Relationship between ventilatory expired gas and cardiac parameters during symptom-limited exercise testing in patients with heart failure.
This study investigates the relationship between ventilatory expired gas and cardiac parameters measured during exercise testing in patients with heart failure. Twenty-five subjects (12 male, 13 female) diagnosed with compensated heart failure underwent symptom-limited exercise testing with ventilatory expired gas analysis. Metabolic and cardiac measures of interest were collected during testing. Mean peak oxygen consumption (VO2), minute ventilation/carbon dioxide production (VE/VCO2) slope, percentage of age predicted maximal heart rate achieved during exercise testing (%APMHR), and peak respiratory exchange ratio were 14.7 +/- 4.7 mL O2/kg/min-1, 33.8 +/- 9.8, 76% +/- 15%, and 1.1 +/- 0.11, respectively. The VE/VCO2 slope was significantly correlated with the following: %APMHR (r = -0.81, P < 0.001), peak VO2 (r = -0.83, P < 0.001), VO2 at ventilatory threshold (r = -0.70, P < 0.001), and the dead space to tidal volume ratio (VD/Vt) (r = 0.65, P < 0.001). The ability of peak VO2 and %APMHR to predict the VE/VCO2 slope was significant (r = 0.86, r2 = 0.72, P < 0.0001). This study demonstrates the importance of analyzing multiple exercise test parameters, including metabolic measures, in patients with heart failure.


[A Case of Neoadjuvant Chemotherapy with Modified FOLFOXIRI plus Bevacizumab for Transverse Colon Cancer with Invasion of the Gastric Antrum].
A 66-year-old male diagnosed with transverse colon cancer was admitted to our hospital. Computed tomography, colonoscopy, and esophagogastroduodenoscopy revealed locally advanced cancer with invasion of the gastric antrum. We staged the disease as cT4a, cN2, cM0, Stage ⅢB, with wild-type RAS expression. We performed an ileostomy prior to administering chemotherapy. The patient received 4 courses of modified FOLFOXIRI plus bevacizumab and 2 courses of FOLFIRI. The size of the tumor noticeably decreased after chemotherapy. The patient experienced grade 3 neutropenia, anorexia, and oral mucositis during chemotherapy. We performed a right hemicolectomy(D3), partial gastrectomy and ileum resection after administering neoadjuvant chemotherapy. The pathological stage of the disease was ypT2, ypN0, ypM0, ypStageⅠ, and the effect of the chemotherapy was Grade 1b. After the resection, he received mFOLFOX6 and CapeOX for 3 months as adjuvant chemotherapy. He remained cancer-free for 1 year and 3 months after the surgery. This result suggests that preoperative modified FOLFOXIRI plus bevacizumab chemotherapy is a useful regimen for the treatment of locally advanced colon cancer.


The peripheral cannabinoid receptor: adenylate cyclase inhibition and G protein coupling.
Two cannabinoid receptors, designated neuronal (or CB1) and peripheral (or CB2), have recently been cloned. Activation of CB1 receptors leads to inhibition of adenylate cyclase and N-type voltage-dependent Ca2+ channels. Here we show, using a CB2 transfected Chinese hamster ovary cell line, that this receptor binds a variety of tricyclic cannabinoid ligands as well as the endogenous ligand anandamide. Activation of the CB2 receptor by various tricyclic cannabinoids inhibits adenylate cyclase activity and this inhibition is pertussis toxin sensitive indicating that this receptor is coupled to the Gi/G(o) GTP-binding proteins. Interestingly, contrary to results with CB1, anandamide did not inhibit the CB2 coupled adenylate cyclase activity and delta 9-tetrahydrocannabinol had only marginal effects. These results characterize the CB2 receptor as a functional and distinctive member of the cannabinoid receptor family.


Lipid alterations in lipid rafts from Alzheimer's disease human brain cortex.
Lipid rafts are membrane microdomains intimately associated with cell signaling. These biochemical microstructures are characterized by their high contents of sphingolipids, cholesterol and saturated fatty acids and a reduced content of polyunsaturated fatty acids (PUFA). Here, we have purified lipid rafts of human frontal brain cortex from normal and Alzheimer's disease (AD) and characterized their biochemical lipid composition. The results revealed that lipid rafts from AD brains exhibit aberrant lipid profiles compared to healthy brains. In particular, lipid rafts from AD brains displayed abnormally low levels of n-3 long chain polyunsaturated fatty acids (LCPUFA, mainly 22:6n-3, docosahexaenoic acid) and monoenes (mainly 18:1n-9, oleic acid), as well as reduced unsaturation and peroxidability indexes. Also, multiple relationships between phospholipids and fatty acids were altered in AD lipid rafts. Importantly, no changes were observed in the mole percentage of lipid classes and fatty acids in rafts from normal brains throughout the lifespan (24-85 years). These indications point to the existence of homeostatic mechanisms preserving lipid raft status in normal frontal cortex. The disruption of such mechanisms in AD brains leads to a considerable increase in lipid raft order and viscosity, which may explain the alterations in lipid raft signaling observed in AD.


Kentucky pilot project for primary PCI without onsite CABG.
The American College of Cardiology, the American Heart Association, and the Society for Cardiovascular Angiography and Interventions strongly recommend that primary Percutaneous Coronary Intervention (PCI) should be performed in facilities that have an experienced cardiovascular surgical team available as emergency backup for all procedures. The current study investigates the medical soundness of allowing select facilities in Kentucky to perform primary PCI despite being devoid of onsite emergency backup capabilities. Two hospitals in the state of Kentucky, currently without emergency backup capabilities, have been allowed to perform primary PCIs for more than three years (beginning in April 2005) by the Kentucky Cabinet for Health and Family Services. The two hospitals selected were of similar size (approximately 200 beds) and similar distances from hospitals with onsite emergency backup capabilities (approximately one hour). We performed an analysis evaluating if hospitals without backup surgical capability have similar outcomes when compared to hospitals with backup surgical capabilities. Outcome variables included: (1) mortality, (2) cardiac arrest as result of PCI, (3) emergency surgery performed as a result of PCI, and (4) door-to-balloon time. Our results suggest that there is no significant difference in any of the outcome variables studied between facilities with and without onsite emergency backup capabilities. Recommendations concerning primary PCI may need to be revisited. The principal outcomes associated with primary PCI were not significantly affected by whether a facility has onsite emergency backup capabilities. Therefore, we recommend that hospitals without backup surgical capabilities be allowed to perform primary PCI (with restrictions based on surgeon experience and the facilities' volume).


The effect of sex on ventricular arrhythmic events in patients with congestive heart failure.
The propensity to develop specific arrhythmias varies between the sexes. Patients with congestive heart failure (CHF) have a high prevalence of ventricular ectopy. However, it is not known if sex related differences exist in the susceptibility to arrhythmias in the setting of CHF. The study population included 159 men and 77 women (mean age 61 +/- 14 years) admitted for decompensated CHF. The severity of atrial and ventricular arrhythmias was assessed by 24-hour Holter monitoring. None of the patients were on parenteral vasoactive therapy during Holter recording. All measures of ventricular ectopy were markedly lower in women compared to men. The mean hourly ventricular pairs (283 +/- 67 vs 106 +/- 30, P = 0.04), mean hourly repetitive ventricular beats (28 +/- 7 vs 10 +/- 3, P = 0.04), and the frequency of ventricular tachycardia episodes per 24 hours (31 +/- 9 vs 7 +/- 3, P = 0.01) were significantly lower in women. After inclusion of clinical variables and drug therapies in a multivariate analysis, the negative relationship between female sex and the frequency of ventricular pairs (P = 0.04), repetitive ventricular beats (P = 0.04), and ventricular tachycardia episodes (P = 0.0005) remained independent. No differences in atrial ectopy between men and woman were found. Complex ventricular ectopy and episodes of ventricular tachycardia are significantly lower in women with CHF. Whether these finding are relevant to female survival advantage in the setting of heartfailure can only be determined by a prospective study. Further understanding of the mechanisms involved in the protection conferred by the patient's sex would advance our understanding about arrhythmias in heart failure.


Effect of HbE heterozygosity on the measurement of HbA1c.
Measurement of HbA1c provides an excellent measure of glycaemic control for diabetic patients. However, haemoglobin (Hb) variants are known to interfere with HbA1c analysis. In our laboratory HbA1c measurement is performed by Variant II turbo 2.0. The aim of this study is to investigate the influence of HbE trait on HbA1c analysis. Haemoglobin variants were identified by HbA1c analysis in 93 of 3522 samples sent to our laboratory in a period of 1 month. Haemoglobin analysis identified HbE trait in 81 of 93 samples. To determine the influence of HbE trait on HbA1c analysis by Variant II Tubo 2.0, boronate affinity high performance liquid chromatography (HPLC) method (Primus PDQ) was used as the comparison method. Two stage linear regression analysis, Bland Altman plot and Deming regression analysis were performed to analyse whether the presence of HbE trait produced a statistically significant difference in the results. The total allowable error for HbA1c by the Royal Australasian College of Pathologists (RCPA) external quality assurance is 5%. Hence clinically significant difference is more than 5% at the medical decision level of 6% and 9%. Statistically and clinically significant higher results were observed in Variant II Turbo 2.0 due to the presence of HbE trait. A positive bias of ∼10% was observed at the medical decision levels. Laboratories should be cautious when evaluating HbA1c results in the presence of haemoglobin variants.


