GM1 ganglioside: another nuclear lipid that modulates nuclear calcium. GM1 potentiates the nuclear sodium-calcium exchanger.
The nuclear envelope (NE) enclosing the cell nucleus, although morphologically and chemically distinct from the plasma membrane, has certain features in common with the latter including the presence of GM1 as an important modulatory molecule. This ganglioside influences Ca(2+) flux across both membranes, but by quite different mechanisms. GM1 in the NE contributes to regulation of nuclear Ca(2+) through potentiation of a Na(+)/Ca(2+) exchanger in the inner nuclear membrane, whereas in the cell membrane, it regulates cytosolic Ca(2+) through modulation of a nonvoltage-gated Ca(2+) channel. Studies with neuroblastoma cells suggest GM1 concentration becomes elevated in the NE with onset of axonogenesis. However, the nuclear GM1/exchanger complex is not limited to neuronal cells but also occurs in NE of astrocytes, C6 cells, and certain non-neural cells. Immunoprecipitation and immunoblot experiments have shown high affinity association of the nuclear Na(+)/Ca(2+) exchanger with GM1, in contrast to Na(+)/Ca(2+) exchangers of the plasma membrane, which bind GM1 less avidly or not at all. This is believed to be due to different isoforms of the exchanger and a difference in topology of GM1 relative to the large inner loop of the exchanger in the 2 membranes. Cultured neurons from mice genetically engineered to lack GM1 suffered Ca(2+) dysregulation as seen in their high vulnerability to Ca(2+)-induced apoptosis. They were rescued by GM1 and more effectively by LIGA20, a membrane-permeant derivative of GM1. The mutant animals were highly susceptible to kainate-induced seizures, which are also a reflection of Ca(2+) dysregulation. The seizures were effectively attenuated by LIGA20 in parallel with the ability of this agent to enter brain cells, insert into the NE, and potentiate Na(+)/Ca(2+) exchange activity in the nucleus. The Na(+)/Ca(2+) exchanger of the NE, in association with nuclear GM1, is thus seen contributing to independent regulation of Ca(2+) by the nucleus in a manner that provides cytoprotection against Ca(2+)-induced apoptosis.


[A preliminary study on the clinical characteristics of Parkinson's disease patients with restless legs syndrome].
Objective: To study the clinical characteristics of Parkinson's disease (PD) patients with restless legs syndrome (RLS). Methods: Ninety-nine PD patients and eighty-nine control group were included into this study and assessed for RLS by the question 6 of the non-motor symptoms questionnaire (NMSquest). The PD patients were divided into the RLS group and non RLS group, according to their answers to the NMSquest.The severity of motor symptoms, anxiety, depression and quality of life were evaluated according Unified Parkinson Disease Rating Scale (UPDRS), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), Parkinson' s Disease Quality Of Life Questionnaire(PDQ-39), respectively. Results: (1)18.2%(18/81)of the PD patients experienced RLS, the incidence was significantly higher than the general population (P<0.001). (2) The RLS patients were more often women (66.7% vs 33.3%, P=0.033 ). (3) The UPDRS-Ⅱ score(20±7, P=0.008), UPDRS-Ⅲ score(43±14, P=0.015), BDI score(23±13, P=0.002), BAI score(18±8, P=0.012), PDQ-39 score(75±26, P=0.000)in RLS group were significantly higher compared with non RLS group. (4) RLS showed no association with the course of the disease, the age, the PD onset age and levodopa dose equivalents. Conclusions: RLS more likely appears in PD patients, especially in women. The PD patients with RLS commonly suffer from serious motor symptom, low quality of life, anxiety and depression.


[Dr Leonor Michaelis and early days of Hokkaido University School of Medicine; episodes among three medical researchers in the roaring twenties].
Little has been known about the personal history of Dr. Takaichi Mohri (Nakashima), the first professor of department of hygiene at Hokkaido University School of Medicine. We, therefore, have been inquiring academic backgrounds of Dr. Mohri for two decades. These inquiries show interesting episodes between Dr. Leonor Michaelis, one of the biggest names in enzymologists, and early days of this Medical School. In this article, we describe that at least two professors, Drs. Takaichi Mohri and Kaoru Ohguro, were in good acquaintances with Dr. Michaelis as follows; 1) the latter half of 1921, Dr. Ohguro visited a laboratory of Dr. Michaelis in Berlin, 2) from November 1922 to June 1923, Dr. Michaelis in Nagoya collaborated with Dr. Mohri in Sapporo, 3) Dr. Michaelis in Nagoya visited Dr. Ohguro's house and office in Sapporo at March 1925, and 4) at the same occasion, Dr. Michaelis made his lecture on biochemistry in Hokkaido University School of Medicine. Since Drs. Ohguro and Mohri were classmates of the University of Tokyo Faculty of Medicine, Dr. Ohguro could introduce Dr. Michaelis to Dr. Mohri who used to be a graduate student in department of biochemistry. As a result of relationships, Drs. Michaelis and Mohri published a paper entitled "Eine weitere Methode zur Bestimmung des isoelektrischen Punktes von Eiweisskoerpern und ihre Anwendung auf die Serumalbumine verschiedener Tiere" in Biochemische Zeitschrift, which was a part of Dr. Mohri's Ph.D. thesis.


Patients' experiences of living with oesophageal cancer.
The aim of this study is to describe patients' experiences of living with oesophageal cancer and how they seek information. Oesophageal cancer is a devastating disease with poor prognosis. Nursing care for individuals with oesophageal cancer requires increased knowledge of how they experience illness and how it affects them. Data were collected by semi-structured, qualitative interviews with 13 participants. Content analysis was used to analyse data. Four themes were identified: (i) Experiences of becoming a patient diagnosed with oesophageal cancer is distinguished by the participants' experiences of vague symptoms, of receiving the diagnosis and of existential concerns evoked by the illness. (ii) Experiences of undergoing investigations and treatment consist of the participants' experiences of extreme tiredness in relation to investigations and treatment. (iii) Experiences of intrusions in daily life is conceptualized by the participants' experiences of how the illness influenced their daily life. (iv) Managing a life-threatening illness consists of a variety of strategies, which the participants employed to manage their life-threatening illness. The participants were unprepared of receiving a diagnosis of oesophageal cancer. Dysphagia, fatigue and uncertainty influenced the participants' everyday life. To manage the illness one of their strategies was seeking for information. The physicians were considered the main source of information, but family as well as friends with medical knowledge were also acknowledged as valuable sources. Understanding patients' experiences of living with oesophageal cancer is important to improve nursing care. When caring for these patients, focus ought to be on the whole family. In nursing care, it is important to be aware of the effects of dysphagia and fatigue. Health-care professionals ought to organize meetings with fellow patients and recommend literature and websites that provide patients with high quality information.


