treatment with inhaled corticosteroids and salbutamol.


A reliable and efficient method for deleting operational sequences in PACs and BACs.
P1-derived artificial chromosomes (PACs) and bacterial artificial chromosomes (BACs) have become very useful as tools to study gene expression and regulation in cells and in transgenic mice. They carry large fragments of genomic DNA (> or =100 kb) and therefore may contain all of the cis-regulatory elements required for expression of a gene. Because of this, even when inserted randomly in the genome, they can emulate the native environment of a gene resulting in a tightly regulated pattern of expression. Because these large genomic clones often contain DNA sequences which can manipulate chromatin at the local level, they become immune to position effects which affect expression of smaller transgenes, and thus their expression is proportional to copy number. Transgenic mice containing large BACs and PACs have become excellent models to examine the regulation of gene expression. Their usefulness would certainly be increased if easy and efficient methods are developed to manipulate them. We describe herein a method to make deletion mutations reliably and efficiently using a novel modification of the Chi-stimulated homologous recombination method. Specifically, we generated and employed a Lox511 'floxed' CAM resistance marker that first affords selection for homologous recombination in Escherichia coli, and then can be easily deleted leaving only a single Lox511 site as the footprint.


[Assessment of malonyldialdehyde concentration as a product of lipid peroxidation and lipid metabolism in patients on chronic dialysis].
Chronic hemodialysis in patients with renal insufficiency is a factor significantly intensifying oxidative stress, resulting in increased lipid and lipoprotein peroxidation. It intensifies atherosclerotic activity. Malonyldialdehyde (MDA) concentration in serum, and isolated fraction of low density lipoprotein is indicators of lipid peroxidation intensification and therefore arteriosclerosis development. Assessment of MDA concentration as a product of lipid peroxidation and lipid metabolism in patients on chronic dialysis. The study included 48 dialyzed patients, age 22-68 undergoing chronic dialysis for, on average, 56 months. On account of dialysis period the patients were included into 3 subgroups: group 1 (n = 17) dialysis period 2 years, group 2 (n = 13) dialysis period 2-5 years and group 3 (n = 18) dialysis period longer than 5 years. Control group consisted of 30 healthy subjects. We assessed: malonyldialdehyde in serum and isolated fraction of low density lipids (LDL) and high density lipid (HDL) and cholesterol (CH) and triglycerides (TG), phospholipids (PL) in serum and isolated lipoprotein fractions. Significantly decreased levels of HDL, LDL fractions and increased triglicerides and elevated levels of MDA in serum and isolated LDL fraction were found in patients on chronic dialysis in comparison to control group (p < 0.05). Our results indicate apparent normalization of lipid metabolism in patients on chronic dialysis and suggest that MDA assessment is better marker for arteriosclerosis risk estimation in long-term dialyzed patients.


Sick in the head? Pathogen concerns bias implicit perceptions of mental illness.
Biases against the mentally ill are historically and cross-culturally pervasive, suggesting they may have an evolutionary basis. The prevailing view is that people seek to distance themselves from the mentally ill because they are perceived as dangerous, violent, and incompetent. However, because of similarities between sickness behaviors and symptoms of some mental disorders, it was hypothesized that mental illness stigma could be partially explained as a function of behavioral immune system biases designed to avoid potential sources of contagion. In two experiments, it was found that mental illness was implicitly associated more with disease than danger. In Experiment 1, this implicit association was exacerbated among people who have had their biological immune system activated by a recent illness. In Experiment 2, experimentally priming disease salience increased implicit association between mental illness and disease. Implications for the evolutionary origins of prejudice and the prevention of mental illness stigma are discussed.


Trans-1-chloro-2-fluoroethylene: microwave spectra and anharmonic force field.
For the first time the millimeter-wave spectra of the trans-35ClHC=CHF and trans-37ClHC=CHF isotopomers have been observed in natural abundance. Many DeltaJ=0, +/-1 DeltaK(-1)=+1 transitions for 35ClHC=CHF and DeltaJ=0 DeltaK(-1)=+1 transitions for 37ClHC=CHF have been detected and assigned. This allowed us to accurately determine the vibrational ground-state rotational constants, quartic and some sextic centrifugal distortion constants, and nuclear quadrupole coupling constants for both 35Cl and 37Cl. The experimental investigation has been supported by highly accurate theoretical predictions. As far as ab initio computations are concerned, the complete set of cubic and quartic force constants have been evaluated by numerical differentiation of the analytic second-order Møller-Plesset many-body perturbation theory/correlation consistent polarized valence triple zeta second derivatives. The anharmonic part of the force field completes the theoretical study on the equilibrium structure, dipole moment, chlorine quadrupolar tensor, and harmonic force field previously carried out by the same authors.


