[Pulmonary sclerosing hemangioma: report of 15 cases and review of the literature].
To improve the understanding of pulmonary sclerosing hemangioma (PSH). The clinical data of 15 cases of PSH were analyzed, and the literature was reviewed. The etiology, clinical manifestations, differential diagnosis, treatment and outcome of PSH were described. The etiology and histological origin of PSH were unclear. Most cases were asymptomatic or only with mild symptoms. The radiology of PSH often showed isolated nodule with distinct margin in the lung field. The characteristics of its pathological manifestation were as follows: (1) background of cell gathering or mucin matrix with scattered white blood cells; (2) proliferation of hemangioma with sclerosis of vessel wall; (3) papillary proliferation of small vessels intruding into the air space; (4) existence of hemorrhage or sclerosis zone. Immunohistological studies had not defined the correct histological origin of PSH. A pre-operation diagnosis of PSH was difficult. Thirteen cases had been misdiagnosed as malignancy. The outcome of the disease was good when early surgical resection was performed. PSH is an uncommon disease, and can be easily misdiagnosed. More attention should be paid to its clinical features and management.


Toenail selenium, plasma selenoprotein P and risk of advanced prostate cancer: A nested case-control study.
Low selenium status may be associated with increased risk of prostate cancer (PC), particularly aggressive PC, and variation in selenoprotein genes may constitute an important modifying factor. We aimed to investigate the association between two selenium status biomarkers [toenail selenium, plasma selenoprotein P (SELENOP)] and risk of advanced, high-grade and advanced-stage PC. We further studied whether variations in selenoprotein genes were associated with PC risk and selenium biomarker concentrations. In the "Diet, Cancer and Health" cohort, 27 178 men aged 50 to 65 years were enrolled from 1993 to 1997. Between baseline and 2012, 1160 cohort participants were diagnosed with advanced PC; among these 462 had high-grade and 281 had advanced-stage disease at diagnosis. Each case was risk set-matched to one control. Toenail selenium and plasma SELENOP concentrations were measured by neutron activation analysis and a SELENOP-ELISA, respectively, and genotyping was performed for 27 selected single nucleotide polymorphisms (SNPs) in 12 selenium pathway genes (including seven selenoproteins) by allele-specific PCR. Toenail selenium and circulating SELENOP concentrations were not associated with advanced, high-grade or advanced-stage PC. After adjustment for multiple testing, none of the genes were associated with PC risk. Neither toenail selenium nor plasma SELENOP was associated with advanced, high-grade or advanced-stage PC.


Does melatonin induce apoptosis in MCF-7 human breast cancer cells in vitro?
Melatonin inhibits proliferation of the estrogen-responsive MCF-7 human breast cancer cells. The objective of this work was to assess whether melatonin not only regulates MCF-7 cell proliferation but also induces apoptosis. In this experiment we used 1,25-dihydroxycholecalciferol (D3) as a positive control because it inhibits MCF-7 cell proliferation and induces apoptosis. MCF-7 cells were cultured with either I nM melatonin, 100 nM D3 or its diluent to determine their effects on cell proliferation, cell viability, cell-cycle phase distribution, population of apoptotic cells, and expression of p53, p21WAF1, bcl-2, bcl-X(L) and bax proteins. After 24 or 48 hr of incubation, both melatonin and D3-treatment significantly decreased the number of viable cells in relation to the controls, although no differences in cell viability were observed between the treatments. The incidence of apoptosis, measured as the population of cells falling in the sub-G1 region of the DNA histogram, or by the TUNEL reaction, was similar in melatonin-treated and control cells whereas, as expected, apoptosis was higher among cells treated with D3 than in controls. The expression of p53 and p21WAF1 proteins significantly increased after 24 or 48 hr of incubation with either melatonin or D3. No significant changes in bcl-2, bcl-XL and bax mRNAs were detected after treatment with melatonin whereas in D3-treated cells, a significant drop in bcl-XL was observed. These data support the hypothesis that melatonin reduces MCF-7 cell proliferation by modulating cell-cycle length through the control of the p53-p21 pathway, but without clearly inducing apoptosis.


First clinical results with a telemetric shunt-integrated ICP-sensor.
The telemetric shunt-integrated sensors available up to now do not deliver negative CSF pressure values. Therefore, a new sensor was designed which is incorporated into the shunt line proximally to the valve. The monitor calculates the pressure values in relation to the atmospheric pressure obtained by a built-in barometer. The sensor covers a pressure range of -100 cmH2O to 200 cmH2O with a resolution of +/- 1 cmH2O. First follow-up experiences are reported with seven patients over 14-17 months. Depending on the patient's body position telemetrically measured CSF-pressures varied between -20 cmH2O in erect and 15 cmH2O in supine position. In a patient with intermittent shunt dysfunction and stiff ventricular walls telemetrically measured CSF values corresponded earlier and were more sensitive with the clinical symptomatology than with the CT scan. So far, recognizable advantages of the telesensor are an improved assessment of shunt dysfunction and marginal CSF pressure increases, with practicability and simplicity of measurements in outpatients and a reduction of expensive CT or MRI controls.


Expression and phosphorylation of the Na+-Cl- cotransporter NCC in vivo is regulated by dietary salt, potassium, and SGK1.
The Na-Cl cotransporter NCC is expressed in the distal convoluted tubule, activated by phosphorylation, and has been implicated in renal NaCl and K(+) homeostasis. The serum and glucocorticoid inducible kinase 1 (SGK1) contributes to renal NaCl retention and K(+) excretion, at least in part, by stimulating the epithelial Na(+) channel and Na(+)-K(+)-ATPase in the downstream segments of aldosterone-sensitive Na(+)/K(+) exchange. In this study we confirmed in wild-type mice (WT) that dietary NaCl restriction increases renal NCC expression and its phosphorylation at Thr(53), Thr(58), and Ser(71), respectively. This response, however, was attenuated in mice lacking SGK1 (Sgk1(-/-)), which may contribute to impaired NaCl retention in those mice. Total renal NCC expression and phosphorylation at Thr(53), Thr(58), and Ser(71) in WT were greater under low- compared with high-K(+) diet. This finding is consistent with a regulation of NCC to modulate Na(+) delivery to downstream segments of Na(+)/K(+) exchange, thereby modulating K(+) excretion. Dietary K(+)-dependent variation in renal expression of total NCC and phosphorylated NCC were not attenuated in Sgk1(-/-) mice. In fact, high-K(+) diet-induced NCC suppression was enhanced in Sgk1(-/-) mice. The hyperkalemia induced in Sgk1(-/-) mice by a high-K(+) diet may have augmented NCC suppression, thereby increasing Na(+) delivery and facilitating K(+) excretion in downstream segments of impaired Na(+)/K(+) exchange. In summary, changes in NaCl and K(+) intake altered NCC expression and phosphorylation, an observation consistent with a role of NCC in NaCl and K(+) homeostasis. The two maneuvers dissociated plasma aldosterone levels from NCC expression and phosphorylation, implicating additional regulators. Regulation of NCC expression and phosphorylation by dietary NaCl restriction appears to involve SGK1.


Percolation in directed scale-free networks.
Many complex networks in nature have directed links, a property that affects the network's navigability and large-scale topology. Here we study the percolation properties of such directed scale-free networks with correlated in and out degree distributions. We derive a phase diagram that indicates the existence of three regimes, determined by the values of the degree exponents. In the first regime we regain the known directed percolation mean field exponents. In contrast, the second and third regimes are characterized by anomalous exponents, which we calculate analytically. In the third regime the network is resilient to random dilution, i.e., the percolation threshold is p(c)-->1.


[Clinicopathologic characteristics of primary central nervous system malignant lymphoma].
We examined 13 cases of the primary central nervous system malignant lymphoma (PCNSML) with established histological diagnosis and valid clinical information to clarify the clinicopathologic characteristics of PCNSML. All tumors were classified according to the World Health Organization as diffuse large B-cell lymphoma (DLBCL), and four were positive for CD 10 or BCL-6. All of the tumors had a high proliferative activity containing 15.7% to 84.8% (mean = 59.8%) MIB-1 positive cells, although there was no correlation between MIB-1 staining indices and the survival period of patients. Molecular analysis using PCR demonstrated clonal rearrangement of the IgH gene in the majority of cases analyzed (9/10 = 90%). Tumor cell apoptosis was consistently demonstrated by the routinely-processed histology and the immunohistochemistry for single-stranded DNA, and apoptotic cells were engulfed by phagocytic macrophages. These findings indicate that the majority of this series of PCNSML were DLBCL with high proliferative activity and clonal B-cell process and that a subset of the cases are of putative germinal center B-cell origin. Since there was no statistical correlation between the histopathological finding and the survival rate, additional studies, including quantitative investigation for the extent of apoptotic cells, in large numbers of patients are required.


Serial and semantic encoding of lists of words in schizophrenia patients with visual hallucinations.
Previous research has suggested that visual hallucinations in schizophrenia are associated with abnormal salience of visual mental images. Since visual imagery is used as a mnemonic strategy to learn lists of words, increased visual imagery might impede the other commonly used strategies of serial and semantic encoding. We had previously published data on the serial and semantic strategies implemented by patients when learning lists of concrete words with different levels of semantic organisation (Brébion et al., 2004). In this paper we present a re-analysis of these data, aiming at investigating the associations between learning strategies and visual hallucinations. Results show that the patients with visual hallucinations presented less serial clustering in the non-organisable list than the other patients. In the semantically organisable list with typical instances, they presented both less serial and less semantic clustering than the other patients. Thus, patients with visual hallucinations demonstrate reduced use of serial and semantic encoding in the lists made up of fairly familiar concrete words, which enable the formation of mental images. Although these results are preliminary, we propose that this different processing of the lists stems from the abnormal salience of the mental images such patients experience from the word stimuli.


Identifying model error in metabolic flux analysis - a generalized least squares approach.
The estimation of intracellular flux through traditional metabolic flux analysis (MFA) using an overdetermined system of equations is a well established practice in metabolic engineering. Despite the continued evolution of the methodology since its introduction, there has been little focus on validation and identification of poor model fit outside of identifying "gross measurement error". The growing complexity of metabolic models, which are increasingly generated from genome-level data, has necessitated robust validation that can directly assess model fit. In this work, MFA calculation is framed as a generalized least squares (GLS) problem, highlighting the applicability of the common t-test for model validation. To differentiate between measurement and model error, we simulate ideal flux profiles directly from the model, perturb them with estimated measurement error, and compare their validation to real data. Application of this strategy to an established Chinese Hamster Ovary (CHO) cell model shows how fluxes validated by traditional means may be largely non-significant due to a lack of model fit. With further simulation, we explore how t-test significance relates to calculation error and show that fluxes found to be non-significant have 2-4 fold larger error (if measurement uncertainty is in the 5-10 % range). The proposed validation method goes beyond traditional detection of "gross measurement error" to identify lack of fit between model and data. Although the focus of this work is on t-test validation and traditional MFA, the presented framework is readily applicable to other regression analysis methods and MFA formulations.