A randomized controlled trial of hepatectomy with adjuvant transcatheter arterial chemoembolization versus hepatectomy alone for Stage III A hepatocellular carcinoma.
Hepatectomy is considered as the potentially curative treatment for hepatocellular carcinoma (HCC) and used in some selected Stage IIIA HCC, which include multiple tumors more than 5 cm or tumor involving a major branch of the portal or hepatic vein(s) (UICC TNM staging system, sixth edition). Transcatheter arterial chemoembolization (TACE) was used in retrospective studies to improve the survival outcome of resected HCC. However, its beneficial effect on the survival outcomes of the Stage IIIA patients has not been evaluated. The present study is to evaluate if hepatectomy combining with adjuvant TACE for Stage IIIA HCC result in better long-term survival outcome when compared with hepatectomy alone. From January 2001 to March 2004, we conducted a prospective randomized trial in patients with Stage IIIA HCC (NCT00652587), recruiting 115 Stage IIIA HCC patients to undergo hepatectomy with adjuvant TACE (HT arm) or to undergo hepatectomy alone (HA arm) in our cancer center. Survival outcomes of the two arms were analyzed. The demographic data were well matched between the two arms. There were no significant differences in the morbidity and in-hospital mortality between the two arms of patients. The most significant toxicities associated with adjuvant TACE were nausea/vomiting (54.4%) and transient hepatic toxicity (elevation of aminotransferase, 52.6%). Although there was no significant difference in the rate of recurrence between the two arms (50/57 vs. 56/58, P = 0.094), HT arm seemed to have more proportion of single lesion of recurrent HCC (chi (2) = 3.719, P = 0.054) and more proportion of potential curative therapy for recurrence (chi (2) = 4.456, P = 0.035). Until the time of censor, 92 patients had died. The 1-, 3-, and 5-year overall survival rates and median overall survival for HT arm were 80.7, 33.3, 22.8% and 23.0 months, respectively. The corresponding overall survival rates and median overall survival for HA arm were 56.5, 19.4, 17.5% and 14.0 months, respectively. The difference was significant (stratified log-rank test, P = 0.048). The 1-, 3-, and 5-year disease-free survival rates and median disease-free survival for HT arm were 29.7, 9.3, 9.3% and 6.0 months, respectively; correspondingly, for HA arm were 14.0, 3.5, 1.7% and 4.0 months, respectively (stratified log-rank test, P = 0.004). For Stage IIIA HCC, hepatectomy with adjuvant TACE efficaciously and safely improved survival outcomes when compared with hepatectomy alone.


Dental caries experience of children in Northland/Te Tai Tokerau.
To describe the prevalence, severity and intra-oral distribution of dental caries among children from four Northland communities. Cross-sectional epidemiological survey of a Census sample. Dental examinations were systematically conducted on all children aged 5 or 6 and all children 12 or 13 (and for whom parental consent was obtained) in Kaitaia, Kaikohe, Kawakawa/Moerewa and Dargaville. Bitewing radiography was used to aid caries diagnosis in the older age group. Data are reported for the deciduous dentition in the 5-6-year-olds, and the permanent dentition in the 12-13-year-olds. There were 369 5-6-year-olds and 171 12-13-year-olds, approximately two-thirds of whom were Maori. Almost 88% of 5-6-year-olds had experienced dental caries, and this was lower among the Pakeha/Other group, those attending higher-decile schools, and those from Dargaville. Overall caries experience (represented by a mean dmft score of 5.6; sd 3.9) was higher among Maori children, those attending lower-decile schools, and those from Kaikohe, Kawakawa/ Moerewa or Kaitaia, as was the number of untreated decayed surfaces. Almost one in four children had lost at least one tooth due to caries, and this was higher among Maori children and those from schools in more deprived areas, and lower among children from Dargaville. Caries experience was greatest among the second molars in either arch, and lowest among the mandibular incisors. Among the 12-13-year-olds, 85% had experienced dental caries (mean DMFT = 3.7; sd 3.1). The number of untreated surfaces with decay (more than 3, on average) was considerably lower among children from Dargaville. Caries experience was greatest among the first molars in either arch (followed by the second premolars), and absent among the mandibular incisors. The prevalence and severity of dental caries in Northland is very high in comparison to the rest of New Zealand. The problem is particularly acute among northern communities and Maori. Dealing with the problem will require a combination of population health and personal health interventions.


Feynman-Kac formula for stochastic hybrid systems.
We derive a Feynman-Kac formula for functionals of a stochastic hybrid system evolving according to a piecewise deterministic Markov process. We first derive a stochastic Liouville equation for the moment generator of the stochastic functional, given a particular realization of the underlying discrete Markov process; the latter generates transitions between different dynamical equations for the continuous process. We then analyze the stochastic Liouville equation using methods recently developed for diffusion processes in randomly switching environments. In particular, we obtain dynamical equations for the moment generating function, averaged with respect to realizations of the discrete Markov process. The resulting Feynman-Kac formula takes the form of a differential Chapman-Kolmogorov equation. We illustrate the theory by calculating the occupation time for a one-dimensional velocity jump process on the infinite or semi-infinite real line. Finally, we present an alternative derivation of the Feynman-Kac formula based on a recent path-integral formulation of stochastic hybrid systems.


United Nations/Burma Programme for Drug Abuse Control. The first phase: 1976 to 1981.
The paper provides an outline of a wide-ranging drug abuse control programme undertaken by the Government of the Socialist Republic of the Union of Burma with support and assistance from the United Nations. The components included law enforcement, crop substitution, measures for treatment and rehabilitation and a nationwide programme for drug education. The overall effort was co-ordinated by the Ministry of Home and Religious Affairs, through a Central Committee for Drug Abuse Control on which the Deputy Ministers of the Ministries concerned were members. Liaison between the executing Burmese agencies and the United Nations assisting organizations was effected through a small United Nations office established in Rangoon. The promising result of the programme has led to a further Agreement between the government and the United Nations for the continuation of the programme for a further five years from May 1981.


Can parents prevent heavy episodic drinking by allowing teens to drink at home?
The current study examined whether permitting young women to drink alcohol at home during senior year of high school reduces the risk of heavy drinking in college. Participants were 449 college-bound female high school seniors, recruited at the end of their senior year. Participants were classified into one of three permissibility categories according to their baseline reports of whether their parents allowed them to drink at home: (a) not permitted to drink at all; (b) allowed to drink with family meals; (c) allowed to drink at home with friends. Repeated measures analysis of variance was used to compare the drinking behaviors of the three groups at the time of high school graduation and again after the first semester of college. Students who were allowed to drink at home during high school whether at meals or with friends, reported more frequent heavy episodic drinking (HED) in the first semester of college than those who reported not being allowed to drink at all. Those who were permitted to drink at home with friends reported the heaviest drinking at both time points. Path analysis revealed that the relationship between alcohol permissiveness and college HED was mediated via perceptions of parental alcohol approval.


'A way of struggle': reformations and affirmations of E. P. Thompson's class analysis in the light of postmodern theories of language.
This paper is an analysis of the role of language in historical class formation in light of the recent developments in postmodern social theory and historiography. Revisionists from within this perspective have questioned if not abandoned E. P. Thompson's class struggle analysis, arguing that he fails to account for the constitutive character of language in the construction of collective identities. They oppose his account of the making of the English working class with alternative histories emphasizing populist and other non-class identities. Drawing on the Bakhtin Circle of literary studies, and returning to Thompson's own writings, I argue that we can incorporate language into class struggle analysis as a critical mediating force. I maintain that class struggle occurs largely within a hegemonic discursive formation, and that class consciousness and identity thus in part are formed through counter-hegemonic strategies of resistance to ideological domination. To illustrate this theory I analyse the role of language in the class struggles of the silk weavers of the Spitalfields district in London in the 1820s. I analyse how the silk weavers articulated a class consciousness through their counter-hegemonic struggles with the large capitalists and the language of political economy.


Tumor infiltration by FcγRIII (CD16)+ myeloid cells is associated with improved survival in patients with colorectal carcinoma.
The prognostic significance of macrophage and natural killer (NK) cell infiltration in colorectal carcinoma (CRC) microenvironment is unclear. We investigated the CRC innate inflammatory infiltrate in over 1,600 CRC using two independent tissue microarrays and immunohistochemistry. Survival time was assessed using the Kaplan-Meier method and Cox proportional hazards regression analysis in a multivariable setting. Spearman's rank correlation tested the association between macrophage and lymphocyte infiltration. The Basel study included over 1,400 CRCs. The level of CD16+ cell infiltration correlated with that of CD3+ and CD8+ lymphocytes but not with NK cell infiltration. Patients with high CD16+ cell infiltration (score 2) survived longer than patients with low (score 1) infiltration (p = 0.008), while no survival difference between patients with score 1 or 2 for CD56+ (p = 0.264) or CD57+ cell (p = 0.583) infiltration was detected. CD16+ infiltrate was associated with improved survival even after adjusting for known prognostic factors including pT, pN, grade, vascular invasion, tumor growth and age [(p = 0.001: HR (95% CI) = 0.71 (0.6-0.9)]. These effects were independent from CD8+ lymphocyte infiltration [(p = 0.036: HR (95% CI) = 0.81 (0.7-0.9)] and presence of metastases [(p = 0.002: HR (95% CI) = 0.43 (0.3-0.7)]. Phenotypic studies identified CD16+ as CD45+CD33+CD11b+CD11c+ but CD64- HLA-DR-myeloid cells. Beneficial effects of CD16+ cell infiltration were independently validated by a study carried out at the University of Athens confirming that patients with CD16 score 2 survived longer than patients with score 1 CRCs (p = 0.011). Thus, CD16+ cell infiltration represents a novel favorable prognostic factor in CRC.


Multiple interactions of complement Factor H with its ligands in solution: a progress report.
Factor H (FH) is the major regulator of the central complement protein C3b in the alternative pathway of complement activation, and is comprised of 20 SCR domains. A FH Tyr402His polymorphism in SCR-7 is associated with age-related macular degeneration (AMD) and leads to deposition of complement in drusen. The unravelling of how FH interacts with five major physiological and patho-physiological ligands is complicated by the weak nature of these interactions, coupled with the multivalency of FH. Using multiple biophysical methods, we summarise our recent results for these five FH ligands: (1) FH by itself shows a folded-back SCR domain structure in solution, and self-associates in a manner dependent on electrostatic forces. (2) FH activity is inhibited by zinc, which causes FH to aggregate. The onset of FH-zinc aggregation for zinc concentrations above 20 muM appears to be enhanced with the His402 allotype, and may be relevant to AMD. (3) The FH and C-reactive protein (CRP) interaction has been controversial; however our new work resolves earlier discrepancies. The FH-CRP interaction is only observed when native CRP is at high acute-phase concentration levels, and CRP binds weakly to the His402 FH allotype to suggest a molecular mechanism that leads to AMD. (4) Heparin is an analogue of the polyanionic host cell surface, and FH forms higher oligomers with larger heparin fragments, suggesting a mechanism for more effective FH regulation. (5) The interaction of C3b with FH also depends on buffer, and FH forms multimers with the C3d fragment of C3b. This FH-C3d interaction at high FH concentration may also facilitate complement regulation. Overall, our results to date suggest that the FH interactions involving zinc and native CRP have the closest relevance for explaining the onset of AMD.