Obstetric antecedents for preterm delivery.
To investigate the obstetric antecedents for preterm delivery (PTD) in an Irish urban obstetric population, and to evaluate the incidence and outcome of such deliveries. A retrospective observational study of all preterm deliveries at the Rotunda Hospital, Dublin during the six-year period 1997-2002. The findings for early preterm deliveries (EPTD) (24+0-31+6 weeks' gestation), and late preterm deliveries (LPTD) (32+0-36+6 weeks' gestation) were analyzed separately. There were 38,795 deliveries after 24 weeks' gestation or >500 g birth weight, of which 2839 (7.3%) were preterm. Of all preterm deliveries, 626 (22.1%) were EPTD and 2213 (77.9%) were LPTD, resulting in an EPTD rate of 1.6% and an LPTD rate of 5.7%. Spontaneous unexplained preterm delivery accounted for 1221 (43.0%) of preterm deliveries (PTD), and of these 213 (34%) cases were EPTD and 1008 (45.5%) LPTD. The other most frequently observed obstetric causative factors, in order of importance, were multiple gestation (676; 23.8% of PTD), hypertensive disorders of pregnancy (243; 8.6%), antepartum hemorrhage (194; 6.8%), stillbirth (105; 3.7%), intrauterine growth restriction (53; 1.9%) and preterm prelabor rupture of membranes+/-chorioamnionitis (32; 1.1%). There were 75 early neonatal deaths among infants born prematurely, plus 105 stillbirths, resulting in a perinatal mortality rate of 63 per 1000 for PTD (n=180), which on subsequent analysis was 158 per 1000 for EPTD (n=99) and 37 per 1000 for LPTD (n=81). These data outline the obstetric factors linked to preterm delivery within a recent Irish urban obstetric population. Spontaneous idiopathic preterm labor was the principle causative factor in 43% of all preterm deliveries, and represents the proportion of women for whom future therapeutic intervention may be of benefit.


[Preclinical research of a new therapy for Gaucher's disease with F213I mutation].
To design and make trial of a new therapy for Gaucher disease. A substrate analogue of beta-Glc (glucocerebroside analogue, GCA) was used as a molecular chaperon. Normal and mutant skin fibroblasts were cultured with or without GCA. The activity of beta-Glc was assayed by fluorescent enzymologic techniques. The amount of beta-Glc was determined using Western blot. The beta -Glc was localized by double cell stain experiment. The degradation of glucocerebroside was assessed by thin layer chromatography (TLC) experiment using 14C-Serine. It was found that GCA could enhance the activity and amount of beta-Glc with F213I mutation. It also promoted the beta-Glc with F213I mutation to the lysosome and accelerated the degradation of glucocerebroside. The low molecular compound analogous to beta-Glc substrate (GCA ) may be a new therapeutic strategy for Gaucher's disease with F213I mutation.


Otologic Manifestations and Progression in Patients with Wegener's granulomatosis: A Survey in 55 Patients.
Granulomatosis with polyangiitis (GPA; also known as Wegener's granulomatosis) is a primary systemic vasculitis involving the ear, nose and throat system (ENT) and lower respiratory tract. Because of the lack of knowledge regarding the clinical findings of GPA due to the limited number of studies, the current study was designed to investigate the prevalence and nature of the otology manifestations in the disease course. In the current prospective study, patients with a diagnosis of GPA from 2012-2016 were included. A definitive diagnosis was made based on the history, physical examination (otomicroscopy, Rinne and Weber test), audiometry, tympanometry, cytoplasmic and perinuclear anti-neutrophil cytoplasmic antibody (C-ANCA and P-ANCA) investigations, and pathologic studies. Twenty-seven male and 28 female patients aged 41.6±15.3 years were enrolled. Ear involvement was found in 20 patients (36.3%), and the most prevalent symptom was loss of hearing followed by otalgia and tinnitus. Tinnitus improved in none of the patients. The most prevalent sign was otitis serous followed by mastoiditis and external otitis. The most important audiometry finding was sensorineural hearing loss. Pathological studies using pulmonary samples were more useful for diagnosis. Precise clinical examination is crucial for the early diagnosis of GPA. Otological manifestations are common, especially loss of hearing and otitis serous, and can be the first sign of this disease. Early diagnosis can lead to better treatment of Wegener's granulomatosis.