Quality of Life Assessment in Patients with Androgenetic Alopecia.
Male-pattern alopecia (MPA) or androgenetic alopecia (AGA) is a commonly encountered dermatological condition present in males and is less common among females. Although AGA is a physiological condition, its impact on person's self-esteem is so great that it cannot be ignored. It has a significant affect over a variety of physiological and social aspects of one's life and even on the individual's overall quality of life (QOL). The aim of this study is to study the clinical profile of 200 male patients having MPA and to access its impact on QOL using the Dermatology Life Quality Index (DLQI) and hair-specific Skindex-29. Clinical profiles of 200 patients were studied, and QOL assessment was done using the DLQI and hair-specific Skindex-29 scales. Of 200 cases of MPA, majority (41.5%) of the patients belonged to the age group of 21-30 years. Smoking, alcoholism, dietary habits, nature of work, and seasonal variation did not seem to affect the incidence of MPA. Positive family history of MPA was observed in 50% of patients. A mean DLQI score of 13.52 was recorded in the study. The main affected parameter was personal relations with mean score of 2.3. Maximum number of patients had DLQI score between 11 and 20. MPA was observed in 50% of patients. In the study, the mean hair-specific Skindex-29 score was found to be 75.62. The different subscale parameters in Skindex-29 were symptoms, functions, emotions; with respective score of 22.1 ± 5.025, 25.89 ± 4.814, and 27.73 ± 5.942. The major subscales affected were symptoms with a mean score of 3.14. Both hair-specific Skindex-29 and DLQI had a significant correlation, thereby suggesting that AGA significantly affects patient's QOL. AGA harmfully affected the patient's QOL which warns the physicians to pay more attention to QOL impairment in patients of AGA for the better understanding of the disease burden on individual patients.


Effect of Shear Bands Induced by Asymmetric Rolling on Microstructure and Texture Evolution of Non-Oriented 3.3% Si Steel.
In the present work, the microstructure and texture of non-oriented 3.3% Si steel processed by asymmetric rolling (ASR) and subsequent annealing at different temperatures were compared with those obtained when using traditional symmetric rolling (SR). This work aims to reveal the effect of shear bands introduced by the ASR on the microstructure and texture evolution. The ASR sample reaches a recrystallization fraction of 62% at an annealing temperature of 650 °C, which is 32% higher than that of the SR sample annealed at the same temperature. This can be attributed to the abundant shear bands introduced by the ASR, which serve as the heterogeneous nucleation sites for the recrystallized grains. When increasing the annealing temperature to 750 °C, complete recrystallization could be observed in both asymmetric- and symmetric-rolled samples. When using an annealing temperature of 650 °C, the γ-oriented grains were dominant in the surface layer, while strong Goss-oriented grains could be observed in the center in the ASR sample. This is due to the fragmented small subgrains with different orientations in the surface layer inhibiting the nucleation of Goss- and cube-oriented grains during the annealing. In contrast, numerous Goss- and cube-oriented grains were formed in the surface layer after complete recrystallization when the ASR sample was annealed at a temperature of 750 °C. This may be related to the higher thermal energy, which benefits the nucleation of the Goss- and cube-oriented grains. In addition, ASR significantly increased the strength of η-fiber after complete recrystallization when compared with SR. This work might be helpful to design the rolling and the subsequent annealing processes.


Intentions to work during terminal illness: an exploratory study of antecedent conditions.
Facing a terminal illness is an unimaginably difficult experience, yet many individuals intend to work despite their prognosis. However, research has not systematically examined the potential antecedents underlying such intentions. Using behavioral intention theory as an underlying framework, this study hypothesized that reasons for working (intrinsic and extrinsic), the will to live, disability severity, accessibility of travel, and age would predict intentions to work during terminal illness. A representative sample of medically diagnosed amyotrophic lateral sclerosis (a.k.a. Lou Gehrig's disease) patients with a mean life expectancy of approximately 3 years participated (mean age=57.8 years). Controlling for length of diagnosis, employment status, and demographic variables, results indicated that intrinsic reasons were particularly strong predictors of intentions, followed by age, disability severity, and accessibility of travel. Exploratory findings also indicated that behavioral intentions were positively related to future employment status, consistent with past theory. ((c) 2005 APA, all rights reserved).


Cold snare resection for the treatment of benign airway lesions.
The objective was to assess the safety and outcome of cold snare technique used by flexible bronchoscopy in the treatment of airway benign neoplasms. The clinical data of 21 patients, who had airway benign neoplasm and were treated through the cold snare method in Sir Run Run Shaw Hospital, affiliated with the Zhejiang University, were retrospectively analyzed. The relief of the symptoms and occurrence of complications were observed and evaluated. All the tumors were benign and removed by cold snare. Postoperatively, we found that the treatment was completely effective in 12 patients, and there was a significant improvement in 7 patients and a moderate improvement in 2 patients, and no recurrence in follow-up visit. In conclusion, the cold snare technique is an economically feasible, safe, and effective method in the treatment of airway neoplasms.


Genetic signature of natural selection in first Americans.
When humans moved from Asia toward the Americas over 18,000 y ago and eventually peopled the New World they encountered a new environment with extreme climate conditions and distinct dietary resources. These environmental and dietary pressures may have led to instances of genetic adaptation with the potential to influence the phenotypic variation in extant Native American populations. An example of such an event is the evolution of the fatty acid desaturases (FADS) genes, which have been claimed to harbor signals of positive selection in Inuit populations due to adaptation to the cold Greenland Arctic climate and to a protein-rich diet. Because there was evidence of intercontinental variation in this genetic region, with indications of positive selection for its variants, we decided to compare the Inuit findings with other Native American data. Here, we use several lines of evidence to show that the signal of FADS-positive selection is not restricted to the Arctic but instead is broadly observed throughout the Americas. The shared signature of selection among populations living in such a diverse range of environments is likely due to a single and strong instance of local adaptation that took place in the common ancestral population before their entrance into the New World. These first Americans peopled the whole continent and spread this adaptive variant across a diverse set of environments.


Polarotaxis and scototaxis in the supratidal amphipod Platorchestia platensis.
Talitrid amphipods use many cues for orientation during forays between temporary burrows and feeding areas, and for locating beaches when submerged, with visual cues being particularly important. Little evidence exists for polarized light among these visual cues despite extensive orientation by celestial and underwater polarized light in other crustaceans and in insects. We used electroretinography to assess spectral sensitivity in the eye of the beach flea Platorchestia platensis, and behavioral studies to test whether linearly polarized light serves as an orientation cue. Two spectral classes were present in the P. platensis eye with maxima at 431 and 520 nm. Non-uniform orientation of amphipods in the laboratory arena required either light/dark or polarized cues. Scototactic movements depended on arena conditions (day/night, wet/dry), while orientation under linearly polarized light was wavelength-dependent and parallel to the e-vector. Subsequent tests presented conflicting and additive scototactic and polarotactic cues to differentiate among these responses. In dry conditions, orientation parallel to the polarization e-vector overcame a dominant negative scototaxis, confirming that polarotaxis and scototaxis are separate orientation responses in this species. These behavioral results demonstrate talitrid amphipods can perceive and orient to linearly polarized light, and may use it to orient toward preferred zones on beaches.


Effects of 5,5-substitution on dipyrrolylmethane ligand isomerization.
The difference in steric profiles for eta(5) and eta(1)-pyrrolyls can be used to modify barriers for pyrrolyl exchange. The method investigated incorporated 1,3-diaxial interactions in a cyclohexyl backbone of the dipyrrolylmethane. Some of the enthalpic barrier created with the 1,3-steric interactions appears to be mediated by increased entropy in the ground state, but noticeable changes are produced in the pyrrolyl exchange rates by (1)H NMR without steric crowding at the metal center.


Overnight Alopecia: A Subtype of Acute Diffuse and Total Alopecia?
Acute diffuse and total alopecia (ADTA) is a variant of alopecia areata which lacks the typical patchy hair loss seen in classical alopecia areata and presents with an acute onset of diffuse hair loss commonly reported in young females with the duration from disease onset to diffuse hair loss ranging from 2 to 20 weeks. Although the clinical features of ADTA resemble telogen effluvium, dermoscopy can prove to be a useful tool for differentiating these two conditions and avoiding unnecessary investigations as specific dermoscopic findings of alopecia areata are invariably present along the disease course. Herein, we report a case of ADTA in a 42-year-old Indian female who presented with sudden onset of diffuse hair loss of only 1-day duration.


[Eosinophilia and dormant parasitosis].
The exotic diseases are still far from a daily preoccupation and sometimes face the physician with unusual problems. Two classical situations are reported: eosinophilia of parasitic origin, and three examples of asymptomatic parasitosis. Eosinophilia is a classical sign accompanying multicellular parasites (helminths). The rate depends on the duration of the disease, the type of parasite and the scale of the infestation. Pathological eosinophilia is usually present before diagnosis is possible; hence it is necessary to repeat laboratory examinations. Several parasitic diseases are asymptomatic and, after a long evolution, cause serious complications. Examples quoted are malaria, for which there is no absolute prophylaxis, amoebiasis, which is responsible for hepatic necrosis in patients who have never had dysentery, and schistosomiasis, which insidiously causes irreversible hepatic necrosis and ureteral stenosis. These conditions are becoming increasingly frequent in our countries and call for closer attention.