Influence of the N-linked oligosaccharides on the biosynthesis, intracellular routing, and function of the human asialoglycoprotein receptor.
The human asialoglycoprotein receptor (ASGP-R) is a membrane glycoprotein of 46,000 Da which possesses two N-linked oligosaccharide chains (Schwartz, A. L., and Rup, D. (1983) J. Biol. Chem. 258, 11249-11255). In order to examine the role of N-linked oligosaccharides in the biosynthesis, intracellular routing, and function of the ASGP-R, we have used Hep G2 cells, which have a large number of ASGP-R, and two inhibitors of glycosylation, swainsonine and tunicamycin. In the presence of swainsonine, newly synthesized ASGP-R is a 43,000-Da species which is endoglycosidase H-sensitive, appears on the Hep G2 cell surface, and specifically binds 125I-asialoorosomucoid (ASOR). In the presence of tunicamycin newly synthesized ASGP-R is a 34,000-Da nonglycosylated species which appears on the Hep G2 cell surface where it specifically binds 125I-ASOR. There is no major effect on subsequent uptake and degradation of 125I-ASOR in cells whose ASGP-R was synthesized in the presence of tunicamycin. The turnover of ASGP-R synthesized in the presence of either swainsonine or tunicamycin is not significantly altered from that found for the normal 46,000-Da species. Thus, it appears that the two N-linked oligosaccharide chains of the human ASGP-R do not play a major role in the intracellular routing, turnover, or function of ASGP-R.


Direct invasion to the colon by hepatocellular carcinoma: report of two cases.
Although hepatocellular carcinoma (HCC) is a common tumor, direct invasion of the gastrointestinal tract by HCC is uncommon. Recently, we encountered two cases of HCC with direct invasion to the colon. The first patient was a 79-year-old man who underwent transarterial chemo-embolization (TACE) for HCC 1.5 years prior to admission to our hospital. Computed tomography (CT) showed a 7.5-cm liver tumor directly invading the transverse colon. Partial resection of the liver and transverse colon was performed. The patient survived 6 mo after surgery, but died of recurrent HCC. The second patient was a 69-year-old man who underwent TACE and ablation for HCC 2 years and 7 months prior to being admitted to our hospital for melena and abdominal distension. CT revealed a 6-cm liver tumor with direct invasion to the colon. The patient underwent partial resection of the liver and right hemicolectomy. The patient recovered from the surgery. But, unfortunately, he died of liver failure due to liver cirrhosis one month later. Although the prognosis of HCC that has invaded the colon is generally poor due to the advanced stage of the disease, surgical resection may be a favorable treatment option in patients with a good general condition.


Mutagenicity of hydralazine in mammalian cells and bacteria.
The genotoxicity of hydralazine (HDZ), an antihypertensive agent, was evaluated in mammalian cells and bacteria. The formation of mutants at the hypoxanthine guanine phosphoribosyl transferase locus in an adult rat liver cell line ARL 18 was determined. Bacterial mutagenicity was assessed in Salmonella typhimurium strains TA100 and TA102. The latter strain was chosen because it has A:T bases at the reversion site and HDZ has been reported to interact with thymidine. HDZ was mutagenic to ARL 18 cells with a concentration-dependent increase in mutants observed at 5 x 10(-6) to 5 x 10(-4) M. At 5 x 10(-4) M HDZ, there were 110 mutants/10(6) colony-forming cells compared to 129 for cells exposed to 10(-4) M benzo(a)pyrene, a known genotoxin. Bacterial mutants were observed with HDZ in both strains in the absence of an activating system. HDZ also induced mutants in the presence of S-9 from Aroclor-induced rat liver or uninduced rabbit liver. These results were consistent with previous reports of the mutagenicity of HDZ in TA100 and extend the observations to TA102, a strain designed to detect oxidative damage. This study also provides the first evidence of the mutagenicity of HDZ in mammalian cells. These data support the genotoxicity of HDZ in in vitro systems.


TiO2@CeOx core-shell nanoparticles as artificial enzymes with peroxidase-like activity.
The Ce4+↔Ce3+ redox switch is at the basis of an all-inorganic catalytic cycle that is capable of mimicking the activity of several natural redox enzymes. The efficiency of these artificial enzymes (nanozymes) strongly depends on the Ce4+/Ce3+ ratio. By capitalizing on the results obtained on oxide/oxide model systems, we implemented a simple and effective procedure to obtain conformal TiO2@CeOx core-shell nanoparticles whose thickness is controlled with single-layer precision. Since the Ce3+ species are stabilized only at the interface by the electronic hybridization with the TiO2 states, the modulation of the shell thickness offers a simple method to tailor the Ce4+/Ce3+ ratio and therefore the catalytic properties. The activity of these nanoparticles as artificial peroxidase-like enzymes was tested, showing exceptional performances, even better than natural horseradish peroxidase enzyme. The main advantage with respect to other oxide/oxide nanozymes is that our nanoparticles, having a tunable Ce4+/Ce3+ ratio, are efficient already at low H2O2 concentrations.


Neurogenic and antineurogenic effects from modifications at the Notch locus.
The best studied mutations at the Notch locus produce a neurogenic phenotype, with a massive overgrowth of the nervous system at the expense of epidermis. We report here that, in the development of the adult peripheral nervous system, the Abruptex alleles of Notch have the opposite phenotype, namely an underproduction of sensory organs or sensilla. This arises primarily not from an arrest of the lineages that produce sensilla, from the degeneration of sensillar cells, or from the transformation into neurons of cells that normally secrete the cuticular components of a sensillum (as can happen in Notch alleles). Rather, our evidence argues strongly that the sensillar mother cells never form. This implies that the Notch protein plays a role in the process that first generates a difference between sensillar mother cells and ordinary epidermal cells. The number of sensilla formed on the wing of flies carrying multiple doses of Notch+ is virtually the same as that of wild type, i.e. the Abruptex phenotype is not reproduced to any significant extent. This suggests that the single amino acid substitutions that occur in Abruptex mutants confer on the protein some functionally distinctive feature, possibly more powerful intermolecular binding or altered stability.


Monoclonal anti-VH141 antibodies that specifically recognize the heavy chain variable region of, and are closely related to, MOPC141 myeloma protein whose VH gene belongs to VHQ52 family.
To raise monoclonal antibodies that specifically recognize the heavy chain variable region of MOPC141 myeloma protein (VH141), which belongs to VHQ52 family, rats were immunized with Fd'-conjugated keyhole limpet haemocyanin (KLH) (Fd': Fd' fragments of MOPC141), and the spleen cells were fused with mouse myeloma cells. The resulting 900 hybridomas were screened for antibody activity against Fd'1 fragments having no constant H-chain sequences, which were prepared by cleavage of the Fd' fragments with cyanogen bromide, and two monoclonal antibodies, designated 3-2-7h and 3-5-6f, were obtained. Radioimmunoassay inhibition test showed that the two monoclonal antibodies specifically recognized the VH141, but each was directed to a different determinant on the VH141. When the functional VH gene of Abelson virus-transformed mu-producing pre-B cells, which could be strongly stained with 3-5-6f monoclonal antibody, was cloned and sequenced, the VH gene was closely relate to that of MOPC141 (88% and 94% homology at amino acid and DNA level, respectively). Taken together, the results indicated that 3-2-7h had high specificity only for the VH141, whereas 3-5-6f specifically reacted not only with the VH141 but also with the VH region closely related to that of MOPC141, and that both the monoclonal anti-VH141 antibodies were specific for a limited range of VH regions within the VHQ52 family rather than being VHQ52 family specific. These monoclonal anti-VH141 antibodies should be very useful to determine at a single cell level by immunofluorescence the usage of the VH gene(s) identical or closely related to that of MOPC141 during early B-cell development.


Cell-free and cell-bound hemolytic activities of Proteus penneri determined by different Hly determinants.
A collection of 45 Proteus penneri strains was characterized with respect to their hemolytic activity and representative cell-free or only cell-bound hemolysin possessing strains were chosen for further study. Extracellular Proteus penneri hemolysin, which was investigated earlier by hybridization, reacted with monospecific antiserum against alpha-hemolysin of Escherichia coli. In this paper we also show, using the colony hybridization technique, that the alpha-hemolysin-like determinant is widely distributed among Proteus penneri strains. Because one of the strains tested, which expressed a high activity of cell-bound hemolytic factor, did not carry such a Hly determinant, the presence of a second hemolysin is postulated. We cannot demonstrate any difference in hybridization patterns of alpha- and beta-hemolytic Proteus penneri strains and accumulation of the toxin molecule inside the cells was also not observed. The existence of another control mechanism, external to the hly operon, for hemolysin gene is suggested.


Interface pressure measurement during surgery: a comparison of four operating table surfaces.
To compare the pressure-reducing and pressure-redistributing characteristics of four operating room (OR) table mattresses using interface pressure measurements, in two positions adopted for surgical procedures. Support surfaces were randomly assigned to 80 patients. These were: an overlay pad filled with fibres (the standard OR mattress), a custom-made viscoelastic polyurethane foam mattress, an inflatable mattress with air-filled cells and a fluid mattress. An XSENSOR full-body pressure-mapping pad was used to record interface pressures of 40 patients in the supine position and 40 patients in the lithotomy position. Measurements were analysed for peak pressure, peak pressure index, total contact surface area and the occurrence of a significant increase in interface pressure during the surgical procedure. The highest interface pressures were measured on the standard mattress, in both the supine and lithotomy position. Overall, the fluid mattress showed the best pressure-reducing and pressure-redistributing capacities. As long as no reference values are available for interface pressures under which no pressure-related damage will occur, clinical testing of OR table surfaces is still necessary.


Evidence of Chikungunya virus seroprevalence in Myanmar among dengue-suspected patients and healthy volunteers in 2013, 2015, and 2018.
Chikungunya virus (CHIKV) is a mosquito-borne virus known to cause acute febrile illness associated with debilitating polyarthritis. In 2019, several institutions in Myanmar reported a CHIKV outbreak. There are no official reports of CHIKV cases between 2011 and 2018. Therefore, this study sought to determine the seroprevalence of CHIKV infection before the 2019 outbreak. A total of 1,544 serum samples were collected from healthy volunteers and patients with febrile illnesses in Yangon, Mandalay, and the Myeik district in 2013, 2015, and 2018. Participants ranged from one month to 65 years of age. Antibody screening was performed with in-house anti-CHIKV IgG and IgM ELISA. A neutralization assay was used as a confirmatory test. The seroprevalence of anti-CHIKV IgM and anti-CHIKV IgG was 8.9% and 28.6%, respectively, with an overall seropositivity rate of 34.5%. A focus reduction neutralization assay confirmed 32.5% seroprevalence of CHIKV in the study population. Age, health status, and region were significantly associated with neutralizing antibodies (NAbs) and CHIKV seropositivity (p < 0.05), while gender was not (p = 0.9). Seroprevalence in 2013, 2015, and 2018 was 32.1%, 28.8%, and 37.3%, respectively. Of the clinical symptoms observed in participants with fevers, arthralgia was mainly noted in CHIKV-seropositive patients. The findings in this study reveal the circulation of CHIKV in Myanmar's Mandalay, Yangon, and Myeik regions before the 2019 CHIKV outbreak. As no treatment or vaccine for CHIKV exists, the virus must be monitored through systematic surveillance in Myanmar.