[A nutritional investigation of homeless patients with tuberculosis].
A retrospective case-control study was performed with TB patients who were admitted to our hospital over the two years from Jan. 1997 to Dec. 1998 and healthy men who underwent a health screening in April 2000 in the same hospital. Thirty-two non-homeless TB patients (the first control group) and 32 healthy men (the second control group) were matched with 32 homeless TB patients according to age. All 3 groups were male. Total protein, albumin, cholesterol, cholinesterase, hemoglobin level and lymphocyte count on admission were significantly lower in the homeless patients than in the non-homeless patients and healthy men. Albumin, cholesterol, cholinesterase, hemoglobin level, white blood cell count and lymphocyte count on admission were significantly lower in non-homeless patients than healthy men. Height, weight and body mass index were significantly lower in the homeless patients than in the healthy men. However, there were no significant differences in these body characteristics between the homeless and non-homeless patients. Twenty-five percent of homeless patients died during hospitalization, compared with 6.3 percent of non-homeless patients. Lymphocyte counts among homeless patients who died during hospitalization were significantly lower than among those who survived during hospitalization. Total protein, albumin, cholesterol, cholinesterase, hemoglobin level and weight were lower in patients who died than in those who survived, although the differences were statistically not significant.


The role of reactive nitrogen/oxygen intermediates in cytokine-induced trophoblast apoptosis.
Reactive oxygen and nitrogen intermediates (ROI, RNI), such as superoxide anion, nitric oxide (NO) and peroxynitrite, are present in villous trophoblasts and mediate TNF-alpha-induced apoptosis in other cell types. We therefore proposed that ROI/RNI mediate cytokine-induced apoptosis of cultured villous cytotrophoblasts. Treatment of cultures of highly purified term cytotrophoblasts with TNF-alpha and IFN-gamma had no effect on NO synthase (NOS) protein expression measured by immunoblot analysis: iNOS was not expressed and eNOS expression was unaffected. NO production assessed by nitrite levels was below detection limits of the Griess reaction and the NOS inhibitors L-NAME and L-NMMA did not decrease cytokine-stimulated apoptosis. Trophoblasts produced ROI and expressed Cu/Zn superoxide dismutase (SOD) protein but neither was affected by cytokine treatment. ROI scavengers (exogenous SOD, ascorbic acid and butylated hydroxyanisole) also had no effect on cytokine-stimulated apoptosis. Nitrotyrosine immunoblot analysis indicated peroxynitrite production but again cytokines did not reproducibly alter expression patterns or band intensities. Exogenous peroxynitrite stimulated cytotrophoblast apoptosis but only at high levels (1000 microM). We conclude that, although present in cultured villous cytotrophoblasts, ROI/RNI are not induced by TNF-alpha and IFN-gamma and do not mediate cytokine-induced apoptosis.


A large bullet in the bladder.
All manner of foreign bodies have been extracted from the bladder. Introduction into the bladder may be through self-insertion, iatrogenic means or migration from adjacent organs. Extraction should be tailored according to the nature of the foreign body and should minimise bladder and urethral trauma. We report a case of a bullet injury to the bladder, which finally presented as a gross hematuria after remaining asymptomatic for four years. We present here an alternative to suprapubic cystostomy with a large bladder foreign body treated via a combined transurethral unroofing followed by removal using a grasper passed through a suprapubic laparoscopic port.


Coupled modes of the resonance box of the guitar.
Vibrations of the resonance box of the guitar have been studied by means of the modal analysis technique and the finite-element method. An expert craftsman constructed the guitar box with all the structures, internal and external, characteristic of a real instrument for the experimental measurements. The boundary conditions were chosen in order to clarify the soundboard-back interaction only via the internal air coupling. The numerical model allows one to study the influence of each component on the whole box, and the contribution of the modes of the components (wooden box and its parts, and air), to the coupled modes by calculating their participation factors. The coupled modes of the guitar box are discussed taking into account both the finite-element and modal analysis results.


Complementary NMR- and MS-based metabolomics approaches reveal the correlations of phytochemicals and biological activities in Phyllanthus acidus leaf extracts.
Proton nuclear magnetic resonance (1H NMR)- and ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS)-based analytical tools are frequently used in metabolomics studies. These complementary metabolomics platforms were applied to identify and quantify the metabolites in Phyllanthus acidus extracted with different ethanol concentrations. In total, 38 metabolites were tentatively identified by 1H NMR and 39 via UHPLC-MS, including 30 compounds are reported for the first time from this plant. The partial least square analysis (PLS) revealed the metabolites that contributed to α-glucosidase and nitric oxide (NO) inhibitory activities, including kaempferol, quercetin, myricetin, phyllanthusol A, phyllanthusol B, chlorogenic, catechin, cinnamic coumaric, caffeic, quinic, citric, ellagic and malic acids. This study shows the significance of combining 1H NMR- and UHPLC-MS-based metabolomics as the best strategies in identifying metabolites in P. acidus extracts and establishing an extract with potent antioxidant, anti-diabetic, and anti-inflammatory properties.


ProPAC's recommendations: refinements, not major changes.
The 21 recommendations in the Prospective Payment Assessment Commission's (ProPAC's) first report are consolidated under seven topics: update factor; hospital market basket; discretionary adjustment factor; area wage index; disproportionate-share hospitals; standardized amounts; and DRG classifications and weights. The key recommendations include: Increase rates by roughly 1 percent to 3 percent for fiscal year 1986 (this is inconsistent with the Reagan administration's proposal to freeze 1986 rates at the 1985 levels); Use a single market basket in fiscal year 1986 (although ProPAC also will examine the appropriateness of developing market baskets for different regions and classes of hospitals within regions); Revise the discretionary adjustment factor to reflect real changes in case mix; redefine labor market areas to reflect geographically based variations in wages paid to hospital workers (inner city, suburban, and rural); recalibrate DRG weights for 1986.


Measurement of the degree of polarization of the spectra from laser produced recombining Al plasmas.
Using a polarization-resolved UV-visible spectrometer, the degree of polarization of the spectra from laser produced Al plasmas was measured. The polarization resolution was achieved by using either a dichroic polarizer or a calcite crystal. The degree of polarization of Al III 4s(2)S(1/2)-4p(2)P(o)(3/2) transition at 569.66 nm was measured at different positions from a target surface. The degree of polarization was observed to be 2.1+/-0.13% at a distance of 220 microm from the target and decreased as the distance from the target increased, vanishing at a distance of about 1.3 mm from the target. To avoid the possible error due to the shot-to-shot variation of the line intensity, a calcite crystal was used to simultaneously observe the two polarization components, obtaining a similar result. The electron temperature of about 3 eV and the density of 2 x 10(17) cm(-3) measured spectroscopically indicates that the plasma was in the recombining phase. This is a report on the observation of the polarization of a transition in a laser-produced recombining Al plasma.