Pharmacological Benefits and Underlying Mechanisms of Salvia miltiorrhiza against Molecular Pathology of Various Liver Diseases: A Review.
Salvia miltiorrhiza Bunge, called Danshen in Chinese, is the dried root and rhizome of S. miltiorrhiza, which is part of the mint family, Lamiaceae; it has chiefly been used to treat blood stasis and improve blood flow in cerebrovascular and cardiovascular diseases for over 2000 years. Recent preclinical studies have indicated that S. miltiorrhiza has a wide range of pharmacological properties making it useful for the treatment of diverse liver diseases. S. miltiorrhiza protects the liver from harmful hepatotoxins, reduces hepatic oxidative stress, ameliorates steatosis, and alleviates hepatic inflammation, fibrosis, and cancer. Moreover, several key mechanisms, including apoptosis, AMP-activated protein kinase, mitogen-activated protein kinase, and nuclear factor kappa B, may be involved in the benefits of S. miltiorrhiza in hepatic disorders. In particular, salvianolic acid B and cryptotanshinone, both compounds derived from S. miltiorrhiza, possess therapeutic activities similar to those of S. miltiorrhiza, and thus may play a crucial role in the therapeutic activity of S. miltiorrhiza in liver diseases. Because reports on the pharmacological effects of this herb are scattered, this review aimed to consolidate the available literature to allow the re-evaluation and identification of gaps to guide future research. This review focuses on the role of S. miltiorrhiza in improving the molecular pathology of liver diseases, as reported in in vitro and in vivo studies.


Rab23: what exactly does it traffic?
Rab23 is the product of the gene mutated in the mouse open brain1 phenotype, which displays neural tube defects. It appears to antagonize sonic hedgehog (Shh)-mediated signaling during mouse development, presumably by regulating the intracellular trafficking of one or more of Shh's-signaling components. The Shh receptor Patched1 (Ptch1) and its downstream effector Smoothened (Smo) were initial prime suspects as they are membrane proteins whose cellular dynamics are modulated by the Shh signal. However, Rab23 mutants do not appear to affect the localization and dynamics of either protein. Genetic analyses have now shown that Rab23 functions downstream of Smo and affects the function of the Shh-regulated Gli family of transcription factors in a more direct manner than previously thought. A plethora of proteins that influence Shh signaling and whose cellular trafficking could potentially be regulated by Rab23 has also emerged. These include members of the intraflagellar transport complex, as well as motor proteins responsible for their assembly at the cilia. Rab23 is also expressed in adult mouse neurons and may thus have functions beyond embryonic developmental stages and Shh signaling. We discuss these new findings and explore the myriad of possibilities whereby Rab23 may function.


Trust in Medical Technology by Patients and Health Care Providers in Obstetric Work Systems.
Multiple types of users (i.e. patients and care providers) have experiences with the same technologies in health care environments and may have different processes for developing trust in those technologies. The objective of this study was to assess how patients and care providers make decisions about the trustworthiness of mutually used medical technology in an obstetric work system. Using a grounded theory methodology, we conducted semi-structured interviews with 25 patients who had recently given birth and 12 obstetric health care providers to examine the decision-making process for developing trust in technologies used in an obstetric work system. We expected the two user groups to have similar criteria for developing trust in the technologies, though we found patients and physicians differed in processes for developing trust. Trust in care providers, the technologies' characteristics and how care providers used technology were all related to trust in medical technology for the patient participant group. Trustworthiness of the system and trust in self were related to trust in medical technology for the physician participant group. Our findings show that users with different perspectives of the system have different criteria for developing trust in medical technologies.


Synthesis and DPPH radical scavenging activity of prenylated phenol derivatives.
The synthesis of twenty six prenylated phenols derivatives is reported. These compounds were obtained under mild conditions via Electrophilic Aromatic Substitution (EAS) coupling reactions between phenol derivatives containing electron-donor subtituents and 3-methyl-2-buten-1-ol using BF(3)×OEt(2). Dialkylations were also produced with this method. The formation of a chroman ring by intramolecular cyclization between a sp2 carbon from the prenyl group with the hydroxyl substituent in the ortho position occurred with some phenols. All the synthesized compounds were evaluated as antioxidants according to a DPPH radical scavenging activity assay. IC(50) values of five synthesized compounds indicated they were as good antioxidants as Trolox™.


Host responses to Renibacterium salmoninarum and specific components of the pathogen reveal the mechanisms of immune suppression and activation.
During infection, Renibacterium salmoninarum survives within the pronephric macrophages of salmonid fish. Therefore, to study the initial phases of the interaction we infected macrophages with live bacteria and analysed the responses of host and pathogen. It was found that the expression of msa encoding the p57 antigen of R. salmoninarum, was constitutive, while the expression of hly and rsh, encoding haemolysins, and lysB and grp was reduced after infection. Macrophages showed a rapid inflammatory response in which the expression of interleukin-1beta (IL-1beta), major histocompatibility complex class II (MHC II), inducible cyclo-oxygenase (Cox-2), and inducible nitric oxide synthase (iNOS) was enhanced, but tumour necrosis factor-alpha (TNF-alpha) expression was greatly reduced initially and then increased. After 5 days, except for TNF-alpha and MHC II, expression returned to levels approaching those of uninfected macrophages. We propose that R. salmoninarum survives initial contact with macrophages by avoiding and/or interfering with TNF-alpha-dependent killing pathways. The effects of specific R. salmoninarum components were studied in vivo by injecting fish with DNA vaccine constructs expressing msa, hly, rsh, lysB, or grp. We found that msa reduced the expression of IL-1beta, Cox-2, and MHC II but stimulated TNF-alpha while hly, rsh and grp stimulated MHC II but down-regulated TNF-alpha. Constructs expressing hly or lysB stimulated iNOS expression and additionally, lysB stimulated TNF-alpha. The results show how p57 suppresses the host immune system and suggest that the immune mechanisms for the containment of R. salmoninarum infections rely on MHC II- and TNF-alpha-dependent pathways. Moreover, prolonged stimulation of TNF-alpha may contribute to the chronic inflammatory pathology of bacterial kidney disease.


Two-input programmable optical processing units.
Descriptions of several two-input programmable Boolean optical processing units are presented. These units were designed specifically for use within the optical cellular logic image processor architecture. Results from an experimental implementation of one of these processors are given. Expansion upon one of these units to produce a serial full-adder and subtractor circuit is also shown to be possible.


Role of IL-8 rs4073 and rs2227306 polymorphisms in the development of primary gouty arthritis in a Chinese population.
In this study, we investigated the role of two single nucleotide polymorphisms in the promoter region of the interleukin-8 gene (IL-8; rs4073 and rs2227306) in the susceptibility to primary gouty arthritis in a Chinese population. Three hundred and twelve patients with primary gouty arthritis and 340 healthy controls were recruited from the Yan'an University Affiliated Hospital between January 2014 and March 2015. The IL-8 rs4073 and rs2227306 polymorphisms were genotyped by polymerase chain reaction combined with restriction fragment length polymorphism. Unconditional multiple-logistic regression analysis revealed that the TT genotype of rs4073 was correlated with primary gouty arthritis risk, compared to the AA genotype [adjusted odds ratio (OR) = 1.65, 95% confidence interval (CI) = 1.08-2.54; P = 0.02]. In addition, the IL-8 rs4073 T allele was associated with a significant elevated risk of primary gouty arthritis, in comparison to the A allele (OR = 1.34, 95%CI = 1.07-1.67; P = 0.01). However, we observed no significant relationship between the IL-8 rs2227306 polymorphism and primary gouty arthritis risk. The results of this study suggest that the IL-8 rs4073 polymorphism could be a marker for primary gouty arthritis development.


Simulation of oculomotility in Craniosynostosis patients.
Craniosynostosis syndromes can be associated with missing extraocular muscles, or muscles with abnormal insertions, and so provide useful test cases for assessing our understanding of the mechanics of the extraocular muscles. Patient with craniosynostosis syndromes often show eye movements in which a horizontal movement by one eye is accompanied by upshoot or downshoot in the other eye. An hypothesis which has been put forward to explain these movements is that the muscles in the patients are excyclorotated and that the upshoots and downshoots follow directly from the application of Hering's law of equal innervation. We modelled the mechanics of the excyclorotated muscles and verified this hypothesis. However, excyclorotation of the orbit often occurs in combination with anomalous muscle anatomy in craniosynostosis syndromes. In keeping with this finding, we have found that surgical transposition of the rectus muscles is insufficient by itself to correct the anomalous eye movements, but that transposition in combination with weakening of the obliques is effective.


Re-expansion of Thrombosed False Lumen after Aortic Dissection Due to Collateral Retrograde Flow from the Aortic Branches.
Re-expansion of thrombosed false lumen after aortic dissection due to collateral retrograde flow from the aortic branches has rarely been reported. Surgical or endovascular local management such as ligation or occlusion of culprit arteries may not be effective in case retrograde blood flow to the false lumen might occur again from another branch after the operation. Here, we report a 68-year-old woman with re-expansion of the thrombosed false lumen after acute type B aortic dissection due to collateral retrograde flow from the aortic branches successfully treated with tranexamic acid therapy and antihypertensive therapy.


Ketamine in chronic pain: A Delphi survey.
There is no recommendation in Europe for the use of ketamine in patients with chronic pain. The heterogeneity of practice highlights the need to seek the advice of experts in order to establish a national consensus. This Delphi survey aimed to reach a national consensus on the use of ketamine in chronic pain in Pain clinics. A collaborative four-round internet-based questionnaire was used. It was created after literature search on ketamine administration in chronic pain and included about 96 items. It discussed utility and advantages, adverse events and deleterious aspects, methods of administration, concomitant treatments and assessment of results. Twenty-eight experts completed all rounds of the survey with a total of 81.3% items reaching a consensual answer. Neuropathic pain represents the first indication to use ketamine, followed, with a good to moderate utility, by other situations (fibromyalgia, complex regional pain syndrome, central neuropathic pain, peripheral neuropathic pain, nociceptive pain, sensitization, opioid withdrawal, palliative care, depression). Experts agreed on the rare occurrence of adverse events. Concerning routes of administration, intravenous infusion with doses of 0.5-0.9 mg/kg/d for 4 days of treatment is preferred. Place of care is hospital, as in- or out-patient, with a quarterly administration of ketamine. Finally, ketamine effectiveness is assessed 1 month after infusion, and experts encourage combination with non-pharmacological treatment. This Delphi survey established a consensus of pain specialists on the use of ketamine in refractory chronic pain, thus providing a basis for future comparative trials. This Delphi survey in chronic pain reached agreement on four main aspects: (1) Priority to treat neuropathic pain with evaluation of effectiveness at 1 month; (2) No deleterious effects in the majority of listed diseases/situations with the absence or <3% of suggested adverse events; (3) 0.5-0.9 mg/kg/d IV infusion; (4) Combination with non-pharmacological treatment.