Telomeric repeats (TTAGGC)n are sufficient for chromosome capping function in Caenorhabditis elegans.
Telomeres are specialized structures located at the ends of linear eukaryotic chromosomes that ensure their complete replication and protect them from fusion and degradation. We report here the characterization of the telomeres of the nematode Caenorhabditis elegans. We show that the chromosomes terminate in 4-9 kb of tandem repeats of the sequence TTAGGC. Furthermore, we have isolated clones corresponding to 11 of the 12 C. elegans telomeres. Their subtelomeric sequences are all different from each other, demonstrating that the terminal TTAGGC repeats are sufficient for general chromosomal capping functions. Finally, we demonstrate that the me8 meiotic mutant, which is defective in X chromosome crossing over and segregation, bears a terminal deficiency, that was healed by the addition of telomeric repeats, presumably by the activity of a telomerase enzyme. The 11 cloned telomeres represent an important advance for the completion of the physical map and for the determination of the entire sequence of the C. elegans genome.


Dependence on the socio-economic system impairs the sustainability of pasture-based animal agriculture.
Livestock systems contribution to environmental change is controversial. Pasture-based systems are considered a sustainable alternative due to their adaptation to the use of local natural resources. However, they have limited productivity per product unit and, in Europe, depend on public economic support. Furthermore, they are heterogeneous in farm structure and resources use, which may determine their sustainability. We use emergy accounting to assess the sustainability of mountain pasture-based cattle systems and analyse the variability among farms. Emergy accounting assesses the sustainability performance of complex systems (i.e., farming systems) and their interaction with other systems (i.e., the environment and the socio-economic system) focusing on the origin, quality and quantity of the energy required for the system to function. Results show that pasture-based systems largely use local natural renewable resources but depend largely on the wider socio-economic system given their reliance on public economic support and purchased animal feeds. This economic dependence turns out in most farms largely using non-renewable resources. Increasing self-produced feeds and grazing on natural pastures can reduce the dependence on the socio-economic system and improve farm sustainability.


[Study on treatment of retinitis pigmentosa with traditional Chinese medicine by Flicker electroretinogram].
Study on treatment of 54 patients (106 eyes) of retinitis pigmentosa (RP) with traditional Chinese medicine was conducted by using modified method of electroretinography. Results showed: (1) Flicker response of electroretinogram was the most sensitive-criterion in examination, it was more effective when combined with infrared spectrogram. (2) The 30 Hz flicker index, response time were improved after TCM therapy in different hereditary types of RP, the improvement was significant in patients with Yang-Deficiency of Spleen-Kidney Syndrome and those of autosomal dominant inheritance type (P < 0.01). (3) Decrease of phase angle (phi) under different frequency of flicker after treatment was also significant statistically. The results suggested that flicker responses, which represents mainly retinal cone activity of patients, could be improved to a certain extent by TCM treatment, even in those with advanced retinal degeneration. TCM treatment could also enhance the bioactivity of nerve network and therefore have a definite significance in retarding the progression of disease and keeping the central vision. The flicker ERG, especially its flicker index, is an effective, sensitive and useful parameter for detection of visual function in patient with retinitis pigmentosa.


Gallbladder volvulus: a case report. Could the ultrasound be the key of the early diagnosis?
Gallbladder volvulus is a rare disease which may affect the elderly. It mimics clinically an acute cholecystitis, but the ultrasound signs may provide an early diagnosis: a very large, anteriorly floating gallbladder, with very thickened, multi layered wall, could orientate the physician to this rare disease. We present one case of gallbladder volvulus with its radiological signs. The symptoms, the etiology and the radiological examinations are discussed.


Systems Biology and Experimental Model Systems of Cancer.
Over the past decade, we have witnessed an increasing number of large-scale studies that have provided multi-omics data by high-throughput sequencing approaches. This has particularly helped with identifying key (epi)genetic alterations in cancers. Importantly, aberrations that lead to the activation of signaling networks through the disruption of normal cellular homeostasis is seen both in cancer cells and also in the neighboring tumor microenvironment. Cancer systems biology approaches have enabled the efficient integration of experimental data with computational algorithms and the implementation of actionable targeted therapies, as the exceptions, for the treatment of cancer. Comprehensive multi-omics data obtained through the sequencing of tumor samples and experimental model systems will be important in implementing novel cancer systems biology approaches and increasing their efficacy for tailoring novel personalized treatment modalities in cancer. In this review, we discuss emerging cancer systems biology approaches based on multi-omics data derived from bulk and single-cell genomics studies in addition to existing experimental model systems that play a critical role in understanding (epi)genetic heterogeneity and therapy resistance in cancer.


Intra-articular hyaluronic acid preparations for use in the treatment of osteoarthritis.
Intra-articular hyaluronic acid preparations have been available for the treatment of osteoarthritis of the knee for over 15 years. Their use has been limited by cost, difficulties of administration and conflicting evidence of efficacy. Difficulties in conducting adequate clinical trials have resulted in the appearance of multiple meta-analyses whose findings are not congruent. The appearance of a single injection agent and a better understanding of the mechanisms by which this intervention is effective may help to solve this ongoing problem in healthcare research.


Tumor-targeting of viral vectors for cancer gene therapy by using antibodies or their genes against tumor-associated antigens.
Gene therapy is a promising modality for the treatment of malignant tumors for which conventional therapies are often inadequate. Various therapeutic genes have shown promise for tumor cell killing. However, successful gene therapy depends on the development of efficient and targeted gene transfer vectors. The aim of this review is to summarize the tumor-targeting viral vectors for cancer gene therapy by utilizing antibodies or genes against tumor-associated antigens.


Scaling prediction errors to reward variability benefits error-driven learning in humans.
Effective error-driven learning requires individuals to adapt learning to environmental reward variability. The adaptive mechanism may involve decays in learning rate across subsequent trials, as shown previously, and rescaling of reward prediction errors. The present study investigated the influence of prediction error scaling and, in particular, the consequences for learning performance. Participants explicitly predicted reward magnitudes that were drawn from different probability distributions with specific standard deviations. By fitting the data with reinforcement learning models, we found scaling of prediction errors, in addition to the learning rate decay shown previously. Importantly, the prediction error scaling was closely related to learning performance, defined as accuracy in predicting the mean of reward distributions, across individual participants. In addition, participants who scaled prediction errors relative to standard deviation also presented with more similar performance for different standard deviations, indicating that increases in standard deviation did not substantially decrease "adapters'" accuracy in predicting the means of reward distributions. However, exaggerated scaling beyond the standard deviation resulted in impaired performance. Thus efficient adaptation makes learning more robust to changing variability.


Proton transport and phosphorylation of tonoplast polypeptides from zucchini are stimulated by the phospholipid platelet-activating factor.
The ether phospholipid platelet-activating factor and certain similar phospholipids, including lysophosphatidylcholine, are known to stimulate both H(+) transport and protein phosphorylation in plant microsomal membranes. In the present work, several polypeptides in highly purified tonoplast membranes from zucchini (Cucurbita pepo L.) showed platelet-activating factor-dependent phosphorylation. Comparison of protein phosphorylation in different membrane fractions separated by sucrose step density gradient centrifugation indicated that some of the phosphoproteins were contaminants or were common to several membrane fractions, but platelet-activating factor-dependent phosphorylation of peptides at 30, 53, and perhaps 100 kilodaltons was tonoplast specific. The phosphoprotein of 53 kilodaltons was shown by three different approaches (one- and two-dimensional polyacrylamide gel electrophoresis, western blots, and immunoprecipitation) to cross-react with antibody raised against the B subunit of the tonoplast ATPase from red beet (Beta vulgaris L.).


Rehabilitation in a patient with replantation of amputated distal leg.
Many studies have been reported on replantation of an upper extremity after traumatic amputation, but there are only a few case reports on replantation of the lower extremities rather than amputation surgery. This is due to preoperative factors, complications and the possibility of good prosthetic substitution.We describe here the dynamic evaluation necessary for a continuous rehabilitation treatment in a subject with replanted left foot after traumatic amputation. A 58-year-old male person with amputation of the left leg at the level of the left talocrural joint, with talar dome and bimalleolar fractures and complete section of the blood vessels, nerves and tendons was considered for replantation surgery 7 hours after a traumatic injury.For an accurate evaluation of the postoperative conditions over time, clinical functional assessment combined with imaging and neurophysiological examination were conducted.Rehabilitation program is aimed to train the motor and sensory function of the replanted foot and to prevent undesired biomechanical changes that limit person's ability to perform everyday tasks. During the rehabilitation program there were a progressive recovery of the patient's protective sensation, active motion angles of the left ankle joint and muscle power of the replanted leg. Those are sufficient for walking activity and help the patient considerably in performing his everyday minimal housework. A well designed postoperative dynamic rehabilitation program is necessary in order to regain functionality after successful distal leg replantation surgery. The clinical and imaging evaluation support a dynamic rehabilitation program adapted to different stages of functional recovery.


Comparison of semilunar coronally repositioned flap with gingival massaging using an Ayurvedic product (irimedadi taila) in the treatment of class-I gingival recession: A clinical study.
To study the comparison in terms of root coverage the effect of gingival massaging using an ayurvedic product and semilunar coronally repositioned flap (SCRF) to assess the treatment outcomes in the management of Miller's class I gingival recessions over a-6 mo period. The present study comprised of total of 90 sites of Miller's class-I gingival recessions in the maxillary anteriors, the sites were divided into three groups each comprising 30 sites, Group I-were treated by massaging using a Placebo (Ghee) Group II-were treated by massaging using an ayurvedic product (irimedadi taila). Group III-were treated by SCRF. Clinical parameters assessed included recession height, recession width, probing pocket depth, width of attached gingiva, clinical attachment level and thickness of keratinized tissue. Clinical recordings were performed at baseline and 6 mo later. The results were analyzed to determine improvements in the clinical parameters. The comparison was done using Wilcoxon signed rank test. The overall differences in the clinical improvements between the three groups was done using Kruskal-Wallis test. The probability value (P-value) of less than 0.01 was considered as statistically significant. Non-surgical periodontal therapy and gingival massaging improves facial gingival recessions and prevents further progression of mucogingival defects. Root coverage was achieved in both the experimental groups. The SCRF group proved to be superior in terms of all the clinical parameters. Root coverage is significantly better with semilunar coronally repositioned flap compared with the gingival massaging technique in the treatment of shallow maxillary Miller class I gingival recession defects.