CTGF Is Expressed During Cystic Remodeling in the PKD/Mhm (cy/+) Rat Model for Autosomal-Dominant Polycystic Kidney Disease (ADPKD).
Connective tissue growth factor (CTGF, also named CCN2) plays an important role in the development of tubulointerstitial fibrosis, which most critically determines the progression to end-stage renal failure in autosomal-dominant polycystic kidney disease (ADPKD), the most common genetically caused renal disease. We determined CTGF expression in a well-characterized animal model of human ADPKD, the PKD/Mhm (cy/+) rat. Kidneys of 12 weeks old (cy/+) as well as (+/+) non-affected rats were analyzed for CTGF RNA and protein expression by RT-PCR, Northern and Western blot analyses, in situ hybridization, and IHC. Besides the established expression of CTGF in glomerular cells in kidneys of wild-type (+/+) animals, in (cy/+) rats, CTGF mRNA and protein were robustly expressed in interstitial, stellate-shaped cells, located in a scattered pattern underlying the cystic epithelium and in focal areas of advanced tubulointerstitial remodeling. Renal CTGF mRNA and protein expression levels were significantly higher in (cy/+) rats compared with their (+/+) littermates. Detection of CTGF expression in cells adjacent to cystic epithelium and in areas of marked fibrosis suggests a role in the local response to cyst development and indicates that CTGF may be a relevant factor contributing to tubulointerstitial fibrosis in polycystic kidney disease.


Modeling competitive reaction mechanisms of peroxynitrite oxidation of guanine.
5-Guanidino-4-nitroimidazole is a stable product from the peroxynitrite induced one-electron oxidation of guanine. Reaction mechanisms to form the 5-guanidino-4-nitroimidazole as well as 8-nitroguanine, through the combination of the guanine radical cation and nitrogen dioxide radical and through the combination of the deprotonated neutral guanine radical and nitrogen dioxide radical, have been investigated by the use of the B3LYP method of density functional theory. Our calculations suggest that the guanine radical cation mechanism is preferred over the neutral guanine radical mechanism and that a water molecule is involved in the reaction as a catalyst or as a reactant.


Copper-Mediated Radical-Induced Ring-Opening Relay Cascade Carboannulation Reaction of [60]Fullerene with Cyclobutanone Oxime Esters: Access to [60]Fullerene-Fused Cyclopentanes.
An unexpected copper-mediated radical-induced ring-opening relay cascade carboannulation reaction of [60]fullerene with cyclobutanone oxime esters is presented for the preparation of various Cl-/Br-incorporated [60]fullerene-fused cyclopentanes. The unique relay cascade transformation uses inexpensive copper salts as promoters and halogen sources and features simple redox-neutral conditions and a broad substrate scope, providing a practical access to a class of novel five-membered carbocycle-fused fullerenes.


Towards guest-zeolite interactions: an NMR spectroscopic approach.
Guest(metal)-zeolite interactions in a two component heterogeneous catalyst have been investigated by high-field and high-speed (27)Al MAS NMR, and two-dimensional (27)Al MQ MAS NMR experiments as well as ab initio DFT methods. It was established that strong interactions between guest and zeolite occur in a metal/zeolite system, with the metal anchored to the tetrahedral aluminum framework site through two oxygen bridges. It disturbs the tetrahedral environment of associated aluminum framework, changing AlO(4) geometry from near T(d) to C(2v); this enables us to resolve this species from the undisturbed aluminum framework species in high-field (27)Al MAS NMR and two-dimesional (27)Al MQ MAS NMR experiments.


A Recurrent Germline Mutation in the 5'UTR of the Androgen Receptor Causes Complete Androgen Insensitivity by Activating Aberrant uORF Translation.
A subset of patients with monogenic disorders lacks disease causing mutations in the protein coding region of the corresponding gene. Here we describe a recurrent germline mutation found in two unrelated patients with complete androgen insensitivity syndrome (CAIS) generating an upstream open reading frame (uORF) in the 5' untranslated region (5'-UTR) of the androgen receptor (AR) gene. We show in patient derived primary genital skin fibroblasts as well as in cell-based reporter assays that this mutation severely impacts AR function by reducing AR protein levels without affecting AR mRNA levels. Importantly, the newly generated uORF translates into a polypeptide and the expression level of this polypeptide inversely correlates with protein translation from the primary ORF of the AR thereby providing a model for AR-5'UTR mediated translational repression. Our findings not only add a hitherto unrecognized genetic cause to complete androgen insensitivity but also underline the importance of 5'UTR mutations affecting uORFs for the pathogenesis of monogenic disorders in general.


IL-10 is not required to prevent immune hyperactivity during memory responses to Toxoplasma gondii.
Primary infection of IL-10 knockout (KO) mice with the protozoan parasite Toxoplasma gondii leads to a CD4(+)-T-cell dependent shock-like reaction with high systemic levels of IL-12 and IFN-gamma, severe liver pathology and death of mice. In the present study, this immune-mediated pathology was prevented by treatment of IL-10 KO mice with the anti-parasitic drug sulfadiazine, allowing these mice to progress to the chronic phase of infection. To address the role of endogenous IL-10 in the regulation of secondary immune responses to T. gondii, IL-10 KO mice were infected with the avirulent Me49 strain of this parasite, treated with sulfadiazine for 2 weeks starting at day 3 p.i., and were rechallenged 6 weeks p.i. with RH, a highly virulent strain of T. gondii. In these studies, chronically infected IL-10 KO mice survived secondary infection with RH and controlled parasite load. Although serum levels of IL-12 and IFN-gamma were higher in IL-10 KO mice than in wild type (WT) mice 8 days after RH rechallenge, these levels were well controlled in the absence of endogenous IL-10, suggesting that IL-10 is not required to down-regulate cytokine production during the memory response. Antigen-specific ex vivo recall responses further revealed that splenocytes from chronically infected WT and IL-10 KO mice responded to parasite antigen with similar production of IL-12 and IFN-gamma, and there was also no significant difference in ex vivo production of these cytokines by splenocytes in response to parasite antigen 7 days after secondary infection with T. gondii. Furthermore, IL-10 KO mice immunized with the Ts-4 vaccine-strain of T. gondii were protected when rechallenged with the virulent RH strain. Together, these studies demonstrate that the inhibitory effect of IL-10, which is required to prevent immune-mediated pathology during primary infection, is not required to prevent immune hyperactivity during a secondary response to T. gondii, and a highly effective memory response is generated in the absence of endogenous IL-10.