Efficacy of Rubus coreanus Miq. and Astragalus membranaceus Bunge Extract for Postmenopausal Syndrome: A Randomised, Double-Blind, Placebo Comparative Clinical Trial.
The most effective way to improve menopausal symptoms is to supplement deficient oestrogen; however, long-term administration of synthetic oestrogen increases the risk for breast and uterine cancers. Here, we report results from a clinical trial of Rubus coreanus Miq. and Astragalus membranaceus Bunge as agents for improving the menopause syndrome. This study was a single-centre, double-blinded, parallel-group, placebo-controlled study. The efficacy of an extract of R. coreanus Miq. and A. membranaceus Bunge was investigated. Participants were females with postmenopausal syndrome in the menopausal or menopausal transition period. The primary endpoint of validation was improvement in the Kupperman index (KI) score of women. The secondary end point was change in the Menopause Rating Scale (MRS) and lipid profile. The participants were randomly allocated at a 1 : 1 ratio into R. coreanus Miq. and A. membranaceus Bunge extract (RCAM) or placebo groups and were administered 2000 mg of the extract or placebo, respectively, daily for 12 weeks. Outcomes were measured at visits 2 (day 0) and 5 (week 12). The RCAM group demonstrated decreased KI score and MRS compared with the placebo group after 12 weeks. In the safety evaluation, laboratory tests and vital signs demonstrated no clinically significant changes in subjects, and there was no difference in adverse reactions between the groups. The R. coreanus Miq. and A. membranaceus Bunge extract was effective in reducing postmenopausal symptoms in women. Moreover, the extract was found to be safe. For females with menopausal symptoms in the menopausal transitional and postmenopausal periods, ingestion of the R. coreanus Miq. and A. membranaceus Bunge extract for 12 weeks was effective, as demonstrated by a decrease in KI score and MRS relative to that in the placebo group, and significantly improved the menopausal symptoms.


The causes of difficult tracheal intubation and preoperative assessments in different age groups.
We studied the differences in airway assessment factors among old, middle, and young age groups, and evaluated the frequency and causes of difficult intubation among these groups. Patients were divided into young (< 40 yr, n = 75 ), middle (40-59 yr, n = 83), and old (≥ 60 yr, n = 89) group. Airway assessment factors such as head and neck movement, thyromental distance, interincisor gap, dentition, Mallampati score, and Arné score were assessed. After muscle relaxation, cervical joint rigidity and Cormack-Lehane (C-L) grade were assessed. The differences in airway assessment factors between difficult (C-L grade 3, 4) and easy (C-L grade 1, 2) intubation were then examined. Logistic regression analysis was also carried out to identify the extent to which airway assessment factors reflected difficult intubation. As aging, head and neck movement, thyromental distance, and interincisor gap decreased, the grade of dentition, Mallampati score, cervical joint rigidity and the ratio of Arné score > 11 increased. In the old and middle group, the incidence of difficult intubation was increased compared with the young group. Dentition in the young group, Mallampati score and interinsisor gap in the middle group and Mallampati score, cervical joint rigidity in the old group respectively predicted difficult intubation. Compared to young individuals, middle-aged or elderly adults are likely to experience more difficulty in endotracheal intubation and its predictive factors could vary by age group.


Epithelial mediated wound contraction in experimental wounds--the purse-string effect.
Wound contraction, a process whereby wound edges are drawn together, is thought to be mediated by the myofibroblast cell population. However, experimental wounds may close as much as 25% (surface area) before the onset of fibroplasia which is marked by the migration of fibroblasts and myofibroblasts into the wound bed 2 to 3 days after injury. This early phase of wound closure appears to be mediated by a contractile force produced by a circumferentially arranged band of fusiform-shaped epidermal cells situated in the wound margin. Cytoplasmic microfilaments in the epidermal cells, similar in size and configuration to actin filaments and/or tonofilaments, are found to be aligned with the long axis of the constitutive cells comprising the contractile band. The data suggest that contraction in experimental wounds is promoted by at least two distinct cell-mediated contractile events: an initial although brief phase effected by cells of the epidermis followed by an extended phase of soft connective tissue contraction produced vis à vis the myofibroblasts in the dermis.


Sirolimus early graft nephrotoxicity: clinical and experimental data.
Sirolimus (SRL) is a recently available immunosuppressive agent. SRL, is a macrolide isolated from Streptomyces hydroscopicus that, in complex with its cellular receptor, FK binding protein, potently inhibits downstream signaling by the mammalian target of rapamycin (mTOR). It has been shown to reduce the incidence of acute rejection episode after renal transplantation. SRL by itself does not seem to cause significant nephrotoxicity in most animals and human studies in normal conditions. However, when combined with calcineurin inhibitors, serum creatinine levels often increase. The mechanisms for the synergism of this side-effect are still discussed. Furthermore, recent clinical data have shown that the administration of SRL immediately after renal transplant delay the recovery from delayed graft function. This effect may be secondary to the inhibition of the proliferation of the renal tubular cells which is a normal process for tubular repair. Some experimental data have confirmed this hypothesis. Finally, in the long-term, SRL use has been associated with a significant increase of proteinuria which may in the long-term increase the risk of graft loss of cardio-vascular morbio-mortality. For all these reasons, SRL nephrotoxicty has become an important issue after renal transplantation. The review will discuss the clinical and the experimental data regarding this complication, which has been underestimated.


Interaction of human estrogen receptors alpha and beta with the same naturally occurring estrogen response elements.
Estrogen receptors are derived from two different gene products referred to as estrogen receptor-alpha (ER-alpha) and ER-beta. Both receptors bind to the consensus estrogen response element (ERE) present in the vitellogenin gene, but their binding to hormone response elements present in other estrogen responsive genes has not been reported yet. Using in vitro expressed human receptors, we now show that ER-beta binds to a panel of six endogenous hormone response elements (vitellogenin, c-fos, c-jun, pS2, cathepsin D, and choline acetyltransferase) already known to bind ER-alpha and confer estrogen inducibility to reporter constructs. Binding of ER-alpha and ER-beta occurred at similar DNA concentrations for some EREs, but different DNA concentrations were required to form complexes of the two receptors with other elements. These results illustrate for the first time by direct receptor-DNA binding studies that both ER-alpha and ER-beta bind to a number of EREs present in endogenous hormone regulated genes, and further suggest that the two forms of the receptor display different patterns of affinities for naturally occurring hormone response elements.


Mindfulness-Based Cognitive Therapy for Trichotillomania: A Bayesian Case-Control Study.
Over the last years, mindfulness-based interventions combined with habit reversal training have been demonstrated to be particularly suitable for addressing trichotillomania. However, because these studies always combined mindfulness training to habit reversal without including either a mindfulness or habit reversal condition alone, it is still unclear whether clinical benefits are the consequences of mindfulness or merely result from habit reversal training. The primary purpose of the present study was thus to examine whether a mindfulness training procedure without habit reversal could alleviate trichotillomania. Using a Bayesian probabilistic approach for single-case design, client's hair loss severity and level of mindfulness were compared to a normative sample (n = 15) before treatment, after treatment, and at six-month follow-up. Improvement in mindfulness first occurred, and that beneficial effect then transferred to hair-pulling. Indeed, as compared to the normative sample, the client exhibited, from baseline to post-treatment, an improvement in mindfulness. Although a marginal trend to improvement was already evidenced at post-treatment, the mindfulness program only had a significant beneficial effect transferred to hair-loss severity at six-month follow-up. Although it remains particularly difficult to infer generalization from one client, the data from the present case study are the first to suggest that mindfulness training per se might be a suitable clinical intervention for trichotillomania.


Differential translation of the genes encoding the proton-translocating ATPase of Escherichia coli.
Translation of the gene for the b subunit of the Escherichia coli proton-translocating ATPase has been examined. Oligonucleotide-directed site-specific mutagenesis was used to mutate certain nucleotides in the intergenic region between uncE (c) and uncF (b). One of the changes was predicted to lower the stability of a proposed stem structure which blocked the ribosome binding site of the uncF mRNA segment. The result of the mutation is a nearly 3-fold increase in the rate of synthesis of the b polypeptide. Another mutation was introduced which changed the initiation codon for uncF from GUG to AUG. This change resulted in an approximately 2-fold increase in the synthesis rate of the b polypeptide. These results suggest that secondary structure in the mRNA and the use of a less efficient initiation codon play a role in restricting translation initiation of the uncF mRNA segment. These mechanisms may, in part, explain how the polypeptides of the ATPase complex are synthesized in approximately the same relative amounts as they appear in the assembled complex.


The surgical treatment of brachial plexus injuries.
Brachial plexus injuries cause a devastating loss of function in the arm. The aim of this study was to review the results of surgical treatment of patients with brachial plexus injuries. Forty-seven patients were reviewed. Five patients did not undergo surgery. Forty-two patients had exploration and 38 had primary surgery with neurolysis, nerve graft or neurotization or a combination. Four patients had other reconstructive surgery primarily. Secondary reconstructive surgery consisted of joint fusions and tendon transfers to enhance or replace the primary surgery. Nerve grafting achieved 62% Medical Research Council (MRC) grade M3 or better. Intercostal neurotization (ICN) of the musculocutaneous nerve (MCN) for elbow flexion achieved M3 or better in 69% of patients. Primary nerve reconstruction, combined with joint fusions and tendon transfers, provides a worthwhile return of function to many patients. We advise early exploration (i.e. within 2 weeks when possible) for patients with complete C5-T1 lesions or C5,6,7 lesions in conjunction with high energy injuries. In order to obtain optimal results patients with brachial plexus injuries should be referred to appropriate units as early as possible.