Life and evolution in computers.
This paper argues for the possibility of 'artificial life' and computational evolution, first by discussing (via a highly simplified version) John von Neumann's self-reproducing automation and then by presenting some recent work focusing on computational evolution, in which 'cellular automata', a form of parallel and decentralized computing system, are evolved via 'genetic algorithms'. It is argued that such in silico experiments can help to make sense of the question of whether we can eventually build computers that are intelligent and alive.


Involvement of protein kinase A and C in norepinephrine- and angiotensin II-induced modulation of cardiac IKs.
The slow component of the delayed rectifier K(+) current (IKs) is one of the major repolarizing currents in the heart. Yet, the signaling mechanisms for norepinephrine- and angiotensin II-induced modulation of IKs in cardiac myocytes are far from being well understood. The whole-cell patch clamp technique was used to study the effects of norepinephrine and angiotensin II on IKs in guinea pig cardiac myocytes. Both the α1- and β-adrenoceptor inhibitors attenuated norepinephrine-induced enhancement of IKs, which was also significantly depressed by inhibitors of protein kinase A and C. Angiotensin II-induced inhibition of the IKs was inhibited by angiotensin type 1 receptor blocker losartan and protein kinase C inhibitor. Norepinephrine and angiotensin II modulated IKs with opposite effects and distinct mechanisms. The activation of protein kinase A was the major component of the norepinephrine-induced activation of IKs while the activation of protein kinase C was responsible for the angiotensin II-induced inhibition of IKs. There was crosstalk between the α1- and β-adrenoceptor that also contributed to the norepinephrine-induced enhancement of IKs. This current study provides new insight into the cellular signaling mechanisms of norepinephrine and angiotensin II, the two important modulators of cardiovascular function.


Primary biliary cirrhosis-specific antimitochondrial antibodies in neonatal haemochromatosis.
Neonatal hemochromatosis (NH) is characterised by severe liver injury and extrahepatic siderosis sparing the reticuloendothelial system. Its aetiology is obscure, although it has been proposed as an alloimmune disease, resulting from immunological reaction to self-antigens (alloantigens) which the body recognizes as foreign. We studied an infant with NH and his mother whose sera contained antimitochondrial antibody (AMA), the hallmark of primary biliary cirrhosis (PBC). To investigate the origin of AMA in the infant, we studied isotype distributions in serum from the mother and infant. Serum samples were obtained at diagnosis of NH, after liver transplantation (LT; age 1 month), and over the ensuing 17 months. At NH diagnosis, infant and maternal serum contained AMA of the IgG isotype, predominantly of the G3 and G1 subclasses. AMA strongly reacted against the pyruvate dehydrogenase complex E2 subunit (PDC-E2), the major PBC-specific AMA autoantigen. Anti-PDC-E2 responses in both infant and mother declined over time, being present 2 months after LT (mother and child) and absent 10 months later (mother) and 17 months later (child). The association of maternally transferred IgG1 and IgG3 subclass AMA with the appearance of liver damage in an infant with NH may suggest a causal link between antibody and liver damage.


Comparative evaluation of genetic assays to identify oral pre-cancerous fields.
Oral squamous cell carcinomas often develop in a pre-cancerous field, defined as mucosal epithelium with cancer-related genetic alterations, and which may appear as a clinically visible lesion. The test characteristics of three genetic assays that were developed to detect pre-cancerous fields were investigated and compared to histology. In total, 10 pre-cancerous fields that were not visible at clinical inspection and gave rise to malignant transformation based on an identical TP53 mutation in tumor and mucosal epithelium in the surgical margin, as well as 10 normal oral mucosa specimens were analyzed for numerical chromosomal changes with multiplex ligation-dependent probe amplification (MLPA), for loss of heterozygosity (LOH), with microsatellite PCR and for DNA index alterations with DNA image analysis. No alterations were detected in normal tissue by either of the assays. Both MLPA and LOH assays detected all pre-cancerous fields. DNA cytometry identified aneuploidy in four of 10 pre-cancerous fields, while the corresponding tumors that developed in these fields were shown to be aneuploid. Both the MLPA and LOH assay seem suitable for screening pre-cancerous fields in subjects at high risk for oral cancer even in the absence of clinically abnormal appearing oral mucosa. Measurements of DNA index might be valuable to determine the time to progression.


[Twins in cultural and psychic life. African examples].
In Africa, twin births were and are still considered to be events of extraordinary importance. Traditional beliefs give to twins a special position as sacred monsters and devote to them a variety of ritual celebrations. The different versions of the dogon myth of the creation of the world tell the symbolic events that led to separation of Heaven and Earth, of gods and first men on earth, of female and men of religious leaders and other inhabitants. The dual faces of androgynous twins provide a paradigm for a long process of differentiation culminating in definitive separation when turned into animals occupying opposing territories. Ibeji statuettes are a central element in a twin-related cult practiced by the Yoruba people. The birth or death of twins is considered as a potential threat for future children. For this reason, the Yorubas treat these statuettes as if they were alive. The anxiety neurosis of Josephine, a modern African woman, expressed itself through a recurrent dream. Psychotherapy allowed her to understand the meaning of these dream images.


Carbon isotope effects of DDTs in carrot during the digestion process using an in vitro test.
Compound-specific carbon isotope ratio analysis is a promising tool to assess the origins and fates of organic contaminants in many fields. The present study aims to investigate the isotope effects of dichloro-diphenyl-trichloroethane (DDT) and its degradates in carrots during digestion processes simulating the human gastrointestinal tract. To accurately interpret isotopic data obtained for unreleased DDTs (p,p-DDT, p,p-DDD and p,p-DDE) from carrots during digestion, spiked carrots with known delta(13)C values of DDTs were incubated in simulated gastric and intestinal solutions using a static in vitro model of the human gut. The delta(13)C values and concentrations of DDTs remaining in the carrot and in the digestive solutions were measured. The difference in the delta(13)C values of the added DDTs and the matrix-bound DDTs after digestion was always <0.50 per thousand, which is within the technical specification of the analytical system, although the released DDTs increased or decreased under the digestion conditions. The study demonstrated that there were no significant carbon isotopic fractionations during digestion. To our knowledge, this is the first report demonstrating the isotope effect of organic compounds during stomach and small intestine digestion, and the first reported isotope analyses of DDTs.


Oxygen therapy limiting peripheral oxygen saturation to 89-93% is associated with a better survival prognosis for critically ill COVID-19 patients at high altitudes.
Patients admitted to the Intensive Care Unit (ICU) with acute hypoxemic respiratory failure automatically receive oxygen therapy to improve inspiratory oxygen fraction (FiO2). Supplemental oxygen is the most prescribed drug for critically ill patients regardless of altitude of residence. In high altitude dwellers (i.e. in La Paz [≈3,400 m] and El Alto [≈4,150 m] in Bolivia), a peripheral oxygen saturation (SatpO2) of 89-95% and an arterial partial pressure of oxygen (PaO2) of 50-67 mmHg (lower as altitude rises), are considered normal values for arterial blood. Consequently, it has been suggested that limiting oxygen therapy to maintain SatpO2 around normoxia may help avoid episodes of hypoxemia, hyperoxemia, intermittent hypoxemia, and ultimately, mortality. In this study, we evaluated the impact of oxygen therapy on the mortality of critically ill COVID-19 patients who permanently live at high altitudes. A multicenter cross-sectional descriptive observational study was performed on 100 patients admitted to the ICU at the "Clinica Los Andes" (in La Paz city) and "Agramont" and "Del Norte" Hospitals (in El Alto city). Our results show that: 1) as expected, fatal cases were detected only in patients who required intubation and connection to invasive mechanical ventilation as a last resort to overcome their life-threatening desaturation; 2) among intubated patients, prolonged periods in normoxia are associated with survival, prolonged periods in hypoxemia are associated with death, and time spent in hyperoxemia shows no association with survival or mortality; 3) the oxygenation limits required to effectively support the intubated patients' survival in the ICU are between 89% and 93%; 4) among intubated patients with similar periods of normoxemic oxygenation, those with better SOFA scores survive; and 5) a lower frequency of observable reoxygenation events is not associated with survival. In conclusion, our findings indicate that high-altitude patients entering an ICU at altitudes of 3,400 - 4,150 m should undergo oxygen therapy to maintain oxygenation levels between 89 and 93 %.


[Effects of polyacrylamide on settling and separation of oil droplets in polymer flooding produced water].
The research found anion polyacrylamide (HPAM) had positive and negative effects on oil-water separation. Polymer made oily wastewater's viscosity increase and reduce rising velocity, and polymer can also increase intensity of water films between oil droplets and lengthen coalescence time of oil droplets. Those were not in favor of settling and separation for oil droplets. The positive effects on separation were that polyacrylamide had flocculating activity and made small droplets contact each other and combine into big droplets. When polymer's molecular weight was 2.72 x 10(6), and concentration was less than 800 mg/L, polymer was in favor of oil droplets settling and separation. The prime reason for oily wastewater of polymer flooding difficult to dispose was that initial median diameters of oil droplets were small. The transverse flow oil separator can intensify oil droplets combination and shorten rising time. The locale experiments showed the separator was suitable for dealing with oily wastewater of polymer flooding.


Resistance training in the treatment of non-insulin-dependent diabetes mellitus.
Aerobic endurance exercise has traditionally been advocated in the treatment of non-insulin-dependent diabetes mellitus (NIDDM). However, the effect of aerobic endurance exercise programs on long-term glycaemic control is small to moderate. The aim of the present study was to determine the effect of circuit resistance training on long-term glycaemic control (HbA1c) and to examine the potential association between muscle size and glycaemic control in NIDDM subjects. Eight NIDDM subjects participated in a 3 month individualized progressive resistance training program (moderate intensity, high-volume) twice a week with measurements of HbA1c, lipids, blood pressure, VO2max and thigh muscle cross-sectional area. There was a significant improvement in HbA1c (8.8% - 8.2%; p < 0.05). Muscle endurance increased by 32 +/- 23% (p < 0.05), and the cross-sectional area of m. vastus lateralis increased by 21% (p < 0.001). There was a strong inverse correlation between HbA1c and muscle cross-sectional area (knee extensors) after the exercise period (r = -0.73; p < 0.05). Circuit resistance training seems to be feasible in moderately obese, sedentary elderly NIDDM subjects and the inclusion of circuit resistance training in exercise training programs for NIDDM subjects should be considered.