Lactoferrin Ameliorates Dry Eye Disease Potentially through Enhancement of Short-Chain Fatty Acid Production by Gut Microbiota in Mice.
Lactoferrin is a glycoprotein found at high concentrations within exocrine secretions, including tears. Low levels of lactoferrin have been implicated in the loss of tear secretion and ageing. Furthermore, lactoferrin possesses a range of functionalities, including anti-inflammatory properties and the ability to modulate the gut microbiota. Expanding evidence demonstrates a crucial role of the gut microbiota in immune regulation and development. The specific composition of bacterial species of the gut has a profound influence on local and systemic inflammation, leading to a protective capacity against a number of inflammatory diseases, potentially by the induction of regulatory immune cells. In this study, we demonstrated that oral administration of lactoferrin maintains tear secretion in a restraint and desiccating stress induced mouse model of dry eye disease. Furthermore, we revealed that lactoferrin induces the reduction of inflammatory cytokines, modulates gut microbiota, and induces short-chain fatty acid production. Whereas, the antibiotic vancomycin abrogates the effects of lactoferrin on dry eye disease and significantly reduces short-chain fatty acid concentrations. Therefore, this protective effect of LF against a mice model of DED may be explained by our observations of an altered gut microbiota and an enhanced production of immunomodulatory short-chain fatty acids.


Cerebral arteriovenous malformations. Part 1: cellular and molecular biology.
The scientific understanding of the nature of arteriovenous malformations (AVMs) in the brain is evolving. It is clear from current work that AVMs can undergo a variety of phenomena, including growth, remodeling, and/or regression-and the responsible processes are both molecular and physiological. A review of these complex processes is critical to directing future therapeutic approaches. The authors performed a comprehensive review of the literature to evaluate current information regarding the genetics, pathophysiology, and behavior of AVMs. A comprehensive literature review was conducted using PubMed to reveal the molecular biology of AVMs as it relates to their complex growth and behavior patterns. Growth factors involved in AVMs include vascular endothelial growth factor, fibroblast growth factor, transforming growth factor beta, angiopoietins, fibronectin, laminin, integrin, and matrix metalloproteinases. Conclusions Understanding the complicated molecular milieu of developing AVMs is essential for defining their natural history. Growth factors, extracellular matrix proteins, and other molecular markers will be the key to unlocking novel targeted drug treatments for these brain malformations.


Co-cultivation of microbial sub-communities in microfluidic droplets facilitates high-resolution genomic dissection of microbial 'dark matter'.
While the 'unculturable' majority of the bacterial world is accessible with culture-independent tools, the inability to study these bacteria using culture-dependent approaches has severely limited our understanding of their ecological roles and interactions. To circumvent cultivation barriers, we utilize microfluidic droplets as localized, nanoliter-size bioreactors to co-cultivate subsets of microbial communities. This co-localization can support ecological interactions between a reduced number of encapsulated cells. We demonstrated the utility of this approach in the encapsulation and co-cultivation of droplet sub-communities from a fecal sample collected from a healthy human subject. With the whole genome amplification and metagenomic shotgun sequencing of co-cultivated sub-communities from 22 droplets, we observed that this approach provides accessibility to uncharacterized gut commensals for study. The recovery of metagenome-assembled genomes from one droplet sub-community demonstrated the capability to dissect the sub-communities with high-genomic resolution. In particular, genomic characterization of one novel member of the family Neisseriaceae revealed implications regarding its participation in fatty acid degradation and production of atherogenic intermediates in the human gut. The demonstrated genomic resolution and accessibility to the microbial 'dark matter' with this methodology can be applied to study the interactions of rare or previously uncultivated members of microbial communities.


Correlations of Equilibrium Properties and Electronic Structure of Pure Metals.
First principles calculations were carried out to study the equilibrium properties of metals, including the electrons at bonding critical point; ebcp; cohesive energy; Ecoh; bulk modulus; B; and, atomic volume; V. 44 pure metals, including the s valence (alkali), p valence (groups III to V), and d valence (transition) metals were selected. In the present work, the electronic structure parameter ebcp has been considered to be a bridge connecting with the equilibrium properties of metals, and relationships between ebcp and equilibrium properties (V; Ecoh; and B) are established. It is easy to estimate the equilibrium properties (Ecoh; V, and B) of pure metals through proposed formulas. The relationships that were derived in the present work might provide a method to study the intrinsic mechanisms of the equilibrium properties of alloys and to develop new alloys.


Inhibition of lipid peroxidation and superoxide generation by diterpenoids from Rosmarinus officinalis.
Four diterpenoids, carnosic acid (1), carnosol (2), rosmanol (3), and epirosmanol (4), were isolated as antioxidative agents from the leaves of Rosmarinus officinalis by bioassay-directed fractionation. These diterpenoids inhibited superoxide anion production in the xanthine/xanthine oxidase system. Mitochondrial and microsomal lipid peroxidation induced by NADH or NADPH oxidation were also completely inhibited by these diterpenes at the concentration of 3-30 microM. Furthermore, carnosic acid protected red cells against oxidative hemolysis. These phenolic diterpenes were shown to be effective to protect biological systems against oxidative stresses.


[Transmyocardial laser revascularization in stable and unstable angina pectoris].
Endstage coronary artery disease still remains a therapeutic challenge. An increasing number of patients is no longer amenable for direct revascularization by PTCA or coronary bypass surgery and does also no longer respond to maximum medical therapy. This fact has directed the interest again towards surgical techniques of indirect revascularization, which had been introduced by Beck and other surgeons more than 60 years ago. Among these attempts we can also find transmyocardial needle punctures, firstly performed by Sen in Bombay. In the early eighties it was Mirhoseini, who used a laser for creating these transmural channels, primarily in combination with coronary bypass surgery at the arrested heart and later on together with Crew as a sole therapy at the beating heart. The idea behind this transmyocardial laser revascularization (TMLR) was a "reptilization" of the human heart, which meant a direct blood supply from the ventricle into the ischemic myocardium. Whereas this theory has not proven to be true, as the surface area of these channels is not sufficient for the nutrition of the surrounding myocardial tissue by diffusion or convection, different models have been developed by anatomical, experimental and clinical studies, such as the connection between the laser channels and intramyocardial vessels or capillaries, analogous to ventriculo-coronary connections in human anatomy or pathology as for example those connections described in children with pulmonary atresia and intact ventricular septum or the Thebesian veins. Moreover the laser trauma may also simply contribute to the induction of neoangiogenesis. While the function of TMLR is still not clearly defined, clinical studies in the United States and also in other countries have proven the clinical efficacy in a cohort of severely diseased patients undergoing this procedure. Accordingly more than 2/3 of all patients after TMLR showed a significant improvement of more than 2 angina classes (CCS) as well as a decrease in medication and hospitalization. Moreover there was also a reduction of ischemic areas demonstrated by szintigraphy and, in one study from Houston, also by positron emission tomography. While the overall mortality in all those studies is still considerably high, a reduction could be achieved by a stricter selection of patients excluding especially those with a severely impaired left ventricular function. As demonstrated by preliminary data from the last phase III FDA-study, TMLR may even reduce long-term mortality compared to maximum medical therapy in a randomized group of patients. Our own experiences in 134 patients also confirmed a significant reduction of angina after TMLR alone (n = 67) or in combination with bypass surgery (n = 67) with the majority of patients being in angina class 1 and 2 (CCS) 6 months after surgery. All of these patients were in angina class 3 and 4 before surgery. Nuclear scans could demonstrate an improved perfusion in more than 40%. Further studies as well as other clinical and also experimental investigations have still to be awaited, before the definitive role of TMLR within the armamentarium against coronary artery disease can be determined. However, it is already a therapeutic option for those highly symptomatic patients, who cannot be offered a different treatment modality.