Evaluating the prognostic value of selected prognostic scales in patients operated on due to peritonitis.
The aim of the study was to assess the usefulness of prognostic scales: ASA (American Society of Anesthesiologist), MPI (Meinheim Peritonitis Index), MOFS (the Multiple Organ Failure Score) and SPI (the Simple Prognostic Index) in the prognosis of the course of disease in patients operated on for peritonitis. The study was conducted in the Clinical Department of General and Oncological Surgery of the Medical University in Łódź between January 2009 to December 2010. During this period 263 patients were operated on for peritonitis. Before surgery all patients were classified into particular groups according to the above mentioned prognostic scales according to their criteria. There were 29 (11%) deaths. ASA ≥4 (p<0.0001), MPI >30 (p<0.0001) MOFS ≥2 (p<0.0001), SPI II, III, IV (p<0.0001) were important risk factors of death. 1. ASA, MPI, MOFS and SPI scales are of high significance in predicting the outcome in patients operated on for peritonitis. 2. The ASA scale in spite and due to its simplicity is adequate enough to be used in everyday practice in patients operated on for peritonitis. 3. The MPI scale is most suitable in the scientific aims and in comparing the outcomes of patients operated on for peritonitis.


Tuberculosis and HIV-infection in developing countries.
Tuberculosis is a major public health problem in developing countries. In recent years, a (cost-)effective intervention has been developed in the national programmes of Tanzania and other developing countries. HIV transmission in populations with a high background prevalence of tuberculosis infection will increase the incidence of tuberculosis disease substantially. World Health Organization and World Bank are currently formulating new strategies to revitalise the global efforts against tuberculosis.


Neural network analysis of Chinese herbal medicine prescriptions for patients with colorectal cancer.
Traditional Chinese Medicine (TCM) is an experiential form of medicine with a history dating back thousands of years. The present study aimed to utilize neural network analysis to examine specific prescriptions for colorectal cancer (CRC) in clinical practice to arrive at the most effective prescription strategy. The study analyzed the data of 261 CRC cases recruited from a total of 141,962 cases of renowned veteran TCM doctors collected from datasets of both the DeepMedic software and TCM cancer treatment books. The DeepMedic software was applied to normalize the symptoms/signs and Chinese herbal medicine (CHM) prescriptions using standardized terminologies. Over 20 percent of CRC patients demonstrated symptoms of poor appetite, fatigue, loose stool, and abdominal pain. By analyzing the prescription patterns of CHM, we found that Atractylodes macrocephala (Bai-zhu) and Poria (Fu-ling) were the most commonly prescribed single herbs identified through analysis of medical records, and supported by the neural network analysis; although there was a slight difference in the sequential order. The study revealed an 81.9% degree of similarity of CHM prescriptions between the medical records and the neural network suggestions. The patterns of nourishing Qi and eliminating dampness were the most common goals of clinical prescriptions, which corresponds with treatments of CRC patients in clinical practice. This is the first study to employ machine learning, specifically neural network analytics to support TCM clinical diagnoses and prescriptions. The DeepMedic software may be used to deliver accurate TCM diagnoses and suggest prescriptions to treat CRC.


Dynamics and dissipation induced by single-electron tunneling in carbon nanotube nanoelectromechanical systems.
We demonstrate the effect of single-electron tunneling (SET) through a carbon nanotube quantum dot on its nanomechanical motion. We find that the frequency response and the dissipation of the nanoelectromechanical system to SET strongly depends on the electronic environment of the quantum dot, in particular, on the total dot capacitance and the tunnel coupling to the metal contacts. Our findings suggest that one could achieve quality factors of 10(6) or higher by choosing appropriate gate dielectrics and/or by improving the tunnel coupling to the leads.


A korean predictive model for postoperative nausea and vomiting.
Postoperative nausea and vomiting (PONV) is one of the most common and distressing complications after surgery. An identification of risk factors associated with PONV would make it easier to select specific patients for effective antiemetic therapy. We designed a case-controlled study to identify the risk factors for PONV in 5,272 surgical patients. At postoperative 2 and 24 hr, patients were visited and interviewed on the presence and severity of PONV. Thirty nine percent of patients experienced one or more episodes of nausea or vomiting. Five risk factors were highly predictive of PONV: 1) female, 2) history of previous PONV or motion sickness, 3) duration of anesthesia more than 1 hour, 4) non-smoking status, and 5) use of opioid in the form of patient controlled analgesia (PCA), in the order of relevance. The formula to calculate the probability of PONV using the multiple regression analysis was as follows: P (probability of PONV)=1/1+e(-Z), Z=-1.885+0.894 (gender)+0.661 (history)+0.584 (duration of anesthesia)+0.196 (smoking status)+0.186 (use of PCA-based opioid) where gender: female=1, male=0; history of previous PONV or motion sickness: yes=1, no=0; duration of anesthesia:more than 1 hr=1, less than or 1 hr=0; smoking status: no=1, yes=0; use of PCA-based opioid: yes=1, no=0.