Management of Maxillofacial Gunshot Injuries With Emphasis on Damage Control Surgery During the Yemen Civil War. Review of 173 Victims From a Level 1 Trauma Hospital in Najran, Kingdom of Saudi Arabia.
Studies on the concept of Damage Control Surgery (DCS) in the management of firearm injuries to the oral and maxillofacial region are still scarce, hence the basis for the current study. The objectives of the current study is to share our experience in the management of maxillofacial gunshot injuries with emphasis on DCS and early definitive surgery. This was a retrospective study of combatant Yemeni patients with maxillofacial injuries who were transferred across the border from Yemen to Najran, Kingdom of Saudi Arabia. Demographics and etiology of injuries were stored. Paths of entry and exit of the projectiles were also noted. Also recorded were types of gunshot injury and treatment protocols adopted. Data was stored and analyzed using IBM SPSS Statistics for Windows Version 25 (Armonk, NY: IBM Corp). A total of 408 victims, all males, were seen during the study period with 173 (42.4%) males sustaining gunshot injuries to the maxillofacial region. Their ages ranged from 21 to 56 years with mean ± SD (27.5 ± 7.6) years. One hundred and twenty-one (70.0%) victims had extraoral bullet entry, while 53 (30.0%) victims had intraoral entry route. Ocular injuries, consisting of 25 (14.5%) cases of ruptured globe and 6 (3.5%) cases of corneal injuries, were the most commonly associated injuries. A total of 78 (45.1%) hemodynamically unstable victims had DCS as the adopted treatment protocol while early definitive surgery was carried out in 47(27.2%) hemodynamically stable victims. ORIF was the treatment modality used for the fractures in 132 (76.3%) of the victims. We observed that 42.4% of the war victims sustained gunshot injuries. DCS with ORIF was the main treatment protocol adopted in the management of the hemodynamically unstable patients.


Integrin alpha IIb beta 3 (platelet GPIIb-IIIa) recognizes multiple sites in fibronectin.
The binding of fibronectin (Fn) to several integrins involves the Arg-Gly-Asp (RGD) tripeptide sequence. However, linear synthetic RGD peptides do not completely mimic the cell attachment activity of intact Fn or certain large Fn fragments. This suggests that the integrin-Fn interaction involves a more extended surface of Fn than that provided by the RGD sequence. To test this possibility, three novel monoclonal anti-Fn antibodies that inhibit its binding to a purified integrin, alpha IIb beta 3, were developed. The epitopes of these three antibodies mapped to a region at least 55 residues amino-terminal of the RGD sequence. Further, recombinant fragments of Fn containing these epitopes and lacking the RGD site also inhibited the binding of Fn to purified alpha IIb beta 3. These fragments, which spanned Fn residues 1359-1436, bound to alpha IIb beta 3 in a divalent cation-dependent manner. In addition, this region of Fn bound specifically to alpha IIb beta 3 on thrombin-stimulated but not resting platelets. These results demonstrate the presence of additional sequences in Fn that interact with integrin alpha IIb beta 3 and suggest that multiple sites in Fn are involved in its recognition by this integrin.


Efficacy of Acute Intermittent Hypoxia on Physical Function and Health Status in Humans with Spinal Cord Injury: A Brief Review.
Spinal cord injury (SCI) results in a loss of motor and sensory function and is consequent with reductions in locomotion, leading to a relatively sedentary lifestyle which predisposes individuals to premature morbidity and mortality. Many exercise modalities have been employed to improve physical function and health status in SCI, yet they are typically expensive, require many trained clinicians to implement, and are thus relegated to specialized rehabilitation centers. These characteristics of traditional exercise-based rehabilitation in SCI make their application relatively impractical considering the time-intensive nature of these regimens and patients' poor access to exercise. A promising approach to improve physical function in persons with SCI is exposure to acute intermittent hypoxia (IH) in the form of a small amount of sessions of brief, repeated exposures to low oxygen gas mixtures interspersed with normoxic breathing. This review summarizes the clinical application of IH in humans with SCI, describes recommended dosing and potential side effects of IH, and reviews existing data concerning the efficacy of relatively brief exposures of IH to modify health and physical function. Potential mechanisms explaining the effects of IH are also discussed. Collectively, IH appears to be a safe, time-efficient, and robust approach to enhance physical function in chronic, incomplete SCI.


Randomized Trial of Verubecestat for Prodromal Alzheimer's Disease.
Prodromal Alzheimer's disease offers an opportunity to test the effect of drugs that modify the deposition of amyloid in the brain before the onset of dementia. Verubecestat is an orally administered β-site amyloid precursor protein-cleaving enzyme 1 (BACE-1) inhibitor that blocks production of amyloid-beta (Aβ). The drug did not prevent clinical progression in a trial involving patients with mild-to-moderate dementia due to Alzheimer's disease. We conducted a randomized, double-blind, placebo-controlled, 104-week trial to evaluate verubecestat at doses of 12 mg and 40 mg per day, as compared with placebo, in patients who had memory impairment and elevated brain amyloid levels but whose condition did not meet the case definition of dementia. The primary outcome was the change from baseline to week 104 in the score on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB; scores range from 0 to 18, with higher scores indicating worse cognition and daily function). Secondary outcomes included other assessments of cognition and daily function. The trial was terminated for futility after 1454 patients had been enrolled; 485 had been assigned to receive verubecestat at a dose of 12 mg per day (the 12-mg group), 484 to receive verubecestat at a dose of 40 mg per day (the 40-mg group), and 485 to receive placebo. A total of 234 patients, 231 patients, and 239 patients per group, respectively, completed 104 weeks of the trial regimen. The estimated mean change from baseline to week 104 in the CDR-SB score was 1.65 in the 12-mg group, 2.02 in the 40-mg group, and 1.58 in the placebo group (P = 0.67 for the comparison between the 12-mg group and the placebo group and P = 0.01 for the comparison between the 40-mg group and the placebo group), suggesting a worse outcome in the higher-dose group than in the placebo group. The estimated rate of progression to dementia due to Alzheimer's disease was 24.5, 25.5, and 19.3 events per 100 patient-years in the 12-mg group, the 40-mg group, and the placebo group, respectively (hazard ratio for 40 mg vs. placebo, 1.38; 97.51% confidence interval, 1.07 to 1.79, not adjusted for multiple comparisons), favoring placebo. Adverse events were more common in the verubecestat groups than in the placebo group. Verubecestat did not improve clinical ratings of dementia among patients with prodromal Alzheimer's disease, and some measures suggested that cognition and daily function were worse among patients who received verubecestat than among those who received placebo. (Funded by Merck Sharp & Dohme; ClinicalTrials.gov number, NCT01953601.).


Poetry in practice.
In the lull before the storm of challenging public service reconfigurations and rethinks, it is worth considering where both health professionals and patients can gain solace at no cost to the services.


Evaluation of the Mini-Mental State Examination and the Montreal Cognitive Assessment for Predicting Post-stroke Cognitive Impairment During the Acute Phase in Chinese Minor Stroke Patients.
Objective: To assess the value of the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) during acute phase in predicting post-stroke cognitive impairment (PSCI) at 3-6 months. Methods: We prospectively recruited 229 patients who had suffered their first-ever ischemic stroke. PSCI was determined in 104 of these patients by a comprehensive neuropsychological battery performed at 3-6 months. Receiver operating characteristic (ROC) curve analysis was then performed to compare the discriminatory ability of the MMSE and MoCA. Also, we applied a decision tree generated by the classification and regression tree methodology. Results: In total, 66 patients had PSCI when evaluated 3-6 months after the onset of minor stroke. Logistic regression analysis revealed that education, body mass index (BMI), and baseline MoCA scores were independently associated with PSCI. ROC curve analysis showed that the ability to predict PSCI was similar when compared between baseline MoCA scores [area under curve (AUC), 0.821; 95% confidence interval (CI), 0.743-0.898] and baseline MMSE scores (AUC, 0.809; 95% CI, 0.725-0.892, P = 0.75). Both MMSE and MoCA exhibited similar predictive values at their optimal cut-off points (MMSE ≤27; sensitivity, 0.682; specificity, 0.816; MoCA ≤21; sensitivity, 0.636; specificity, 0.895). Classification and regression tree-derived analysis yielded an AUC of 0.823 (sensitivity, 0.803; specificity, 0.842). Conclusion: When applied within 2 weeks of stroke, the MMSE and MoCA are both useful and have similar predictive value for PSCI 3-6 months after the onset of minor stroke.


[Characterization of human immature T cell precursors in fetal liver and postnatal thymus].
The sequence of events that accompany development of immature T cell precursors in man is not precisely known. Recently, we identified subpopulations of thymocytes that may represent intermediate stages between CD3-CD4-CD8- (TN) and CD3+CD4+CD8+ (DP) thymocytes. Multicolor analysis provided evidence for the existence of CD3-CD4+CD8- and CD3-CD4+CD8 alpha+beta- populations. In vitro culture of TN thymocytes with IL-7 gave rise to cells of these phenotypes, suggesting that the novel subpopulations we found are the progeny of TN thymocytes. Expression of CD34 was detected on most of TN thymocytes and progressively reduced as cells differentiate. The novel subpopulations were shown to express CD34. 6-22-week-old human fetal liver cells were also analyzed in search for the possible prethymic T cell precursors. It was revealed that most of CD3-CD7+ cells which had been considered as T cell precursors were CD34-CD56+ and exhibited non-MHC-restricted cytotoxicity. Thus, although they expressed cytoplasmic CD3 antigens, these cells seemed to represent NK cells rather than T cell precursors. Existence of the latter is still to be demonstrated.


Serotonin Analogues as Inhibitors of Breast Cancer Cell Growth.
Serotonin (5-hydroxytryptamine, 5-HT) is a critical local regulator of epithelial homeostasis in the breast and exerts its actions through a number of receptors. Dysregulation of serotonin signaling is reported to contribute to breast cancer pathophysiology by enhancing cell proliferation and promoting resistance to apoptosis. Preliminary analyses indicated that the potent 5-HT1B/1D serotonin receptor agonist 5-nonyloxytryptamine (5-NT), a triptan-like molecule, induced cell death in breast cancer cell lines. Thus, we synthesized a series of novel alkyloxytryptamine analogues, several of which decreased the viability of various human cancer cell lines. Proteomic and metabolomic analyses showed that compounds 6 and 10 induced apoptosis and interfered with signaling pathways that regulate protein translation and survival, such as the Akt/mTOR pathway, in triple-negative breast cancer cells.


Laboratory variables as additional staging parameters in patients with small-cell lung carcinoma. A systematic review.
We have reviewed the biomedical literature published over the last 25 years in order to try to establish which of four frequently evaluated laboratory parameters (i.e. serum, or plasma, NSE, LDH, sodium or albumin) might, alone or in combination, give the "best" pretreatment prognostic information in small-cell lung cancer (SCLC) patients, independent of the usual radiological and clinical parameters. From the 45 studies included in this review, the only clear conclusion that can be derived is that it has not yet been clearly demonstrated that the "new" tests (NSE or other tumor markers) are superior to the "old" tests (LDH, sodium, albumin etc.). From the only seven studies that used the same powerful statistical methodologies (Cox's models in association with recursive partitioning and amalgamation procedure (RECPAM) analysis) it could be concluded that LDH and albumin might have independent prognostic significance in SCLC and in advanced SCLC respectively. Provided that, in the future, both laboratory and statistical expertises are clearly guaranteed in the primary studies in this field, it might become possible to propose laboratory parameters as additional staging parameters in SCLC.