CT Imaging of Emergent Renal Conditions.
The kidneys are paired intra-abdominal organs which provide essential functions and maintain homeostasis throughout the human body. Numerous disease processes affect the kidneys and cause acute renal dysfunction or other potentially catastrophic complications. These conditions can be broadly categorized into obstructive, infectious, hemorrhagic, traumatic, and vascular diseases. Imaging plays a vital role in the work-up and diagnosis of acute and emergent renal conditions. Evaluation of emergent renal conditions with a focus on CT imaging is discussed.


The role of novel imaging in prostate cancer focal therapy: treatment and follow-up.
Multiparametric magnetic resonance imaging (mpMRI) has fundamentally changed how intraprostatic lesions are visualized, serving as a highly sensitive means for detecting clinically significant prostate cancer (csPCa) via image-targeted biopsy. However, limitations associated with mpMRI have led to the development of new imaging technologies with the goal of better characterizing intraprostatic disease burden to more accurately guide treatment planning and surveillance for prostate cancer focal therapy. Herein, we review several novel imaging modalities with an emphasis on clinical data reported within the past two years. 7T MRI, artificial intelligence applied to mpMRI, positron emission tomography combined with either computerized tomography or MRI, contrast-enhanced ultrasound, and micro-ultrasound are novel imaging modalities with the potential to further improve intraprostatic lesion localization for applications in focal therapy for prostate cancer. Many of these technologies have demonstrated equivalent or favorable diagnostic accuracy compared to contemporary mpMRI for identifying csPCa and some have even shown improved capabilities to define lesion borders, to provide volumetric estimates of lesions, and to assess the adequacy of focal ablation of planned treatment zones. Novel imaging modalities with capabilities to better characterize intraprostatic lesions have the potential to improve accuracy in treatment planning, real-time assessment of the ablation zone, and posttreatment surveillance; however, many of these technologies require further validation to determine their clinical utility.


[Cerebral infarction due to stenosis of the bilateral internal carotid artery in Turner's syndrome].
A 43-year-old woman was admitted into our hospital because of aphasia and right hemiparesis. Computed tomographic scan demonstrated border zone infarction in the anterior and middle cerebral artery. Magnetic resonance imaging scans showed the borderline area between the terminal branches of the lenticulostriate arteries and the perforating branches of the middle cerebral artery. Digital subtraction ICA angiogram showed severe narrowing of the distal portion of the right and left ICA. A pattern analysis of ambulatory blood pressure monitoring (ABPM) was carried out in this patient, and it was showed "dipper type". Laboratory data was elevated excretion of pituitary gonadotropines and low estrogen excretion. Chromosome analysis revealed the 45, X/46, XX. She was diagnosed with mosaic type of Turner's syndrome. The cerebrovascular abnormality might be due to congenital hypoplasia of arteries, and declining of blood pressure during sleep was possible significant factors in the pathogenesis of cerebral infarction in this patient.


Chondroprotective effects of CDK4/6 inhibition via enhanced ubiquitin-dependent degradation of JUN in synovial fibroblasts.
Targeting synovial fibroblasts (SF) using a cyclin-dependent kinase (CDK) 4/6 inhibitor (CDKI) could be a potent therapy for RA via inhibition of proliferation and MMP-3 production. This study was designed to elucidate the mechanism of chondroprotective effects on SFs by CDK 4/6 inhibition. CDK4/6 activity was inhibited using CDKI treatment or enhanced by adenoviral gene transduction. Chondroprotective effects were evaluated using a collagen-induced arthritis model (CIA). Gene and protein expression were evaluated with quantitative PCR, ELISA and Western blotting. The binding of nuclear extracts to DNA was assessed with an electrophoresis mobility shift assay. RNA-Seq was performed to identify gene sets affected by CDKI treatment. CDKI attenuated cartilage destruction and MMP-3 production in CIA. In RASFs, CDKI impaired the binding of AP-1 components to DNA and inhibited the production of MMP-1 and MMP-3, which contain the AP-1 binding sequence in their promoter. CDK4/6 protected JUN from proteasome-dependent degradation by inhibiting ubiquitination. The RNA-Seq analysis identified CDKI-sensitive inflammatory genes, which were associated with the pathway of RA-associated genes, cytokine-cytokine receptor interaction and IL-17 signalling. Notably, the AP-1 motif was enriched in these genes. The mechanism of chondroprotective effects by CDK4/6 inhibition was achieved by the attenuation of AP-1 transcriptional activity via the impaired stability of JUN. Because the pharmacologic inhibition of CDK4/6 has been established as tolerable in cancer treatment, it could also be beneficial in patients with RA due to its chondroprotective and anti-inflammatory effects.


Genitoperineal gangrene: experience in Singapore.
The experience with genitoperineal gangrene at the Department of Colorectal Surgery, Singapore General Hospital is documented. The results of 12 patients treated during the 5 year period between 1 January 1990 and 31 January 1995 were studied. There were 10 men and two women. The mean age of the patients was 55.2 (range 37-83) years. Perianal pain and swelling were the commonest presentation. However, three patients were admitted in a toxic state with mental confusion. The gangrene progressed from anorectal sepsis in six patients. Five of these patients had diabetes mellitus. Escherichia coli was the commonest organism cultured. Early diagnosis, immediate resuscitation, antibiotics and early aggressive surgery was our management policy. Applying these principles, all except two patients survived (mortality 17%). One had advanced malignancy and the other had extensive burn injuries. A high index of suspicion should be maintained in patients with diabetes and with anorectal sepsis. Should genitoperineal gangrene develop, aggressive surgery is often successful.