Historical account: Francis William Aston: the man behind the mass spectrograph.
Francis William Aston was among the most accomplished physicists of the 20th century. A Nobel laureate and Fellow of the Royal Society, his research career spanned four decades. During this time, he provided experimental proof for the existence of isotopes of many of the chemical elements and recorded their masses using several, hand-built mass spectrographs. A rather private man who lived alone in Trinity College for much of his adult life, Aston remains a somewhat elusive and mysterious figure. This biography attempts to shed some more light on the man, including his character and his personal life, and particularly how his life was shaped by his childhood, environment and education. It contains previously unpublished material and photographs and complements the biographies of Hevesy and Thomson, following Aston's death, and that by Squires detailing the construction and performance of his mass spectrographs at the Cavendish Laboratory. It is published at a timely juncture, some 100 years after Aston's first arrival at Cambridge.


Surfactant proteins in innate host defense of the lung.
Surfactant proteins A and D (SP-A and SP-D) are members of the collectin family of host defense proteins that are expressed in epithelial cells lining the lung. SP-A and SP-D interact with surfactant lipids in complex ways to determine the structure of tubular myelin, and the ratio of surfactant subfractions that, in turn, influences surfactant uptake and metabolism, respectively. SP-A and SP-D play critical roles in host defense of the lung against diverse viral, fungal, and bacterial pathogens. The collectins bind to the surfaces of microbes via carbohydrate-dependent interaction, aggregating, opsonizing, and enhancing clearance of the organisms by alveolar macrophages in the lung. Pulmonary surfactant proteins A and D play dual roles in pulmonary homeostasis, determining the structure of alveolar lipids and mediating the innate host defense system of the lung.


An In Vitro Approach to Study Mitochondrial Dysfunction: A Cybrid Model.
Deficiency of the mitochondrial respiratory chain complexes that carry out oxidative phosphorylation (OXPHOS) is the biochemical marker of human mitochondrial disorders. From a genetic point of view, the OXPHOS represents a unique example because it results from the complementation of two distinct genetic systems: nuclear DNA (nDNA) and mitochondrial DNA (mtDNA). Therefore, OXPHOS defects can be due to mutations affecting nuclear and mitochondrial encoded genes. The groundbreaking work by King and Attardi, published in 1989, showed that human cell lines depleted of mtDNA (named rho0) could be repopulated by exogenous mitochondria to obtain the so-called "transmitochondrial cybrids." Thanks to these cybrids containing mitochondria derived from patients with mitochondrial disorders (MDs) and nuclei from rho0 cells, it is possible to verify whether a defect is mtDNA- or nDNA-related. These cybrids are also a powerful tool to validate the pathogenicity of a mutation and study its impact at a biochemical level. This paper presents a detailed protocol describing cybrid generation, selection, and characterization.


Decreased expression of ZO-1 is associated with tumor metastases in liver cancer.
Certain types of cancer exhibit downregulated expression of zonula occludens-1 (ZO-1), which serves an important function in tumor progression; however, the underlying molecular mechanisms that lead to this downregulation in cancer remain unclear. In the present study, the expression of ZO-1 in liver cancer (LC) tissues was investigated. Western blot and reverse transcription-quantitative polymerase chain reaction assays were used to detect the expression of ZO-1 protein and mRNA in LC tissues and paired adjacent non-tumorous tissues. The results indicated that, compared with non-tumorous tissues, the expression of ZO-1 was significantly downregulated at the protein (P<0.001) and mRNA (P=0.006) levels in LC tissue samples. In addition, various cellular and molecular methods were applied, including MTT, colony formation, flow cytometry and Transwell assays. The results indicated that overexpression of ZO-1 inhibited cell viability, proliferation and migration, and induced G0/G1 phase arrest in vitro.