Carcinoid Syndrome-Induced Ventricular Tachycardia.
Introduction. Carcinoid tumors are rare neuroendocrine malignancies that secrete multiple bioactive substances. These bioactive substances are responsible for the carcinoid syndrome characterized by diarrhea, flushing, syncope, and right-sided valvular heart disease. Previous case reports have described carcinoid syndrome associated with coronary vasospasm and the well-characterized carcinoid heart disease. Case. Our patient is a 73-year-old female with complex past medical history most notable for metastatic carcinoid tumors diagnosed in 2013-05. She initially presented in 2014-09 with syncope and dizziness associated with sinus pause on an event monitor. She received a pacemaker given normal left ventricular function and was discharged. However, she was readmitted with similar symptoms corresponding to multiple episodes of ventricular tachycardia. She was started on high-dose beta blockade and has had no recurrence of arrhythmia over a follow-up period of 12 months. Conclusion. We hypothesize that the patient's ventricular tachycardia was mediated by the multiple bioactive substances secreted by her carcinoid tumors. Her carcinoid tumor biomarkers were elevated and other explanations for arrhythmia were investigated and ruled out. To our knowledge, this is the first case of ventricular tachycardia mediated by carcinoid syndrome and suppressed by beta-blocker. Further investigation into this relationship is needed.


An In Situ One-Pot Synthetic Approach towards Multivariate Zirconium MOFs.
Chemically highly stable MOFs incorporating multiple functionalities are of great interest for applications under harsh environments. Herein, we presented a facile one-pot synthetic strategy to incorporate multiple functionalities into stable Zr-MOFs from mixed ligands of different geometry and connectivity. Via our strategy, tetratopic tetrakis(4-carboxyphenyl)porphyrin (TCPP) ligands were successfully integrated into UiO-66 while maintaining the crystal structure, morphology, and ultrahigh chemical stability of UiO-66. The amount of incorporated TCPP is controllable. Through various combinations of BDC derivatives and TCPP, 49 MOFs with multiple functionalities were obtained. Among them, MOFs modified with FeTCPPCl were demonstrated to be catalytically active for the oxidation of ABTS. We anticipate our strategy to provide a facile route to introduce multiple functionalities into stable Zr-MOFs for a wide variety of potential applications.


How prevalent and costly are Choosing Wisely low-value services? Evidence from Medicare beneficiaries.
(1) Through the Choosing Wisely initiative, medical specialty societies identified non-indicated cardiac testing in low-risk patients and short-interval dual-energy X-ray absorptiometry (DXA) or bone density testing as low-value care. (2) Nationally, 13 percent of low-risk Medicare beneficiaries received non-indicated cardiac tests, and 10 percent of DXAs reimbursed by Medicare were administered at inappropriately short intervals. There is significant geographic variation in the provision of these services. (2) Carefully designed policy and payment changes will likely prove most effective in reducing low-value care.


Graphene coated ZnO nanowire optical waveguides.
We report the fabrication and characterization of freestanding graphene coated ZnO nanowires (GZNs) for optical waveguiding. The GZNs are fabricated using a tape-assist transfer under micromanipulation. Owing to the deep-subwavelength diameter and high index contrast of the ZnO nanowire waveguide, light-graphene interaction is significantly enhanced by the strong surface optical fields, resulting in a linear absorption as high as 0.11 dB/µm in a 606-nm-diameter GZN at 1550-nm wavelength. Launched by 1550-nm-wavelength femto-second pulses, a 475-nm-diameter GZN with a graphene coating length of merely 24 µm exhibits evident nonlinear saturable absorption with a peak power threshold down to 1.3 W. In addition, we also demonstrate a transmission modulation for 1550-nm-wavelength signal with a 590-nm-diameter GZN, showing the possibility of using GZN waveguides as nanoscale bulding blocks for nanophotonic devices.


Efficacy of intrathecal bupivacaine: how important is the flow rate?
We present two cases of cancer patients with intractable mechanical and visceral pain that was unrelieved with either comprehensive medical management or intrathecal morphine who received intrathecal bupivacaine. While the continuous administration of a seemingly significant daily dose neither relieved pain nor caused measurable clinical changes, the addition of small, presumably negligible bolus doses on top of the continuous infusion resulted in spectacular pain control, clear thermoanalgesic suspended block, and in one of the patients, significant hypotension. To the best of our knowledge, such an observation has neither been reported before nor can we provide a satisfactory explanation for it. However, we believe it may have significant implications for the treatment of some patients, in particular, cancer patients with mechanical pain that cannot be adequately relieved with morphine whatever the route of administration.


The effects of Tai Chi on waist circumference and blood pressure in the elderly.
[Purpose] The purpose of this study was to investigate the effects of Tai Chi on waist circumference and blood pressure in the elderly. The present study used a nonequivalent control group pretest-posttest design. [Subjects and Methods] Sixty-eight elderly individuals residing in J city were divided into 2 groups: 34 in the experimental group, who received Tai Chi training for 6 weeks, and 34 in the control group, who did not receive Tai Chi training. Simplified Yang style 24-form Tai Chi was used as the intervention, which was conducted for 60 minutes per session, 5 sessions per week, for a total of 6 weeks. In each session, subjects in the experimental group conducted 10 minutes of warm-up exercises, 45 minutes of Tai Chi, and 5 minutes of cool-down exercises. Waist circumference and blood pressure were measured before and after the 6-week intervention. [Results] Waist circumference and blood pressure decreased significantly after the 6-week intervention in the experimental group compared with the control group. [Conclusion] Tai Chi can be used as an effective intervention to improve waist circumference and blood pressure in the elderly.


Lymphotoxin and an associated 33-kDa glycoprotein are expressed on the surface of an activated human T cell hybridoma.
A human T cell hybridoma, II-23.D7, was induced with phorbol ester to express a surface form of lymphotoxin (LT, TNF-beta) and an associated 33-kDa glycoprotein. The LT epitopes were detected by surface immunofluorescence staining and by immunoprecipitation from radioiodinated or biosynthetically labeled cells with the use of anti-rLT polyclonal and monoclonal antibodies. The epitopes detected by the antibody were related to LT because adsorption of the anti-rLT with PMA-activated II-23.D7 cells resulted in the removal of the neutralizing titer of the anti-rLT antiserum. Immunoprecipitation of surface radioiodinated II-23.D7 cells revealed two bands of 25 kDa and 33 kDa that were specifically precipitated with anti-rLT, but not anti-rTNF antibodies. Enzymatic digestion with glycanases showed both proteins to have N-linked carbohydrate, with O-linked sugar limited to the 25-kDa protein. To determine the biochemical relationship between these proteins, the two LT-like forms were purified from detergent-solubilized II-23.D7 cells by immunoaffinity chromatography. Peptide mapping using CNBr cleavage showed the 25-kDa surface form to be identical to rLT, whereas the 33-kDa protein was different. Biosynthetic labeling studies showed that p33 contained both methionine and cysteine, whereas the p25 contained only methionine. Thus, the surface LT form lacks a leader peptide indicating an anchoring mechanism distinct from that described for membrane TNF. The nature of the attachment of this LT form to the membrane surface is not clear, however, neither TNF receptor binding nor lipid linkages appear to be involved. The accessory protein, p33, may anchor LT to the surface. These findings identify a new characteristic of LT and point toward an additional pathway by which T lymphocytes may mediate cytolytic activity and regulate inflammatory processes.


A case of clear cell eccrine porocarcinoma.
Eccrine porocarcinoma (EP) is a rare malignant tumor arising from the intraepidermal eccrine duct. The tumor cells frequently contain glycogen, but prominent clear cell changes in EP are rarely reported. A 78-year-old woman presented with a slightly pruritic, erythematous, verrucous plaque on her left thigh. Histopathological examination revealed intraepidermal tumor cell nests composed of small basaloid cells and duct-like structures lined by periodic acid-Schiff (PAS)-positive cuticles. Besides the typical findings of EP, clear cell changes were predominantly observed in the tumor cell aggregations. Herein we report a case of the clear cell variant of EP rarely reported in previous literature.


Influence of Finishing and Polishing Techniques and Abrasion on Transmittance and Roughness of Composite Resins.
The aim of this study was to evaluate the influence of finishing and polishing systems and toothbrush abrasion on transmittance (T) and surface roughness (Ra) of three composite resins (Filtek Z350 XT, Tetric N-Ceram, and IPS Empress Direct). Eighteen resin disks (10 mm diameter × 2 mm thick) finished by polyester strips had initial surface smoothness recorded, representing phase 1 (P1). Specimens were divided into three groups (n=6) according to the finishing/polishing instrument used (OneGloss, TopGloss, and Sof-Lex) to compose phase 2 samples (P2). Then specimens were subjected to 514 cycles of toothbrush simulation using a toothpaste slurry, with a constant load applied to soft bristles, and were then washed (phase 3=P3). After each phase, the specimens were examined by an optical profiler and spectrophotometer to measure Ra and T. Data were analyzed by analysis of variance, Tukey and Pearson tests. T values were statistically influenced by composite resin ( p=0.000) and phase of measurement ( p=0.000) factors, while the finishing/polishing system used ( p=0.741) did not affect T. On the other hand, Ra values were statistically affected by the factor finishing/polishing system ( p=0.000), but not by composite resin ( p=0.100) and phase of measurement ( p=0.451). Tetric N-Ceram and Empress Direct presented higher values of roughness when polished by OneGloss, while TopGloss and Sof-Lex showed a lower roughness. It can be concluded that composite resins transmitted more light after dental abrasion. Transmittance of composite resins was not modified by the distinct roughness created by finishing/polishing instruments.


The El Tor biotype of Vibrio cholerae exhibits a growth advantage in the stationary phase in mixed cultures with the classical biotype.
Vibrio cholerae strains of the O1 serogroup that typically cause epidemic cholera can be classified into two biotypes, classical and El Tor. The El Tor biotype emerged in 1961 and subsequently displaced the classical biotype as a cause of cholera throughout the world. In this study we demonstrate that when strains of the El Tor and classical biotypes were cocultured in standard LB medium, the El Tor strains clearly had a competitive growth advantage over the classical biotype starting from the late stationary phase and could eventually take over the population. The classical biotype produces extracellular protease(s) in the stationary phase, and the amounts of amino acids and small peptides in the late stationary and death phase culture filtrates of the classical biotype were higher than those in the corresponding culture filtrates of the El Tor biotype. The El Tor biotype cells could utilize the amino acids more efficiently than the classical biotype under the alkaline pH of the stationary phase cultures but not in medium buffered to neutral pH. The growth advantage of the El Tor biotype was also observed in vivo using the ligated rabbit ileal loop and infant mouse animal models.