Behavioral practices of patients with multiple sclerosis during Covid-19 pandemic.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in late 2019 and Covid-19, a disease caused by SARS-CoV-2 became a pandemic in March 2020. As the pandemic still unfolds, uncertainty circles around the impact of SARS-CoV-2 infection on patients with chronic diseases, including autoimmune diseases such as multiple sclerosis (MS). To diminish the risk of SARS-CoV-2 infection and lessen the impact of the Covid-19 pandemic on the healthcare of MS patients, it is essential to understand knowledge, attitudes, and various behavioral practices related to Covid-19 among MS patients. Therefore, this study aimed to look at the behavioral practices related to Covid-19 among patients with MS. A total of 176 MS patients diagnosed at least one year before the survey were conveniently sampled online in Saudi Arabia and their data collected using a structured interview questionnaire in electronic Google form. We determined the reliability of the questionnaire by measuring its internal consistency in a pilot sample of 30 participants. Overall, more than 80% of participants had good knowledge and attitudes towards Covid-19. However, this did not correlate well with the impact on healthcare (r = 0.06). Our study revealed that 46% of participants were anxious about taking their medication, and 32% of participants missed their hospital appointments. Furthermore, 15% of the participants had a relapse but did not go to the hospital because of the pandemic, 15.9% stopped their DMTs, and 35.2% missed drug infusions or refills. Our study revealed overall good knowledge and attitudes related to Covid-19 among MS patients. However, the healthcare impact was considerable, as 32% of the participants missed their hospital appointments, and another 15% had a relapse. This highlights the significance of the impact of the Covid-19 pandemic on the healthcare of patients with MS. Measures to mitigate the effect of the pandemic on healthcare service delivery to patients with MS, such as telemedicine, should be strongly encouraged.


Study on the Cultivation of College Students' Internet Literacy in Ideological and Political Teaching under the Application of Virtual Reality Technology.
People are living in an age of artificial intelligence. Artificially intelligent technology, such as virtual reality technology, is creating new horizons in every field. In this article, people are learning about the cultivation of Internet literacy among college in ideological and also in the political teaching under the application of virtual reality technology. Internet literacy is defined as the ability to search and utilise information from the Internet. It includes the person's ability to communicate with people, the ability to protect their own privacy, and stay away from harmful and malicious content on the Internet. The basic computer skills, along with the ability to assess social media and search engines, the knowledge to handle Microsoft Office tools, send and receive emails, search for answers online, ask questions in forums, enrol in educational courses, etc., form the basis of Internet literacy. Ideological and political education is vital educational courses that need to be upgraded with the latest technological growth. The main idea of this proposed system is to cultivate Internet literacy among ideological and political education students by using VI technology. The model is found to deliver great results under the application of virtual reality technology. The proposed model implements a Back-Propagation Network Algorithm for the cultivation of Internet literacy among college students.


Novel approach to curatives of Mibyou (presymptomatic diseases).
The traditional Oriental medicine and health supplement have been empirically practiced but most of them have not come through objective examination to prove their efficacy. From pharmacological aspect, we have been investigating the medical benefits of traditional Oriental medicines and health supplements as curatives and their varied actions and mechanisms. The study on airway inflammation has shown that even a Kampo preparation, Bakumondo-to, has anti-inflammatory, anti-allergic, immunomodulatory, secretory-modulating and metabolic regulatory actions. The base of all its actions is founded on the restoration of normal molecular and cellular functions through DNA transcriptional regulation. In other previous studies, we showed that a health supplement, royal jelly (RJ) has weak estrogenic activity. RJ competes with 17β-estradiol for binding to the human estrogen receptors α and β, though it is much weaker than diethylstilbestrol in binding affinity. Treatment of MCF-7 cells with RJ enhances proliferation, and concomitant treatment with tamoxifen blocked this effect. A reporter gene assay showed that RJ enhanced transcription of the luciferase gene through the estrogen-responsive element in MCF-7 cells. Furthermore, subcutaneous injection of RJ restored the expression of vascular endothelial growth factor gene in the uteri of ovariectomized rats. We suggest that the diverse pharmacological functions of RJ can be ascribed, in part, to its estrogenic effects. We hypothesize that polyherbal medicines and health supplements, which have multiple actions, may be better than Western medicine of single component to treat various diseases including 'Mibyou' (presymptomatic disease). Our findings provide us with a new idea on the nature of disorder and disease-state development which involve complicated mechanisms and will contribute to novel principles to prevent diseases and establish new treatment. Adoption of means of translational research should provide objective background for efficacy and stimulate broader application and usage of traditional medicines and health supplements as curatives of Mibyou.


Successful management of descending necrotizing mediastinitis.
Descending necrotizing mediastinitis is a critical infection and the mortality rate remains high. Early aggressive surgical drainage and antibiotic therapy are essential for treatment. We evaluated the efficiency of transthoracic drainage using a minimally invasive technique in 11 cases of descending necrotizing mediastinitis between May 2002 and March 2008. We performed a right-side minithoracotomy with thoracoscopic assistance, and the mediastinum was thoroughly drained. The length of hospitalization ranged from 30 to 117 days. The postoperative course was good in all patients, and the outcome was favorable. All patients were discharged without major complications. We recommend employing a minithoracotomy with thoracoscopic assistance for aggressive treatment of descending necrotizing mediastinitis.


[A controversial problem: Oddi sphincterotomy in cholangitis].
The classical treatment of angiocholitis consists in desobstruction of the hepatic choledocus duct followed by external biliary drainage. However, this technique is unsuccessful in 66% of the cases, and this leads to difficult surgical reinterventions. In our casuistics are included 196 suppurated angiocholitis of various etiologies : lithiasis, hidatic cyst, post-hidatic angiocholitis, pure oddian angiocholitis etc. The Oddian component is present in a remarkable high number of cases (66%) and this is the reason why neglecting sphincterotomy may be followed by unfavourable results. In the paper the authors present their viewpoint, and the results of 128 interventions on the Oddi sphincter in patients with angiocholitis.


A N-terminal truncated intracellular isoform of matrix metalloproteinase-2 impairs contractility of mouse myocardium.
The full-length isoform of matrixmetalloproteinase-2 (FL-MMP-2) plays a role in turnover of the cardiac extracellular matrix. FL-MMP-2 is also present intracellularly in association with sarcomeres and, in the setting of oxidative stress, cleaves myofilament proteins with resultant impaired contractility. Recently, a novel N-terminal truncated MMP-2 isoform (NTT-MMP-2) generated during oxidative stress was identified and shown to induce severe systolic failure; however, the injury mechanisms remained unclear. In this study, cardiac-specific NTT-MMP-2 transgenic mice were used to determine the physiological effects of NTT-MMP-2 on: force development of intact myocardium; the function of cardiac myofilaments in demembranated myocardium; and on intracellular Ca(2+) transients in isolated myocytes. We related the contractile defects arising from NTT-MMP-2 expression to the known intracellular locations of NTT-MMP-2 determined using immunohistochemistry. Comparison was made with the pathophysiology arising from cardiac-specific FL-MMP-2 transgenic mice. Consistent with previous studies, FL-MMP-2 was localized to myofilaments, while NTT-MMP-2 was concentrated within subsarcolemmal mitochondria and to sites in register with the Z-line. NTT-MMP-2 expression caused a 50% reduction of force development by intact myocardium. However, NTT-MMP-2 expression did not reduce myofilament force development, consistent with the lack of NTT-MMP-2 localization to myofilaments. NTT-MMP-2 expression caused a 50% reduction in the amplitude of Ca(2+) transients, indicating impaired activation. Unlike FL-MMP-2, NTT-MMP-2 does not mediate myofilament damage. Instead, NTT-MMP-2 causes impaired myocyte activation, which may involve effects due to localization in mitochondria and/or to transverse tubules affecting Ca(2+) transients. Thus, FL-MMP-2 and NTT-MMP-2 have discrete intracellular locations and mediate different intracellular damage to cardiac myocytes.


Out-of-pocket costs attributable to dementia: A longitudinal analysis.
Alzheimer's disease and related dementias (ADRD) affect 5.7 million Americans, and are expensive despite the lack of a cure or even treatments effective in managing the disease. The literature thus far has tended to focus on the costs to Medicare, even though one of the main characteristics of ADRD (the loss of independence and ability to care for oneself) incurs costs not covered by Medicare. In this paper, we use survey data for 2002-2016 from the Health and Retirement Study to estimate the out-of-pocket costs of ADRD for the patient and their family through the first 8 years after the onset of symptoms, as defined by a standardized 27-point scale of cognitive ability. A two-part model developed by Basu and Manning (2010) allows us to separate the costs attributable to ADRD into two components, one driven by differences in longevity and one driven by differences in utilization. We identified a cohort of 3619 incident dementia cases, 38.9% were male, and 66.9% were non-Hispanic White. Dementia onset was 77.7 years of age, on average. OOP costs attributable to dementia are $8751 over the first 8 years after the onset. These incremental costs are driven by nursing home expenditures, which are largely uninsured in the US. OOP spending is highest for whites and women. The financial burden of ADRD is significant, and largely attributable to the lack of wide-spread long-term care insurance.