Unresolved issues and current concepts in management of primary glomerulonephritis.
The successful treatment of primary glomerulonephritis (GN) presenting with nephrotic syndrome in adults depends heavily on an accurate diagnosis. A successful diagnosis depends on a correct approach, combining light microscopy, immunofluorescence, and other special staining of renal biopsy material examined by a trained nephropathologist. A good clinical history and serological tests easily rule out possible secondary causes (for example, infection, autoimmune, metabolic or toxic) in most cases. Unfortunately, these procedures are not put into practice in most cases in developing countries, resulting in missed diagnosis and unnecessary steroid and immunosuppressant therapy with its inherent morbidity. Following the emergence of IgA and IgM nephropathies as very common forms of glomerular disorders in some countries, immunofluorescence has become absolutely necessary for their diagnosis. Moreover, a recent meta-analysis has defined different treatment protocols for minimal change nephropathy, focal segmental glomerulosclerosis, membranous nephropathy, and IgA nephropathy for a better outcome. This article emphasizes and elaborates on these issues for proper management of primary GN.


Student led outreach workshops to promote basic life support.
To provide basic life support training to the staff, students and faculty of higher educational institutions in urban areas through pre-trained medical students, and to record the qualitative impact of community training on student facilitators. The mixed-method quasi-experimental study was conducted at the Foundation University, Islamabad, Pakistan, in collaboration with the Higher Education Commission of Pakistan from 2015 to 2018. Trained volunteer medical students were divided into teams to visit and provide hands-on basic life support training to 15 educational institutions in Rawalpindi and Islamabad with each batch having 45-50 participants. The participants completed pre- and post-training questionnaires, whereas the trainers went through post-training, semi-structured interviews. Quantitative analysis of pre and post-training responses was done using SPSS 21. Qualitative assessment of the impact of learning experience was done through constant comparative analysis of transcripts. There were 120 volunteers and 675 participants subjects. The participants' knowledge about basic life support showed significant improvement (p<0.001) post-training. There were two main recurring themes identified in the interviews; an opportunity to improve self-confidence, and technical skill. Hands-on training sessions conducted by pre-trained medical students not only resulted in an improvement in Basic Life Support knowledge of the participants, but also had a substantial impact on student trainers' self-confidence and technical skills.


Removal of focal segmental glomerulosclerosis (FSGS) factor suPAR using CytoSorb.
Treatment of primary focal segmental glomerulosclerosis (FSGS) and its recurrence after kidney transplantation associated with rapid deterioration of kidney function remains to be challenging despite advances in immunosuppressive therapy. The presence of circulating factors has been postulated to be a pivotal player in the pathogenesis of FSGS, although suPAR and CLCF-1 have been identified as the most promising causative factors. The potential therapeutic effect of suPAR elimination in an FSGS patient using CytoSorb, a hemoadsorption device that gained attention in the cytokine elimination in septic patients, was studied. Efficiency of total plasma exchange to remove suPAR was determined. CytoSorb hemoadsorption caused a 27.33% reduction of the suPAR level in a single treatment, whereas total plasma exchange showed a suPAR level reduction of 25.12% (n = 3; 95% confidence interval, 0.2777-0.8090; P < 0.01), which may indicate therapeutic potential in the treatment of primary FSGS and its recurrence in a kidney transplant.


[A chronobiological study of behavioral changes in rats].
A chronobiological study of behavioral changes in Wistar Kyoto rats (WKY), spontaneously hypertensive rats (SHR) and stroke prone spontaneously hypertensive rats (SHRSP) was undertaken. Attention was focused on changes in ambulatory activity and drinking behavior using an Ambulo-Drinkometer, the effects of centrally acting antihypertensive drugs, and the relationship between behavioral changes and humoral factors. (1) The experiment was performed during a light-dark alternation cycle. Approximately 10 days were required for rats to acclimate to new cages. (2) Using power spectral analysis, a 24 hr periodicity was dominant in both sexes of WKY and SHRSP. A 120 hr periodicity was demonstrated in female SHRSP. This long periodicity may have been due to a female sexual rhythm. (3) Ambulatory activity of WKY and SHRSP tended to decrease with age. (4) After abrupt cessation of clonidine administration, an ambulatory ultradian rhythm was demonstrated. Guanfacine treated SHR showed less change in ambulatory ultradian rhythm than clonidine treated SHR. (5) Using a Drinkometer with attached metabolic cages, drinking counts, urinary volumes, urinary aldosterone and catecholamine excretion rates were higher during the dark phase than during the light phase. It was demonstrated that analysis of rhythmicities and measurement of behavioral amplitude are both needed in the study of behavioral pharmacology.