Physicochemical properties of fowlpox virus deoxyribonucleic acid and its anomalous infectious behavior.
Randall, Charles C. (University of Mississippi, Jackson), Lanelle G. Gafford, Richard L. Soehner, and James M. Hyde. Physicochemical properties of fowlpox virus deoxyribonucleic acid and its anomalous infectious behavior. J. Bacteriol. 91:95-100. 1966.-Deoxyribonucleic acid (DNA) was extracted from fowlpox virus-infected tissue, purified inclusions, and purified virus by five variations of detergent and phenol methods. Phenol methods gave a poor yield, whereas detergent techniques extracted up to 78% of the DNA. The buoyant density was 1.695 g/ml, and the melting temperature in 7.2 m NaClO(4) was 39 C, both approximately equivalent to a guanine plus cytosine content of 35 moles per cent. Further proof of the double-stranded nature of the DNA was shown by the characteristic behavior toward deoxyribonuclease, formaldehyde, and heat. Infectious DNA was obtained by the various methods described, but this manifestation of biological activity was capricious and for unknown reasons was often not evident. The infectivity could not be related quantitatively to the amount of DNA employed. Furthermore, the infectious nature of fowlpox virus DNA was demonstrable only when the route of infection was the chorioallantoic membrane. In contrast, whole virus infected both membrane and chick skin with equal efficiency.


Pharmacokinetics of morphine and its surrogates. XI: Effect of simultaneously administered naltrexone and morphine on the pharmacokinetics and pharmacodynamics of each in the dog.
There were no dramatic modifications of the pharmacokinetics in the dog of i.v. bolus doses of 0.5, 2.7 and 5 mg kg-1 morphine by coadministering i.v. 5 mg kg-1 naltrexone as bolus injections over 15-20s and 12.3 mg kg-1 by continuous infusion. Morphine's terminal half-life, clearances, apparent volumes of distribution (except for that of the central compartment), percentages of drug and conjugated metabolite excreted in urine and bile did not differ significantly by paired t-test (probability (p) greater than 0.05 for rejection of the null hypothesis of no difference) when naltrexone was coadministered. There were no statistically significant (by t-test) modifications of the plasma pharmacokinetics in the dog of i.v. bolus doses of 5 mg kg-1 naltrexone with and without morphine coadministration except for the coefficient of the second (or terminal) exponential of the sum that fitted the plasma concentration-time data of naltrexone. Although morphine coadministration did not significantly affect the terminal half-life of naltrexone, its clearances or apparent volumes of distribution by t-test of the differences between averages (with each dog equally weighted), drug coadministration did significantly (by t-test) affect the fraction of naltrexone dose secreted into bile as conjugate (fB), the fraction of the dose excreted as conjugate in urine, and the fraction excreted elsewhere (f'B). Although naltrexone reversed the central action of morphine in affecting monitored pupil diameters, it did not antagonize the peripheral effects of morphine in perturbing renal and biliary flow rates. This led to a larger fraction of the naltrexone dose being metabolized to conjugate on morphine coadministration. Since less naltrexone conjugate was renally and biliary excreted initially, due to morphine inhibition of the initial renal and biliary processes, naltrexone conjugate plasma concentrations were higher when morphine was coadministered.


Detection of the diuretic hydrochlorothiazide in a doping control urine sample as the result of a non-steroidal anti-inflammatory drug (NSAID) tablet contamination.
Hydrochlorothiazide (HCTZ, 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide-1,1-dioxide) belongs to the class of diuretic agents that represent one of today's cornerstones of the treatment of hypertensive patients. In addition to its clinical relevance, HCTZ is prohibited in sports according to the regulations of the World Anti-Doping Agency (WADA) at all times and has frequently been detected in sports drug testing urine samples worldwide since its ban was introduced in 1988. Despite these facts, the adverse analytical finding concerning HCTZ in an in-competition routine doping control sample collected in December 2014 was further investigated, particularly motivated by the comparably low urinary concentration of the drug accounting for approximately 5ng/mL. The athlete in question did not declare the use of any nutritional supplement or medication other than the ingestion of a non-steroidal anti-inflammatory drug (NSAID) prior to competition. Hence, the drug (formulated as coated tablet) provided by the athlete as well as the corresponding retention sample of the manufacturer were analyzed. Noteworthy, both samples confirmed the presence of about 2μg of HCTZ per tablet. In order to further probe for the plausibility of the observed urinary HCTZ concentrations with the scenario of drug ingestion and subsequent doping control sample collection, administration studies with produced HCTZ-spiked placebo-tablets (2.5μg of HCTZ/tablet) were conducted. Urine specimens were collected prior to and after ingestion of the drug and subjected to routine doping control analytical procedures employing liquid chromatography/tandem mass spectrometry. While blank urine samples returned negative test results, post-administration specimens were found to contain HCTZ at concentrations of approximately 1-16ng/mL, which supported the athlete's inadvertent intake of HCTZ via contaminated NSAID tablets. Due to the substantial sensitivity of test methods employed today by doping control laboratories, even drug contaminations ranging within the good manufacturing practice (GMP) limit of 10ppm overall carry-over can evidently lead to adverse analytical findings. This calls into question whether selected (classes of) substances such as diuretics should be reported only when exceeding a defined reporting level and/or whether adverse analytical findings of non-threshold substances should be reported with an estimated semi-quantitative concentration of the identified substance to facilitate the result management by anti-doping organizations.


In a mouse model relevant for post-traumatic stress disorder, selective brain steroidogenic stimulants (SBSS) improve behavioral deficits by normalizing allopregnanolone biosynthesis.
The pathophysiological role of the neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone) in neuropsychiatric disorders has been highlighted in several recent investigations. For instance, allopregnanolone levels are decreased in the CSF of patients with post-traumatic stress disorder (PTSD) and major unipolar depression. Neurosteroidogenic antidepressants, including fluoxetine and analogs, correct this decrease in a manner that correlates with improved depressive symptoms. PTSD-like behavioral dysfunctions, including heightened aggression, exaggerated fear, and anxiety-like behavior associated with a decrease in corticolimbic allopregnanolone content are modeled in mice by protracted social isolation stress. Allopregnanolone is not only synthesized by principal glutamatergic and gamma-aminobutyric acid (GABA)ergic neurons, but also locally, potently, positively, and allosterically modulates GABA action at postsynaptic and extrasynaptic GABAA receptors. Hence, this paper will review preclinical studies, which show that in socially isolated mice, rather than selective serotonin reuptake inhibitor mechanisms, allopregnanolone biosynthesis in glutamatergic corticolimbic neurons offers a nontraditional target for fluoxetine to decrease signs of aggression, normalize fear responses, and decrease anxiety-like behavior. At low selective serotonin reuptake inhibitor-inactive doses, fluoxetine and related congeners potently increase allopregnanolone levels by acting as potent selective brain steroidogenic stimulants (SBSS), thereby facilitating GABAA receptor neurotransmission and improving behavioral dysfunctions. Although the precise molecular mechanisms that underlie the action of these drugs are not fully understood, findings from socially isolated mice may ultimately generate insights into novel drug targets for the treatment of psychiatric disorders, such as anxiety and panic disorders, depression, and PTSD.


Increased levels of PPARbeta/delta and cyclin D1 in flat dysplastic ACF and adenomas in Apc(Min/+) mice.
In Apc(Min/+) (Min; multiple intestinal neoplasia) mice two separate populations of aberrant crypt foci (ACF) develop in the colon after azoxymethane (AOM) exposure. ACF(Min), with a flat appearance, severe dysplasia and increased beta-catenin expression, are related to adenoma development, whereas classic ACF, with elevated structure, hyperplasia and normal beta-catenin level, are probably not. The expressions of peroxisome proliferator-activated receptors (PPARs) beta/delta, cyclin D1 and beta-catenin in ACF, adenoma and normal tissue from AOM-treated Apc(Min/+) mice and a familial adenomatous polyposis (FAP) patient colon tumour were assessed by immunohistochemistry and immunoblotting. The flat ACF (ACF(Min)) displayed increased cytoplasmic levels of beta-catenin, and increased levels of cyclin D1 and PPARbeta/delta. In contrast, the expression in classic ACF resembled normal mucosa. Adenomas from Apc(Min/+) mice, as well as a FAP patient colon tumour, displayed increased nuclear and cytoplasmic levels of beta-catenin, and the same expression patterns of cyclin D1 and PPARbeta/delta as those found in flat ACF. In addition to activation of the Wnt signalling pathway in both flat ACF and in adenomas in Apc(Min/+) mice, the increased expression of PPARbeta/delta in these lesions could be a target for pro-inflammatory signals important for growth and reduced apoptosis.


Mechanism of vasorelaxation induced by Tridax procumbens extract in rat thoracic aorta.
Tridax procumbens (Linn) (Asteraceae) is one of the herbs widely distributed in many parts of the world. Its leaves have long been used for the treatment of hypertension in Nigeria. Previous studies have shown that aqueous leaves of T. procumbens extract (TPE) lowers blood pressure through endothelium-dependent and -independent mechanism in the aortic rings isolated from normotensive rats. The aim of the present study was to further investigate mechanisms of TPE-induced relaxation in the aortic artery by assessing its mechanistic interactions with nitric oxide (NO) synthase, cyclic guanosine monophosphate (cGMP), and cyclic adenosine monophosphate (cAMP). The aortic artery isolated from healthy, young adult normotensive Wistar albino rats (250-300 g) were pre-contracted with phenylephrine (PE) (10-7 M) and KCl (60 mM) and were treated with various concentrations of aqueous extract of TPE (0.5-9.0 mg/ml). The changes in arterial tension were recorded using Ugo Basile model 7004 coupled to data capsule acquisition system model 17400. The interaction between TPE with cAMP and cGMP inhibitors was also evaluated. The results showed that the TPE (0.5-9.0 mg/ml) significantly (P < 0.05) reduced the contraction induced by PE in a concentration-dependent manner. The vasorelaxant effect caused by the TPE was significantly (P < 0.05) attenuated with pre-incubation of cGMP (Rp-8Br PET cGMPS) and cAMP (Rp-AMP) inhibitor, respectively. These results suggest that TPE causes vasodilatory effects in a concentration-dependent manner in the isolated rat aortic artery. The mechanism of action of TPE is complex. A part of its relaxing effect is mediated directly by blocking or modulating cGMP and cAMP.