A proof of principle study of atomoxetine for the prevention of vasovagal syncope: the Prevention of Syncope Trial VI.
There are few effective therapies for vasovagal syncope (VVS). Pharmacological norepinephrine transporter (NET) inhibition increases sympathetic tone and decreases tilt-induced syncope in healthy subjects. Atomoxetine is a potent and highly selective NET inhibitor. We tested the hypothesis that atomoxetine prevents tilt-induced syncope. Vasovagal syncope patients were given two doses of study drug [randomized to atomoxetine 40 mg (n = 27) or matched placebo (n = 29)] 12 h apart, followed by a 60-min drug-free head-up tilt table test. Beat-to-beat heart rate (HR), blood pressure (BP), and cardiac haemodynamics were recorded using non-invasive techniques and stroke volume modelling. Patients were 35 ± 14 years (73% female) with medians of 12 lifetime and 3 prior year faints. Fewer subjects fainted with atomoxetine than with placebo [10/29 vs. 19/27; P = 0.003; risk ratio 0.49 (confidence interval 0.28-0.86)], but equal numbers of patients developed presyncope or syncope (23/29 vs. 21/27). Of patients who developed only presyncope, 87% (13/15) had received atomoxetine. Patients with syncope had lower nadir mean arterial pressure than subjects with only presyncope (39 ± 18 vs. 69 ± 18 mmHg, P < 0.0001), and this was due to lower trough HRs in subjects with syncope (67 ± 30 vs. 103 ± 32 b.p.m., P = 0.006) and insignificantly lower cardiac index (2.20 ± 1.36 vs. 2.84 ± 1.05 L/min/m2, P = 0.075). There were no significant differences in stroke volume index (32 ± 6 vs. 35 ± 5 mL/m2, P = 0.29) or systemic vascular resistance index (2156 ± 602 vs. 1790 ± 793 dynes*s/cm5*m2, P = 0.72). Norepinephrine transporter inhibition significantly decreased the risk of tilt-induced syncope in VVS subjects, mainly by blunting reflex bradycardia, thereby preventing final falls in cardiac index and BP.


In vitro characterization of a murine recipient anti-donor effector cell responsible for the development of chronic graft-versus-host disease.
Injection of parental spleen cells into unirradiated F1 hybrid recipients is frequently used for the induction of murine graft-vs-host disease (GVHD). Injection of C57BL/6 spleen cells into B6D2F1 recipients results in the acute form of GVHD whereas injection of DBA/2J cells into the same recipients results in a chronic form of GVHD. In vivo studies have suggested that injection of DBA/2J cells into B6D2F1 recipients results in the chronic form of GVHD instead of acute GVHD because of recipient B6D2F1 effector cells that inhibit DBA/2J CD8+ T cell function. The present report describes the development of an in vitro assay that measures the activity of these B6D2F1 effector cells. The results obtained using this assay indicate that these B6D2F1 effector cells are found primarily in the LN, need to be activated in order to function, are inhibited by anti-CD8 antibodies, and mediate their function as a result of DBA/2J cells binding to Ag expressed on their cell surface.


PTX3 Regulation of Inflammation, Hemostatic Response, Tissue Repair, and Resolution of Fibrosis Favors a Role in Limiting Idiopathic Pulmonary Fibrosis.
PTX3 is a soluble pattern recognition molecule (PRM) belonging to the humoral innate immune system, rapidly produced at inflammatory sites by phagocytes and stromal cells in response to infection or tissue injury. PTX3 interacts with microbial moieties and selected pathogens, with molecules of the complement and hemostatic systems, and with extracellular matrix (ECM) components. In wound sites, PTX3 interacts with fibrin and plasminogen and favors a timely removal of fibrin-rich ECM for an efficient tissue repair. Idiopathic Pulmonary Fibrosis (IPF) is a chronic and progressive interstitial lung disease of unknown origin, associated with excessive ECM deposition affecting tissue architecture, with irreversible loss of lung function and impact on the patient's life quality. Maccarinelli et al. recently demonstrated a protective role of PTX3 using the bleomycin (BLM)-induced experimental model of lung fibrosis, in line with the reported role of PTX3 in tissue repair. However, the mechanisms and therapeutic potential of PTX3 in IPF remained to be investigated. Herein, we provide new insights on the possible role of PTX3 in the development of IPF and BLM-induced lung fibrosis. In mice, PTX3-deficiency was associated with worsening of the disease and with impaired fibrin removal and subsequently increased collagen deposition. In IPF patients, microarray data indicated a down-regulation of PTX3 expression, thus suggesting a potential rational underlying the development of disease. Therefore, we provide new insights for considering PTX3 as a possible target molecule underlying therapeutic intervention in IPF.


Increase of doxorubicin sensitivity for folate receptor positive cells when given as the prodrug N-(phenylacetyl) doxorubicin in combination with folate-conjugated PGA.
Folate receptor (FR) has been proposed as a promising target for tumor drug targeting. The aim of this study was to increase the chemo-sensitivity of FR-positive cells to doxorubicin by folate-directed enzyme prodrug therapy (FDEPT). Folate conjugated penicillin-G amidase was prepared and its ability to hydrolyze N-(phenylacetyl) doxorubicin was measured by HPLC. Fluorescence and confocal image analysis revealed that Folate-PGA can be specifically delivered into FR-positive HeLa and SKOV3 tumor cells. In vitro cytotoxity assays, IC50 was reduced with N-(phenylacetyl) doxorubicin versus doxorubicin for HeLa (3.1-fold reduction; p<0.001) and SKOV3 (3.3-fold reduction; p<0.001) when Folate-PGA was specifically bound to the cells. Complete activation was confirmed in HeLa and SKOV3 cells pretreated with free folic acid (1 mM), where the combination of N-(phenylacetyl) doxorubicin with Folate-PGA did not show any significant cell toxicity to the IC50 of doxorubicin. Pharmacokinetic clearance and biodistribution studies in vivo showed that 125I-Folate-PGA was cleared from blood within 24 h and had significantly higher tumor uptake compared to 125I-PGA (p<0.05). These results demonstrate that the FDEPT approach may be a potential promising strategy to improve chemotherapy-resistant cancers therapeutic ratio and warranted future studies.


Does the subspecialty of the surgeon performing primary colonic resection influence the outcome of patients with hepatic metastases referred for resection?
To compare resection rates and outcome of patients subsequently referred with hepatic metastases whose initial colon cancers were resected by surgeons with different specialty interests. Variation in practice among noncolorectal specialist surgeons has led to recommendations that colorectal cancers should be treated by surgeons trained in colorectal surgery or surgical oncology. The resectability of metastases, the frequency and pattern of recurrence after resection, and the length of survival were compared in patients referred to a single center for resection of colorectal hepatic metastases. The patients were divided into those whose colorectal resection had been performed by general surgeons (GS) with other subspecialty interests (n = 108) or by colorectal specialists (CS; n = 122). RESULTS No differences were observed with respect to age, sex, tumor stage, site of primary tumor, or frequency of synchronous metastases. Comparing the GS group with the CS group, resectable disease was identified in 26% versus 66%, with tumor recurrence after a median follow-up of 19 months in 75% versus 44%, respectively. Recurrences involving bowel or lymph nodes accounted for 55% versus 24% of all recurrences, with respective median survivals of 14 months versus 26 months. Fewer patients referred by general surgeons had resectable liver disease. After surgery, recurrent tumor was more likely to develop in the GS group; their overall outcome was worse than that of the CS group. This observation is partly explained by a lower local recurrence rate in the CS group.


Recanalization-Like Neovascularization of Placental Intervillous Hematoma: First Two Reports.
Placental intervillous hematomas have not previously been reported to undergo any sort of change, maturation, or healing. In this article, we present the first 2 case reports of recanalization-like neovascularization within placental hematomas: a 0.15 cm focus in an intervillous fibrin thrombus and a 0.2 cm focus in a subchorionic hematoma. Increased recognition and further studies are needed to gain a better understanding of this seemingly rare phenomenon and the factors that govern the lack of typical organization in placental hematomas. This might lead to a deeper knowledge of the repair process in general and shed light on how to control it in diseases caused by excessive repair.


Ultrasound monitoring of gestosis polycentric study.
In polycentric research we studied 62 selected cases of gestosis to evaluate which symptom is greatly correlated with the deficit of fetal growth. According to us, the earlier the syndrome appearance the clearer the deficit of fetal growth.


Spontaneous rupture of renal angiomyolipoma.
We report a case of renal angiomyolipoma with retroperitoneal hemorrhage treated by enucleation in a 47 year-old male. The mass in the anterior side of the left kidney, revealed by sonography and CT, was diagnosed as angiomyolipoma with a retroperitoneal hematoma caused by its spontaneous rupture. Removal of hematoma and enucleation of the tumor were performed after the diagnosis. Diagnosis and treatment of ruptured renal angiomyolipoma are discussed.


Therapeutic effect of gefitinib on patients with advanced EGFR-mutation NSCLC.
This study aims to study the role of gefitinib on patients with advanced EGFR-mutation NSCLC (Non-Small Cell Lung Cancer). Totally 115 patients with advanced EGFR-mutation NSCLC treated in our hospital were enrolled as research objects. They were randomly divided into control group (n=57) applied with cisplatin ± pemetrexed and experimental group (n=58) subject to gefitinib± cisplatin ± pemetrexed, both groups were applied with treatment for 4 cycles. Clinical efficacy: The disease control rate (DCR) was 72.41% in the experimental group, which was higher than that of the control group (54.39%, p<0.05); Serum CEA, CYFRA21-1, MMP-9 levels: after 2 and 4 cycles of treatment, serum CEA, CYFRA21-1, and MMP-9 levels were lower in the experimental group (p<0.05); Immune function: after 2 and 4 cycles of treatment, Th1 cells and Th1/Th2 cell levels were higher in the experimental group, while Th2 cell level was higher in the control group (p<0.05); Angiogenesis related indicators: the levels of VEGF, HIF-1α and sCD105 were lower in the experimental group after 2 and 4 cycles of treatment (p<0.05); (5) Adverse reactions: After 2 and 4 cycles of treatment, the levels of VEGF, HIF-1α, and sCD105 were lower in the experimental group (p<0.05). The application of gefitinib in patients with advanced EGFR-mutation NSCLC can help down-regulate CEA, CYFRA21-1, and MMP-9 levels, inhibit angiopoiesis, enhance immune function, and increase disease control rate.


Effects of mifepristone in vivo on decidual prostaglandin synthesis and metabolism.
Mifepristone is an effective abortifacient in combination with an exogenous prostaglandin but its mechanism of action is unknown. Mifepristone stimulates prostaglandin production from decidua in tissue culture. To determine whether this effect also operates in vivo, we treated women with mifepristone 24, 36 and 48 hours prior to surgical termination. Decidua was removed at operation and the ability of the tissue to generate prostaglandin in culture subsequently assessed. Pretreatment with mifepristone 36 hours prior to termination of pregnancy resulted in an increased production of PGF2 alpha in tissue culture (p less than 0.01). A significant decrease in PGFM production was seen 24 hours after pretreatment with mifepristone in vivo (p less than 0.01). These results suggest that the increased uterine activity observed after administration of mifepristone may be due to stimulation of endogenous prostaglandin production and inhibition of prostaglandin metabolism.