Temporal progression of PARP activity in the Prph2 mutant rd2 mouse: Neuroprotective effects of the PARP inhibitor PJ34.
Peripherin (peripherin/rds) is a membrane-associated protein that plays a critical role in the morphogenesis of rod and cone photoreceptor outer segments. Mutations in the corresponding PRPH2 gene cause different types of retinal dystrophies characterized by a loss of photoreceptors. Over activation of poly-ADP-ribose polymerase (PARP) was previously shown to be involved in different animal models for hereditary retinal dystrophies. This includes the rd2 mouse, which suffers from a human homologous mutation in the PRPH2 gene. In the present study, we show that increased retinal PARP activity and poly-ADP-ribosylation of proteins occurs before the peak of rd2 photoreceptor degeneration. Inhibition of PARP activity with the well-characterized PARP inhibitor PJ34 decreased the levels of poly-ADP-ribosylation and photoreceptor cell death. These results suggest a causal involvement of PARP in photoreceptor degeneration caused by peripherin mutations and highlight the possibility to use PARP inhibition for the mutation-independent treatment of hereditary retinal dystrophies.


Treatment of Combined Freckles with Chloasma Using Q-Switched 1064 nm Laser.
The present study observed the therapeutic effect and possible side effects of Q-switch 1064-nm laser with large-spot and low-energy technology in the treatment of patients with combined freckles and chloasma. A Q1064-nm laser with a large-spot diameter of 6-8 mm, energy level of 2.0-3.3 J/cm2, frequency of 10 Hz, and pulse width of 10 ns was employed for the treatment. Each patient underwent treatment 10-15 times, with an interval of 10-15 days each time. Facial care was administered before and after treatment; attention was paid to cleaning and moisturizing, avoiding light, and using sunscreens strictly. The therapeutic effects were observed and evaluated. Freckles basically subsided (effective rate = 100%) and chloasma faded (effective rate = 39.4%). Furthermore, whitening and delicacy improvement were observed in the surrounding normal skin area. After laser treatment, confocal laser scanning microscopy revealed a large number of melanin particles in the upper part of the granular layer. Moreover, the amount of melanin in the middle and lower parts of the basal layer and spinous layer was significantly decreased. None of the patients developed postinflammatory pigmentation. In the treatment of freckles with chloasma, Q 1064-nm laser large-spot, low-energy technology not only removed freckles and faded chloasma but, most importantly, also reduced the incidence of postinflammatory pigmentation and improved patient satisfaction. This provided new methods and ideas for freckle laser treatment.


The diversity and extracellular enzymatic activities of yeasts isolated from water tanks of Vriesea minarum, an endangered bromeliad species in Brazil, and the description of Occultifur brasiliensis f.a., sp. nov.
The diversity of yeast species collected from the bromeliad tanks of Vriesea minarum, an endangered bromeliad species, and their ability to produce extracellular enzymes were studied. Water samples were collected from 30 tanks of bromeliads living in a rupestrian field site located at Serrada Piedade, Minas Gerais state, Brazil, during both the dry and rainy seasons. Thirty-six species were isolated, representing 22 basidiomycetous and 14 ascomycetous species. Occultifur sp., Cryptococcus podzolicus and Cryptococcus sp. 1 were the prevalent basidiomycetous species. The yeast-like fungus from the order Myriangiales, Candida silvae and Aureobasidium pullulans were the most frequent ascomycetous species. The diversity of the yeast communities obtained between seasons was not significantly different, but the yeast composition per bromeliad was different between seasons. These results suggest that there is significant spatial heterogeneity in the composition of populations of the yeast communities within bromeliad tanks, independent of the season. Among the 352 yeast isolates tested, 282 showed at least one enzymatic activity. Protease activity was the most widely expressed extracellular enzymatic activity, followed by xylanase, amylase, pectinase and cellulase activities. These enzymes may increase the carbon and nitrogen availability for the microbial food web in the bromeliad tank of V. minarum. Sequence analyses revealed the existence of 10 new species, indicating that bromeliad tanks are important sources of new yeasts. The novel species Occultifur brasiliensis, f.a., sp. nov., is proposed to accommodate the most frequently isolated yeast associated with V. minarum. The type strain of O. brasiliensis, f.a., sp. nov. is UFMG-CM-Y375(T) (= CBS 12687(T)). The Mycobank number is MB 809816.