[HTLV-I infection in Spain. Analysis of 24 cases identified until November, 1994. Spanish Group for the Study of HTLV-I/II)].
HTLV-I is a human retrovirus which has been implicated in the genesis of tropical spastic paraparesia (TSP), adult T-cell leukemia (ATL) and some patients with uveitis, subacute arthropathies and lymphocytary alveolitis. The virus is endemic in some zones of the Caribbean countries, Japan, subsaharian Africa, Middle East and Melanesia. Given that HTLV-I is transmitted by similar routes as HIV, anti-HTLV-I antibody screening is carried out in blood donors in some countries. The clinical, epidemiologic and virologic characteristics of the patients with HTLV-I infection identified in Spain up to November 1994 are described. Twenty-four Spanish residents have been identified with HTLV-I infection including 16 Spaniards and 8 immigrants from endemic areas. Thirteen (53%) are males and 11 (47%) females. Most of the persons born in Spain (12/16; 75%) have lived in endemic areas or have maintained sexual relations with natives of them. Four patients were diagnosed with TSP, three with ATL and another with lymphomatoid granulomatosis and angiocentric T-cell lymphoma. The remaining patients were asymptomatic at the time of diagnosis. Two HTLV-I carriers were identified on blood donation. HTLV-I infection is present in Spain being found in Spanish natives and, to a lesser degree, in immigrants from endemic areas. It is therefore recommendable to analyze the cost-benefit of anti-HTLV-I screening in blood donors.


A packaged solution to the problems of testing arrhythmia control devices at implant.
A composite implantable arrhythmia control device (ACD) implements the functions of a bradycardia pacemaker, an antitachycardia pacemaker, a cardioverter, and a defibrillator in an integrated fashion. Given this broad spectrum of functionality, the implant testing for these devices can become a formidable endeavor requiring a large ensemble of expensive, complex support equipment, and a significant amount of time. However, if this procedure is not carried out correctly, the device might later fail to defibrillate. This article presents a unique packaging system for an ACD that allows the device to be used while it is still in its sterile package. The device may then be used during implant testing as the defibrillation test unit. This collapses the amount of support equipment that is required to just the ACD, its programmer, and an optional switch box. By providing additional support specifically for implant testing through the ACD programmer, implant testing may be reduced to a quick, easy-to-manage procedure. Since the device used during implant testing is the same device that will be implanted, this packaging system offers the further advantage that the physician can be confident that, once implanted, the ACD will function correctly.


Synthesis, cytotoxicity, DNA binding and apoptosis of rhein-phosphonate derivatives as antitumor agents.
Several rhein-phosphonate derivatives (5a-c) were synthesized and evaluated for in vitro cytotoxicity against HepG-2, CNE, Spca-2, Hela and Hct-116 cell lines. Some compounds showed relatively high cytotoxicity. Especially compounds 5b exhibited the strongest cytotoxicity against HepG-2 and Spca-2 cells (IC50 was 8.82 and 9.01 µM), respectively. All the synthesized compounds exhibited low cytotoxicity against HUVEC cells. Further experiments proved that 5b could disturb the cell cycle in HepG-2 cells and induce apoptosis. In addition, the binding properties of a model conjugate 5b to DNA were investigated by methods (UV-Vis, fluorescence, CD spectroscopy). Results indicated that 5b showed moderate ability to interact ct-DNA.


Small animal PET in oncology: the road from bench to bedside.
Positron emission tomography (PET) is routinely performed in patients with cancer for disease staging, assessment of relapse, and evaluation of therapy response. In addition to its well-established value in human malignant diseases, the use of special small animal PET (SA-PET) scanners have allowed for accurate assessment of small animals bearing human tumors. This application of PET provides whole-body, noninvasive, functional data of tumor lesions and can be used to assess abnormalities in the metabolic pathways of cancer, such as uncontrolled proliferation, increased apoptosis, and angiogenesis. Several positron-emitting tracers labeled with 18-fluorine and 11-carbon are currently available for PET studies to image abnormal biologic pathways of tumors. Moreover, SA-PET can be used to evaluate tumor-cell-receptor expression, a sign of tumor cells differentiation that is relevant for planning targeted therapies. Another advantage of SA-PET is the quantitation capability: Semiquantitation of the tumor activity can be performed at each scan and compared in the same animal over time to monitor tumor growth or to assess the response to new therapies. This review focuses on the applications of SA-PET for the visualization of the pathophysiologic pathways of tumor cells.


Evolutionary determinants of normal arterial plasma pH in ectothermic vertebrates.
Mean values of normal arterial pH in different species of fish, amphibians and reptiles at 15 and 25 degrees C, taken from the literature, are negatively correlated with arterial P(CO(2)) and plasma [Na(+)]. At either temperature, the data accord with the hypothesis that extracellular acid-base homeostasis evolved to maintain an optimal pH at particular cell-surface sites that are similar in all species. These hypothetical sites bear fixed negative charges that attract H(+), but which are partially screened by Na(+); for the surface pH to be constant, the bulk interstitial pH should then vary inversely with [Na(+)], as is the case. At the same time, the bulk interstitial fluid must be more acid than arterial plasma by an amount that increases with decreasing arterial P(CO(2)). With allowance made for additional screening by Ca(2+) and Mg(2+), the relevant cell-surface pH is probably approximately 6.2.


Use of the relative release index for histamine in LAD2 cells to evaluate the potential anaphylactoid effects of drugs.
Anaphylactoid reactions are common clinical acute adverse drug reactions that can exacerbate a patient's condition and produce effects that may become life-threatening. Therefore, it is important to establish a novel method to evaluate drugs for anaphylactoid reactions. In this study, we developed a sensitive and rapid method to detect histamine release from LAD2 cells using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and constructed a relative release index based on various release curve parameters, including allergen release time and sudden change rate, to evaluate the potential and strength of allergen-induced anaphylactoid reactions. This LAD2 release model was used to evaluate anaphylactoid reactions induced by ciprofloxacin, norfloxacin, lomefloxacin, moxifloxacin, and baicalin. The results positively correlated with those obtained with an Evans blue ear test and negatively correlated with the Ca2+ influx EC50. In summary, the current study established a novel in vitro method to analyze the properties of histamine release from LAD2 cells and characterize the sensitization and strength of sensitization of drugs or components that may induce anaphylactoid reactions.


Comparison of remedial and compensatory approaches in memory dysfunction: a comprehensive literature review.
ABSTRACT Memory is a cognitive process of information storage and retrieval that is essential to performing daily functional activities efficiently. Occupational therapists regularly help individuals with memory impairment to manage their memory deficits. The purpose of this paper was to review the main memory strategies and instructional methods used to improve or manage memory. Studies were identified by searching for the relevant literature published between 1980 and 2007 through the use of several databases with the inclusion criteria that the study must identify at least one specific memory rehabilitation method with an outcome measure representative of the specific method. The reviewed studies included three reviews, 10 randomized control trials, 17 quasi-experimental studies, and five single subjects' designs. The results suggest that there is empirical evidence to support the effectiveness of certain remedial and compensatory memory rehabilitation methods with healthy populations, but weaker evidence can be identified for the memory-impaired populations. In general, remedial methods are effective in lab settings with primarily healthy populations, yet effectiveness in daily activities is less clear. Compensatory methods are generally more efficient than remedial ones and more easily generalized to daily activities, even with memory-impaired populations.


Recent demographic and migratory trends among Soviet Jews: implications for policy.
The author examines recent demographic trends concerning the Jewish population of the former USSR, with consideration given to both internal and international migration. "Among the factors whose effects on population dynamics are examined, emphasis is placed on the Jewish population's concentration in large urban areas, the effects of emigration on age structure of the remaining population, self-identification as a method in census enumeration, ethnic intermarriage and family characteristics, and the outlook and prospects for emigres in Israel and the United States." The effect of Soviet state policy on Jewish population dynamics is also considered.


[Recent advances in the study of AMPK and inflammatory pulmonary disease].
AMP-activated protein kinase (AMPK) is an important regulator of cellular energy homeostasis. Recent studies demonstrated that AMPK is a novel signaling molecule modulating inflammatory responses and oxidative stress which are involved in inflammatory pulmonary diseases, such as asthma, chronic obstructive pulmonary disease (COPD), pulmonary infectious diseases and pulmonary fibrosis. AMPK attenuates inflammatory lung injury by phosphorylating its downstream targets, such as sirtuin1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha), p53 and forkhead box O3a (FoxO3a). This review summarized the relationship between AMPK and the development of inflammatory pulmonary diseases.


Changes in Serum NT-Pro BNP and Left Atrial BNP Levels after Percutaneous Transvenous Mitral Commissurotomy in Sinus Rhythm Versus Atrial Firilation.
Natriuretic peptides are secreted from the heart in response to increased wall stress. Their levels are expected to be increased in patients with mitral stenosis (MS) due to high left atrium (LA) pressure and pulmonary artery pressure (PAP). Percutaneous transvenous mitral commissurotomy (PTMC) if successful is pursued by a rapid decrease in LA pressure and subsequent decrease in pulmonary artery pressure. The concurrent changes in natriuretic peptide levels could be affected with heart rhythm. Forty five patients with severe rheumatic MS undergoing PTMC were enrolled. We evaluated the serum NT-Pro BNP levels before and 24 hours after PTMC. BNP levels were also measured from the blood samples obtained from LA before and 20 minutes after the procedure. Changes in biomarkers were assessed based on heart rhythm and success of the procedure. While serum NT-Pro BNP levels showed significant decrease 24 hours after the procedure (P= 0.04), BNP levels taken 20 minutes after PTMC from LA were similar to their baseline concentrations (P= 0.26). NT-Pro BNP levels decreased 51.7±182.86 pg/ml for sinus rhythm (SR) and 123.4±520 pg/ml for atrial fibrillation (AF) (P= 0.68). Immediate changes in BNP levels did not predict the success of procedure probably due to the additional balloon inflation attempts in LA in several patients and half-life of BNP. BNP levels obtained later may be of more value considering the half-life of this marker. Heart rhythm was not found to influence the changes in biomarker levels. BNP and NT-pro BNP changes were not found to predict success of the procedure.