Biomechanical study of screws in the lateral masses: variables affecting pull-out resistance.
The purpose of this study was to investigate the effects of the design of the screw, the depth of insertion, the vertebral level, and the quality of the host bone on the pull-out resistance of screws used in the lateral masses. The study included twelve fresh cervical spines from human cadavera. Radiographs were made of each specimen to ensure the absence of defects, and then the cancellous-bone density of the vertebral bodies was measured at each level with quantitative computed tomography scanning. Six commercially available screws of various diameters and thread configurations (2.7, 3.2, 3.5, and 4.5-millimeter cortical-bone screws; a 3.5-millimeter cancellous-bone screw; and a 3.5-millimeter self-tapping screw) that are currently used for fixation of the cervical lateral masses were tested for axial load to failure. A twelve-by-twelve Latin square design was used to randomize the screws with regard to level (second through seventh cervical vertebrae), side (right and left), and depth of insertion (unicortical or bicortical purchase). Each screw was then subjected to uniaxial load to failure. The data were analyzed to determine if the diameter of the screw, the thread configuration, the number of cortices engaged, the cervical level, or the bone density was associated with the load to failure. Three major subgroups (greatest, intermediate, and lowest pull-out resistance) were identified. The subgroup with the greatest pull-out resistance included only screws with bicortical purchase; the 3.2, 3.5, and 4.5-millimeter cortical-bone screws and the 3.5-millimeter cancellous-bone screw were in this subgroup. Regardless of the thread configuration, no screw with unicortical purchase was in the group with the greatest pull-out resistance. Two of the three values in the subgroup with the lowest pull-out resistance were for the 3.5-millimeter self-tapping screw (with unicortical or bicortical purchase). The cancellous-bone density of the vertebral body was not associated with pull-out resistance and it did not vary significantly according to the cervical level, with the numbers available. However, the pull-out resistance of the screws varied significantly (p = 0.004) by level: it was the greatest at the fourth cervical level, decreasing cephalad and caudad to that level.


Refining Vegetable Oils: Chemical and Physical Refining.
This review presents recent technologies involved in vegetable oil refining as well as quality attributes of crude oils obtained by mechanical and solvent extraction. Usually, apart from virgin oils, crude oils cannot be consumed directly or incorporated into various food applications without technological treatments (refining). Indeed, crude oils like soybean, rapeseed, palm, corn, and sunflower oils must be purified or refined before consumption. The objective of such treatments (chemical and physical refining) is to get a better quality, a more acceptable aspect (limpidity), a lighter odor and color, longer stability, and good safety through the elimination of pollutants while minimizing oil loss during processing. However, the problem is that refining removes some essential nutrients and often generates other undesirable compounds such as 3-MCPD-esters and trans-fatty acids. These compounds directly influence the safety level of refined oil. Advantages and drawbacks of both chemical and physical refining were discussed in the light of recent literature. Physical refining has several advantages over chemical one.


Supplementation of micronutrients in children and food fortification initiatives in Sri Lanka: benefits versus risks.
In recent decades, Sri Lanka has made substantial progress in reducing the burden of micronutrient deficiencies in children by the provision of vitamin A megadose and micronutrient supplementation programs for children of 6-23 months, along with universal iodization of salt. Consumption of voluntarily fortified foods by children was also considerably increased. The objective of our study here was to review such interventions, which are beneficial in childhood, and to assess the risk of toxicity due to excessive intakes of iron, vitamin A, and iodine. Our analysis was performed using data from two national micronutrient surveys, market surveys, and key informant interviews. Data on coverage, usage, and nutrient content of certain foods were compiled to gauge consumption of iron, vitamin A, and iodine among children. We found that the severity of anemia and vitamin A and iodine deficiencies declined from moderate-to-severe and that supplementation and fortification can lead to an excess of vitamin A that may cause toxicity, while iron and iodine deficiency appears to be no longer a public health concern in Sri Lanka. We recommend review and scaling back of national supplementation programs and monitoring of fortification initiatives to prevent micronutrient toxicity in the future.


Catalyst-Free Rearrangement of Allenyl Aryldiazoacetates into 1,5-Dihydro-4H-pyrazol-4-ones.
Phenylpropargyl diazoacetates exist in equilibrium with 1-phenyl-1,2-dien-1-yl diazoacetate - allenes that are rapidly formed at room temperature through 1,3-acyloxy migration catalyzed by gold(I) or gold(III) compounds, and these catalysts react solely with the π-donor rather than with the diazo group. The product allene of the aryldiazoacetates undergoes rearrangement that is not catalyzed by gold in which the terminal nitrogen of the diazo functional group adds to the central carbon of the allene, initiating a sequence of bond-forming reactions, resulting in the production of 1,5-dihydro-4H-pyrazol-4-ones in good yields. These 1,5-dihydro-4H-pyrazol-4-ones undergo intramolecular 1,3-acyl migration to form an equilibrium mixture and can quantitatively transfer the acyl group to an external nucleophile with formation of 4-hydroxypyrazoles. Reactions of phenylpropargyl phenyldiazoacetates catalyzed by cationic gold complexes are initiated at the diazo functional group to form a gold carbene whose subsequent cascade process (intramolecular addition, then aromatic substitution) results in the formation of a product that is uniquely characteristic of this pathway.


[Characteristic vibration analysis of M-RNA nucleic acid bases complexes (M = Ca+ and Mg+) by DFT].
A density functional investigation of the interaction between calcium and magnesium univalent cations and RNA pyrimidine base (cytosine, thymine and uracil) was performed to determine geometric coordinates and free energies for all possible stable isomers at B3LYP/6-311 + G (2df, 2p) level. The most stable isomers C1M, T1M and U1M (M = Ca+ and Mg+) with the lowest free energy among the same pyrimidine base tautomers were calculated to determine the characters of infrared vibrations. According to the results, two characteristic infrared vibrations at wave numbers 1,684 and 1,765 cm(-1) were found for single pyrimidine base C1, at 1,747 and 1,792 cm(-1) for T1, 1,763 and at 1,796 cm(-1) for U1. In addition, spectrum shifts were found when the cations interact with the pyrimidine base tautomers. For deeper analysis, we found that when the stable complexes are formed, the cations are prone to act on the oxygen atoms, and cause the vibrational frequencies to change, the spectral lines belonging to the vibration of C--O--M turn out to redshift and the others turn out to blueshift. When the stable complex C1M is formed, the characteristic infrared vibration at 1,684 cm(-1) mainly caused by the ring's vibration turns out to blueshift about 10 cm(-1), and the another characteristic vibration of 1,765 cm(-1) caused by vibration of bond C--O with oxygen atom acting on cations directly turns out to redshift by 112 cm(-1) for complex C1Ca+ and by 110 cm(-1) for C1Mg+. When the stable complexes T1M are formed, the characteristic vibration of bond C--O--M turns out to redshift about 130 cm(-1) and the vibration of bond C--O turns out to blueshift about 55 cm(-1). When the stable complexes U1M are formed, the vibration of bond C--O--M turns out to redshift about 90 cm(-1) and about 50 cm(-1) for another C--O. The characteristic infrared vibration frequencies are changed obviously when tautomers act on the cations, which is mainly because cations take part in molecule's vibrations and change the force constants and reduced masses.