Integrated Acoustic Chip for Culturing 3D Cell Arrays.
Three-dimensional (3D) cell arrays provide an in vitro platform for clinical drug screening, but the bulky culture devices limit their application scenarios. Here, we demonstrate an integrated portable device that can realize contact-free construction of 3D cell spheroids. The interaction between the ultrasound generated by the portable device and the capillary results in periodic pressure nodes or anti-nodes, which lead to form a 3D cell array for cell culture. Such a 3D cell array pattern can be constructed in seconds and requires only 1 μL of cell samples. We further assessed the spheroids formed by the portable device and the impact of the acoustic field on spheroids and demonstrated the drug screening with assembled spheroids. More importantly, the integrated acoustic device can be further integrated with other components for more complex cell culture and all-round analysis. This portable and effective integrated device provides a new avenue for clinical biomedicine.


Antisense RNA inhibition of phosphoprotein p18 expression abrogates the transformed phenotype of leukemic cells.
Phosphoprotein p18 was identified originally on the basis of its very high level of expression in leukemic cells of different lineages. Changes in the level of p18 accumulation and phosphorylation associated with induction of differentiation of leukemic cells suggested a potential role for this phosphoprotein in cellular proliferation and differentiation and possibly in malignant transformation. Recent studies have demonstrated that p18 plays an important role in cell cycle progression by serving as a substrate for p34(cdc2) kinase. These studies showed that inhibition of p18 expression in leukemic cells results in growth retardation and accumulation of cells in G(2)-M. In this study, we explore the potential role of p18 in cellular transformation by investigating the effects of inhibition of p18 expression on the malignant phenotype of K562 erythroleukemia cells. These studies show that antisense inhibition of p18 expression in leukemic cells results in growth arrest at a lower saturation density, loss of serum independence, and loss of anchorage-independent growth in vitro. In addition, inhibition of p18 expression results in a marked inhibition of tumorigenicity of leukemic cells in vivo in the severe combined immune deficiency mouse model. These studies demonstrate that the high level of p18 expression in leukemic cells is necessary for the maintenance of the transformed phenotype and suggest p18 as a potential target for antileukemic interventions.


A yeast one-hybrid system to screen for methylated DNA-binding proteins.
We had previously exploited a method for targeted DNA methylation in budding yeast to succeed in one-hybrid detection of methylation-dependent DNA-protein interactions. Based on this finding, we developed a yeast one-hybrid system to screen cDNA libraries for clones encoding methylated DNA-binding proteins. Concurrent use of two independent bait sequences in the same cell, or dual-bait system, effectively reduced false positive clones, which were derived from methylation-insensitive sequence-specific DNA-binding proteins. We applied the dual-bait system to screen cDNA libraries and demonstrated efficient isolation of clones for methylated DNA-binding proteins. This system would serve as a unique research tool for epigenetics.


Rapid accelerations of Antarctic Peninsula outlet glaciers driven by surface melt.
Atmospheric warming is increasing surface melting across the Antarctic Peninsula, with unknown impacts upon glacier dynamics at the ice-bed interface. Using high-resolution satellite-derived ice velocity data, optical satellite imagery and regional climate modelling, we show that drainage of surface meltwater to the bed of outlet glaciers on the Antarctic Peninsula occurs and triggers rapid ice flow accelerations (up to 100% greater than the annual mean). This provides a mechanism for this sector of the Antarctic Ice Sheet to respond rapidly to atmospheric warming. We infer that delivery of water to the bed transiently increases basal water pressure, enhancing basal motion, but efficient evacuation subsequently reduces water pressure causing ice deceleration. Currently, melt events are sporadic, so efficient subglacial drainage cannot be maintained, resulting in multiple short-lived (<6 day) ice flow perturbations. Future increases in meltwater could induce a shift to a glacier dynamic regime characterised by seasonal-scale hydrologically-driven ice flow variations.


Understanding stress through the genome.
Stress-induced glucocorticoid hormones support coping with and adaptation to different stressors. They act to modulate gene expression in a tissue and stressor-specific manner through activation of corticosteroid receptors, which act as transcription factors. Here, a number of recent insights in gene regulation under the influence of glucocorticoids are discussed. Emphasis is put on distinct classes of target genes that may be defined, based on categorization of (combinations of) transcription factor binding sites in responsive genes. These categories depend on insights into different mechanisms of transcriptional regulation, such as transactivation vs transrepression, and high affinity vs low affinity hormone receptor response elements. It is argued that such classes, based on mechanistic understanding of transcription regulation, in combination with the availability of complete genomic sequences and expression data from different organs, may enhance our understanding of the way in which organisms deal with different forms of stress.


Evaluation of Isosorbide Mononitrate for Preinduction of Cervical Ripening: A Randomized Placebo-Controlled Trial.
To evaluate the safety and efficacy of Isosorbide mononitrate (IMN) as a cervical ripening agent prior to induction of labour in term pregnant women. A randomized placebo-controlled study was conducted on 100 term singleton pregnancies planned for induction of labour. The participants were randomly assigned to two groups. One group received 40 mg IMN and the other group received 40mg of placebo kept vaginally. The main outcome of this study was to evaluate the efficacy of IMN in cervical ripening based on the change in modified Bishop score and the effect on time duration between the drug insertion and delivery. Safety of isosorbide mononitrate was assessed by measuring variables related to maternal and neonatal outcomes. Baseline demographic characteristics were similar in both groups. The mean change in modified Bishop score after 2 doses of 40mg IMN was insignificant when compared to placebo. Though IMN shortened the time duration between the drug insertion to delivery when compared to placebo, it was statistically insignificant. The need for oxytocin and 2(nd) ripening agent was less in IMN group when compared to placebo group but statistically this also proved to be insignificant. It was noted that there was an increase in caesarean deliveries in IMN than in placebo group. IMN did not cause any significant change in maternal hemodynamics and adverse side effects. Though NICU admission and stay was less in IMN than in placebo group, it was statistically insignificant. Though IMN did not cause any maternal and neonatal adverse effects, it was found to be inefficient in comparison to placebo as a cervical ripening agent.


Elastographic imaging of strain distribution in the anterior cruciate ligament and at the ligament-bone insertions.
The anterior cruciate ligament (ACL) functions as a mechanical stabilizer in the tibiofemoral joint, and is the most commonly injured knee ligament. To improve the clinical outcome of tendon grafts used for ACL reconstructions, our long-term goal is to promote graft-bone integration via the regeneration of the native ligament-bone interface. An understanding of strain distribution at this interface is crucial for functional scaffold design and clinical evaluation. Experimental determination, however, has been difficult due to the small length scale of the insertion sites. This study utilizes ultrasound elastography to characterize the response of the ACL and ACL-bone interface under tension. Specifically, bovine tibiofemoral joints were mounted on a material testing system and loaded in tension while radiofrequency (RF) data were acquired at 5 MHz. Axial strain elastograms between RF frames and a reference frame were generated using crosscorrelation and recorrelation techniques. Elastographic analyses revealed that when the joint was loaded in tension, complex strains with both compressive and tensile components occurred at the tibial insertion, with higher strains found at the insertion sites. In addition, the displacement was greatest at the ACL proper and decreased in value gradually from ligament to bone, likely a reflection of the matrix organization at the ligament-bone interface. Our results indicate that elastography is a novel method that can be readily used to characterize the mechanical properties of the ACL and its insertions into bone.


Statistical optimization of a reversed-phase liquid chromatographic method for the determination of amiloride and methyclothiazide in tablets.
A quantitative high-performance liquid chromatographic method in which amiloride is separated from methyclothiazide on a C18 column with detection at 286 mm was developed with the aid of the 'window diagram' technique of Laub and Purnell. The effect of simultaneously varying the pH and methanol to water ratio in the mobile phase were studied to optimize the separation. The method was applied to the quantitative analysis of Lometazid tablets. The powdered tablets were extracted with methanol, containing phenacetin as the internal standard, and assayed by comparison of peak heights after liquid chromatography.


[The validity of the certification of natimortality: the experience of a local study].
Although several study confirmed the inaccuracy of information in death certificates, very few investigations were performed to assess the validity of stillbirth certificate reporting. The aim of the present study was to evaluate the extent to which the clinical diagnosis of stillbirth cause reported in certificates can be considered sensitive and specific. Eighty-five consecutive stillbirths were independently classified by two neonatologists with certificate information, using the new Wigglesworth classification, and the reliability of the classification process was evaluated. Afterwards we compared the classes made with certificate causes and the ones made with clinical-autoptic data (the "gold standard") and we estimated sensitivity and specificity of certificate cause of stillbirth. The reliability of the classification process was very high. Values of sensitivity were considered unacceptable, mainly in the field of congenital malformations, intra-partum asphyxia and other specific causes. By contrast, specificity was found to be satisfactory. The accuracy of clinical stillbirth diagnosis is not sufficient and good description needs the contribute of post-mortem necropsy.


Indication-related dosing for magnetic resonance contrast media.
This presentation reviews the issue of contrast media dosing and imaging protocols for the optimal MR imaging detection and characterization of pathology. The cumulative clinical experience gained in performing contrast-enhanced MR examinations with gadolinium chelates indicates that a dose of 0.1 mmol/kg body weight provides safe and effective enhancement of most CNS pathology. Doses lower than 0.1 mmol/kg have been shown to be inadequate for delineating all but selected types of CNS pathology, such as masses with a high lesion to background ratio on post-contrast images (acoustic neuromas) or lesions located in areas in which the normal tissue very rapidly takes up contrast agent (e. g. microadenomas in the pituitary gland). Recent clinical studies have suggested a role for high dose gadolinium administration (up to 0.3 mmol/kg) for the optimal detection and delineation of cerebral metastases or other small or poorly enhancing lesions. Differences in the histopathologic characteristics (capillary permeability, vascularity, location, size) of specific diseased tissues may require varying doses or even a different contrast agent to be used for optimal imaging results. As new MR contrast agents and new scanning techniques are introduced, the specific diagnostic question posed will likely determine the choice of pulse sequence, contrast agent and dose used.


CE: Improving Outcomes for Patients with Chronic Kidney Disease: Part 2.
: Coping with chronic kidney disease (CKD) is challenging for many people, since symptoms often don't appear until the disease is advanced and the patient is close to requiring dialysis. This two-part article aims to provide nurses with the basic information necessary to assess and manage patients with CKD. Part 1, which appeared last month, offered an overview of the disease, described identification and etiology, and discussed ways to slow disease progression. Part 2 addresses disease complications and treatment for kidney failure.