Soluble narrow band gap and blue propylenedioxythiophene-cyanovinylene polymers as multifunctional materials for photovoltaic and electrochromic applications.
A family of soluble narrow band gap donor-acceptor conjugated polymers based on dioxythiophenes and cyanovinylenes is reported. The polymers were synthesized using Knoevenagel polycondensation or Yamamoto coupling polymerizations to yield polymers with molecular weights on the order of 10 000-20 000 g/mol, which possess solubility in common organic solvents. Thin film optical measurements revealed narrow band gaps of 1.5-1.8 eV, which gives the polymers a strong overlap of the solar spectrum. The energetic positions of the band edges were determined by cyclic voltammetry and differential pulse voltammetry and demonstrate that the polymers are both air stable and show a strong propensity for photoinduced charge transfer to fullerene acceptors. Such measurements also suggest that the polymers can be both p- and n-type doped, which is supported by spectroelectrochemical results. These polymers have been investigated as electron donors in photovoltaic devices in combination with PCBM ([6,6]-phenyl C(61)-butyric acid methyl ester) as an electron acceptor based on the near ideal band structures designed into the polymers. Efficiencies as high as 0.2% (AM1.5) with short circuit current densities as high as 1.2-1.3 mA/cm(2) have been observed in polymer/PCBM (1:4 by weight) devices and external quantum efficiencies of more than 10% have been observed at wavelengths longer than 600 nm. The electrochromic properties of the narrow band gap polymers are also of interest as the polymers show three accessible color states changing from an absorptive blue or purple in the neutral state to a transmissive sky-blue or gray in the oxidized and reduced forms. The wide electrochemical range of electrochromic activity coupled with the strong observed changes in transmissivity between oxidation states makes these materials potentially interesting for application to electrochromic displays.


Molecular Structure of P2Y Receptors: Mutagenesis, Modeling, and Chemical Probes.
There are eight subtypes of P2Y receptors (P2YRs) that are activated, and in some cases inhibited, by a range of extracellular nucleotides. These nucleotides are ubiquitous, but their extracellular concentration can rise dramatically in response to hypoxia, ischemia, or mechanical stress, injury, and release through channels and from vesicles. Two subclasses of P2YRs were defined based on clustering of sequences, second messengers, and receptor sequence analysis. The numbering system for P2YR subtypes is discontinuous; i.e., P2Y(1-14)Rs have been defined, but six of the intermediate-numbered cloned receptor sequences (e.g., P2y(3), P2y(5), P2y(7-10)) are not functional mammalian nucleotide receptors. Of these two clusters, the P2Y(12-14) subtypes couple via Gα(i) to inhibit adenylate cyclase, while the remaining subtypes couple through Gα(q) to activate phospholipase C. Collectively, the P2YRs respond to both purine and pyrimidine nucleotides, in the form of 5'-mono- and dinucleotides and nucleoside-5'-diphosphosugars. In recent years, the medicinal chemistry of P2Y receptors has advanced significantly, to provide selective agonists and antagonists for many but not all of the subtypes. Ligand design has been aided by insights from structural probing using molecular modelling and mutagenesis. Currently, the molecular modelling of the receptors is effectively based on the X-ray structure of the CXCR4 receptor, which is the closest to the P2Y receptors among all the currently crystallized receptors in terms of sequence similarity. It is now a challenge to develop novel and selective P2YR ligands for disease treatment (although antagonists of the P2Y(12)R are already widely used as antithrombotics).


Greenhouse gas and carbon profile of the u.s. Forest products industry value chain.
A greenhouse gas and carbon accounting profile was developed for the U.S. forest products industry value chain for 1990 and 2004-2005 by examining net atmospheric fluxes of CO(2) and other greenhouse gases (GHGs) using a variety of methods and data sources. Major GHG emission sources include direct and indirect (from purchased electricity generation) emissions from manufacturing and methane emissions from landfilled products. Forest carbon stocks in forests supplying wood to the industry were found to be stable or increasing. Increases in the annual amounts of carbon removed from the atmosphere and stored in forest products offset about half of the total value chain emissions. Overall net transfers to the atmosphere totaled 91.8 and 103.5 TgCO(2)-eq. in 1990 and 2005, respectively, although the difference between these net transfers may not be statistically significant. Net transfers were higher in 2005 primarily because additions to carbon stored in forest products were less in 2005. Over this same period, energy-related manufacturing emissions decreased by almost 9% even though forest products output increased by approximately 15%. Several types of avoided emissions were considered separately and were collectively found to be notable relative to net emissions.


Use of opioid analgesics in a patient with chronic abdominal pain.
Pethidine is the most commonly used opioid in hospitals in the UK, but it lacks potency, has a short duration of action and a narrow therapeutic index. These points are illustrated by a case history of a patient prescribed pethidine for chronic abdominal pain. Misplaced fears of the side-effects of morphine result in its underuse in the management of chronic pain with consequential restriction of patients' functional ability.