Safety Evaluation of Natural Drugs in Chronic Skeletal Disorders: A Literature Review of Clinical Trials in the Past 20 years.
Chronic skeletal disorders (CSDs), including degenerative diseases such as osteoporosis (OP) and autoimmune disorders, have become a leading cause of disability in an ageing society, with natural drugs being indispensable therapeutic options. The clinical safety evaluation (CSE) of natural drugs in CSDs has been given priority and has been intensively studied. To provide fundamental evidence for the clinical application of natural drugs in the elderly population, clinical studies of natural drugs in CSDs included in this review were selected from CNKI, Web of Science, PubMed, Science Direct and Google Scholar since 2001. Seventeen randomized controlled trials (RCTs) met our inclusion criteria: four articles were on OP, seven on osteoarthritis (OA), four on rheumatoid arthritis (RA) and two on gout. Common natural drugs used for the treatment of OP include Epimedium brevicornu Maxim [Berberidaceae], Dipsacus asper Wall ex DC [Caprifoliaceae] root, and Phalaenopsis cornu-cervi (Breda) Blume & Rchb. f[ Orchidaceae], which have been linked to several mild adverse reactions, such as skin rash, gastric dysfunction, abnormal urine, constipation and irritability. The safety of Hedera helix L [Araliaceae] extract, Boswellia serrata Roxb [Burseraceae] extract and extract from perna canaliculus was evaluated in OA and upper abdominal pain, and unstable movements were obsrerved as major side effects. Adverse events, including pneumonia, vomiting, diarrhoea and upper respiratory tract infection, were reported when RA was treated with Tripterygium wilfordii, Hook. F [Celastraceae][TwHF] polyglycosides and quercetin (Capsella bursa-pastoris (L.) Medik [Brassicaceae]). The present review aimed to summarize the CSE results of natural drugs in CSDs and could provide evidence-based information for clinicians.


Dental implants: early versus standard two-stage loading (animal study).
Direct bone formation on the implant surface is a treatment goal in implant dentistry. It was always thought that a healing period of 3 months for the lower jaw and 5-6 months for the upper jaw was required for osseointegration to occur. Recent studies, however, show that with the early loading protocol, osseointegration is possible as well. The goal of this study was to evaluate clinical, histologic, and histomorphometric parameters of implants with early loading protocols and implants that did not undergo the early loading protocol. In this experimental study, the first to the fourth premolar teeth were extracted from the lower jaws of 3 dogs. After a healing period of 3 months, 12 BioHorizons internal implants 4.5 × 10.5 mm were placed in the mandible of the dogs. The implant stability quotient (ISQ) was recorded. After 3 weeks, half of the implants were exposed, and after recording ISQ, polycarbonate crowns were placed on them and occlusion was adjusted so that there was no contact in centric occlusion and no lateral movement with the opposing teeth. After 3 months, the ISQs were recorded for all the implants. Bleeding upon probing and pocket depths were measured for the early loading implants. All the implants were removed using a trephine bur, and cross-sections of 150 μm were prepared, from which the bone implant contact (BIC) and the type of bone around them were obtained. Statistical analysis was conducted with independent t test, paired t test, and repeated analysis of variance. The BIC for the early loaded group was 46.17% ± 12.89%, and for the unloaded group was 44.4% ± 10.45%. This difference was not statistically significant (P = .811). The ISQ for the implants in the early loaded group (before they were removed) was 71 ± 7.35 and that of the unloaded group was 66.75 ± 11.86 .These differences were statistically insignificant. With regard to the result of this study, and the fact that the 2 groups showed no statistically significant differences in a number of major aspects, such as BIC and ISQ, it seems possible to load implants with an earlier than usual protocol with no adverse effects on implant success. It is necessary, however, to follow certain protocols for this type of loading.


Monoclonal B-cell lymphocytosis is closely related to chronic lymphocytic leukaemia and may be better classified as early-stage CLL.
The World Health Organization classification uses a cut-off point of 5·0 × 10(9)/l cells with a chronic lymphocytic leukaemia (CLL)-phenotype in peripheral blood to discriminate between monoclonal B-lymphocytosis (MBL) and B-CLL. This study analysed 298 MBL patients by multi-parameter flow cytometry, chromosome banding analysis (CBA)/fluorescence in situ hybridization (FISH), and IGHV mutation status and compared them with 356 CLL patients. In MBL, CBA more frequently revealed a normal karyotype and FISH identified less frequently del(6q), del(13q) (as sole alterations), and del(17)(p13). Within the MBL cohort, a shorter time to treatment (TTT) was found for ZAP-70-positivity, 14q32/IGH-translocations (CBA), del(11)(q22·3) (FISH) and unmutated IGHV status. Higher CD38 and ZAP-70 expression, del(11)(q22·3) (FISH), trisomy 12 (FISH), and 14q32/IGH-translocations (CBA) were correlated with a shorter TTT in the combined cohort (MBL + CLL); a sole del(13)(q14) (FISH) correlated with longer TTT. Regarding overall survival, unmutated IGHV status and 'other' alterations (CBA) had an adverse impact. There was no correlation between the concentration of CLL-cells and TTT or overall survival. Multivariate analysis confirmed a negative impact on TTT for del(11)(q22·3)/ATM, trisomy 12 (both by FISH), and 14q32/IGH-translocations by CBA. These data emphasize a close relationship between MBL and CLL regarding clinically relevant parameters and provide no evidence to strictly separate these entities by a distinct threshold of clonal B-cells.


Antiproliferative activity and chemical composition of the venom from the Amazonian toad Rhinella marina (Anura: Bufonidae).
Little is known on the composition of Peruvian Amazon toad venoms. The large toad Rhinella marina is common in the cleared tropical forests of the Iquitos region and is regarded as poisonous. The venom from two different populations of R. marina was collected in the Departamento de Loreto, Perú. The samples were assessed for antiproliferative effect and composition. Some 29 compounds were identified or tentatively identified from the venom by spectroscopic and spectrometric means. The main free bufadienolide was marinobufagin 7 while marinobufotoxin 15 and bufalitoxin 9 were the main bufadienolide argininyl diacid derivatives. The alkaloids dehydrobufotenin 28 and bufotenidin 29 were present in both venoms. The main difference in the venoms was the relative ratio of argininyl diacids from bufadienolides to free bufadienolides. The argininyl diacids included derivatives from bufalin, marinobufagin, telocinobufagin, hellebrigenin, resibufogenin and bufotalinin. Four compounds, including undecadienoyl aginine 6 and three argininyl diacids from bufadienolides were tentatively identified for the first time in the samples. The venom showed a strong antiproliferative effect towards MRC-5 normal human lung fibroblasts (0.063-0.247 μg/mL), AGS human gastric adenocarcinoma cells (0.076-0.272 μg/mL), SK-MES-1 human lung cancer cells (0.154-0.296 μg/mL), J82 human bladder carcinoma cells (0.169-0.212 μg/mL), and HL-60 human promyelocytic leukemia (0.071-0.283 μg/mL). The antiproliferative effect is mediated by ROS production and cell cycle arrest in human breast cancer cells (MCF7 and MDA-MB-231). This is the first report on the composition of R. marina venom from the Peruvian Amazon pointing out the need to include different venom samples to get a better picture from the activity and composition of South American toad defense substances.