Microwave-assisted solvothermal synthesis of CuInSe2 chalcopyrites.
Chalcopyrite, CuInSe2 was prepared by a fast microwave-assisted solvothermal synthesis. The influence of reaction temperature, concentrations of the constituents, types of copper salts and added solvent on the morphology and crystallinity of the chalcopyrite has been investigated and also the optimized parameters are presented. The optimum crystallinity was obtained at 180 degrees C reaction temperature with 0.02 M of copper ion concentration. Interestingly, when the copper acetate was used as a copper source, particle size of chalcopyrite was dramatically reduced. Moreover, the synthesis at 1L scale of the reactants gave the particle size of 20 nm for CuInSe2 which is smaller than that of small scale synthesis (23-35 nm). XRD, SEM and Raman Spectroscopy techniques are used for characterization and evaluation of the morphology of the chalcopyrite.


Labeling of meridional and radial scans of the breast.
Meridional and radial scanning of the breast follows the anatomic planes of the breast. The scans at the 90 degrees and 180 degrees axes correspond to the lateral and cephalocaudal x-ray mammograms, respectively. Meridional scanning introduces unique problems of orientation and labeling. The labeling methods suggested in this paper result in comparable portions of each breast lying along identical planes of scan. An equation and a table that define the minimal angular increment required to detect a 0.5-cm lesion at the periphery of the breast are presented. Forms for converting meridional scans to orthogonal localization are also presented. In our hands, this method of labeling has proved to be simpler than that suggested by the American Institute of Ultrasound in Medicine.


Cucurbit[7]uril: an emerging candidate for pharmaceutical excipients.
Cucurbit[7]uril (CB[7]), belonging to the cucurbit[n]uril family (CB[n], n = 5-8, 10, or 13-15), may form host-guest complexes with a variety of small molecules of biomedical interest. The physical and chemical properties of the complexed drugs are often improved as a result of this complexation, suggesting the potential application of CB[7] as a pharmaceutical excipient. This review has summarized the most recent research progress reported between 2011 and early 2017 regarding the biocompatibility of CB[7] and the influence of CB[7] on the stability, solubility, biouptake, and biological activities (including therapeutic efficacies and toxicities) of guest drug molecules. Through this systemic summary and analysis, we intend to stimulate further research efforts in this area and promote the use of CB[7] as an emerging pharmaceutical excipient to improve various properties of drug molecules (or active pharmaceutical ingredients).


Review of state-of-the-art artificial compound eye imaging systems.
The natural compound eye has received much attention in recent years due to its remarkable properties, such as its large field of view (FOV), compact structure, and high sensitivity to moving objects. Many studies have been devoted to mimicking the imaging system of the natural compound eye. The paper gives a review of state-of-the-art artificial compound eye imaging systems. Firstly, we introduce the imaging principle of three types of natural compound eye. Then, we divide current artificial compound eye imaging systems into four categories according to the difference of structural composition. Readers can easily grasp methods to build an artificial compound eye imaging system from the perspective of structural composition. Moreover, we compare the imaging performance of state-of-the-art artificial compound eye imaging systems, which provides a reference for readers to design system parameters of an artificial compound eye imaging system. Next, we present the applications of the artificial compound eye imaging system including imaging with a large FOV, imaging with high resolution, object distance detection, medical imaging, egomotion estimation, and navigation. Finally, an outlook of the artificial compound eye imaging system is highlighted.


[Harlequin syndrome].
Harlequin syndrome is an autonomic syndrome of heat, emotion and exercise induced flushing and sweating limited to one side of the face in combination with impairment of sweating and flushing on the contralateral side, Two women aged 32 and 39 years displayed this syndrome. In one patient no other neurological symptoms were found; MRI of cervicothoracic spine failed to disclose a structural lesion. The second patient had four years before presented with a Horner's syndrome on the contralateral side, where MRI now disclosed a tumour located in the paravertebral thoracic region at the apex of the lung.


The [2 + 1] and [4 + 3] cyclization reactions of fulvenes with Fischer carbene complexes: new access to annulated cyclopentanones.
Pentafulvenes are regioselectively cyclopropanated with group 6 Fischer carbene complexes leading to the homofulvene ring with complete endo selectivity. The homofulvene adducts undergo in turn a further cyclopropanation with ethyl diazoacetate or cyclopentannulation with a Fischer alkenyl carbene complex to provide substituted cyclopentanones after ozonolysis of the exocyclic carbon=carbon double bond. Fischer alkynyl carbene complexes also produce the corresponding alkynyl homofulvenes, albeit the exo stereoisomer is in this case exclusively or preferentially formed. Under moderate CO pressure, tungsten alkynyl carbene complexes cycloadd to pentafulvenes in a [4 + 3] fashion, giving rise to bicyclo[3.2.1]octadien-2-ones.