Biomaterial-Driven Immunomodulation: Cell Biology-Based Strategies to Mitigate Severe Inflammation and Sepsis.
Inflammation is an essential component of a wide variety of disease processes and oftentimes can increase the deleterious effects of a disease. Finding ways to modulate this essential immune process is the basis for many therapeutics under development and is a burgeoning area of research for both basic and translational immunology. In addition to developing therapeutics for cellular and molecular targets, the use of biomaterials to modify innate and adaptive immune responses is an area that has recently sparked significant interest. In particular, immunomodulatory activity can be engineered into biomaterials to elicit heightened or dampened immune responses for use in vaccines, immune tolerance, or anti-inflammatory applications. Importantly, the inherent physicochemical properties of the biomaterials play a significant role in determining the observed effects. Properties including composition, molecular weight, size, surface charge, and others affect interactions with immune cells (i.e., nano-bio interactions) and allow for differential biological responses such as activation or inhibition of inflammatory signaling pathways, surface molecule expression, and antigen presentation to be encoded. Numerous opportunities to open new avenues of research to understand the ways in which immune cells interact with and integrate information from their environment may provide critical solutions needed to treat a variety of disorders and diseases where immune dysregulation is a key inciting event. However, to elicit predictable immune responses there is a great need for a thorough understanding of how the biomaterial properties can be tuned to harness a designed immunological outcome. This review aims to systematically describe the biological effects of nanoparticle properties-separate from additional small molecule or biologic delivery-on modulating innate immune cell responses in the context of severe inflammation and sepsis. We propose that nanoparticles represent a potential polypharmacological strategy to simultaneously modify multiple aspects of dysregulated immune responses where single target therapies have fallen short for these applications. This review intends to serve as a resource for immunology labs and other associated fields that would like to apply the growing field of rationally designed biomaterials into their work.


Combination synchronization of three classic chaotic systems using active backstepping design.
In this paper, an active backstepping design is proposed to achieve combination synchronization between three different chaotic systems: Lorenz system, Chen's system, and Lü system. The proposed method is a systematic design approach and consists in a recursive procedure that interlaces the choice of a Lyapunov function with the design of active control. Numerical simulations are shown to verify the feasibility and effectiveness of the proposed control technique.


Associations of blood lipid-related indices with blood pressure and pulse pressure in middle-aged men.
Low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio is known as a classical atherogenic index. In addition, triglycerides to HDL-C (TGs/HDL-C) ratio and lipid accumulation product (LAP) have been proposed to be good discriminators for cardiometabolic risk. The aim of this study was to determine which lipid index is most strongly associated with blood pressure and pulse pressure. The subjects were 36,536 Japanese men aged 35-60 years who were not receiving drug therapy for dyslipidemia. Relationships of each lipid index with blood pressure and pulse pressure were investigated by using linear and logistic regression analyses. There were significant positive correlations of systolic and diastolic blood pressure and pulse pressure with the lipid-related indices such as LDL-C/HDL-C ratio, TGs/HDL-C ratio, and LAP. The correlations with LAP were significantly stronger than those with the LDL-C/HDL-C ratio and the TGs/HDL-C ratio. Odds ratios (ORs) for hypertension and high pulse pressure in subjects with versus subjects without high levels of each lipid-related index were significantly higher than the reference level of 1.00. The ORs of subjects with versus subjects without high LAP tended to be higher than the ORs of subjects with versus subjects without high LDL-C/HDL-C ratio or high TGs/HDL-C ratio. In the linear and logistic regression analyses, the associations of the lipid-related indices with pulse pressure were weaker than the corresponding associations with blood pressure. LAP shows stronger associations with blood pressure and pulse pressure than the other lipid-related indices and is suggested to be better for discriminating the risk of hypertension.


Identification of inhibitors for putative malaria drug targets among novel antimalarial compounds.
The efficacy of most marketed antimalarial drugs has been compromised by evolution of parasite resistance, underscoring an urgent need to find new drugs with new mechanisms of action. We have taken a high-throughput approach toward identifying novel antimalarial chemical inhibitors of prioritized drug targets for Plasmodium falciparum, excluding targets which are inhibited by currently used drugs. A screen of commercially available libraries identified 5655 low molecular weight compounds that inhibit growth of P. falciparum cultures with EC(50) values below 1.25μM. These compounds were then tested in 384- or 1536-well biochemical assays for activity against nine Plasmodium enzymes: adenylosuccinate synthetase (AdSS), choline kinase (CK), deoxyuridine triphosphate nucleotidohydrolase (dUTPase), glutamate dehydrogenase (GDH), guanylate kinase (GK), N-myristoyltransferase (NMT), orotidine 5'-monophosphate decarboxylase (OMPDC), farnesyl pyrophosphate synthase (FPPS) and S-adenosylhomocysteine hydrolase (SAHH). These enzymes were selected using TDRtargets.org, and are believed to have excellent potential as drug targets based on criteria such as their likely essentiality, druggability, and amenability to high-throughput biochemical screening. Six of these targets were inhibited by one or more of the antimalarial scaffolds and may have potential use in drug development, further target validation studies and exploration of P. falciparum biochemistry and biology.


Dynamic Organization of Hierarchical Memories.
In the brain, external objects are categorized in a hierarchical way. Although it is widely accepted that objects are represented as static attractors in neural state space, this view does not take account interaction between intrinsic neural dynamics and external input, which is essential to understand how neural system responds to inputs. Indeed, structured spontaneous neural activity without external inputs is known to exist, and its relationship with evoked activities is discussed. Then, how categorical representation is embedded into the spontaneous and evoked activities has to be uncovered. To address this question, we studied bifurcation process with increasing input after hierarchically clustered associative memories are learned. We found a "dynamic categorization"; neural activity without input wanders globally over the state space including all memories. Then with the increase of input strength, diffuse representation of higher category exhibits transitions to focused ones specific to each object. The hierarchy of memories is embedded in the transition probability from one memory to another during the spontaneous dynamics. With increased input strength, neural activity wanders over a narrower state space including a smaller set of memories, showing more specific category or memory corresponding to the applied input. Moreover, such coarse-to-fine transitions are also observed temporally during transient process under constant input, which agrees with experimental findings in the temporal cortex. These results suggest the hierarchy emerging through interaction with an external input underlies hierarchy during transient process, as well as in the spontaneous activity.


Photosynthetic Membranes of Porphyridium cruentum: An Analysis of Chlorophyll-Protein Complexes and Heme-Binding Proteins.
Three chlorophyll-protein complexes (CP I, CP III, CP IV) were electrophoretically separated from thylakoids of the eukaryotic red alga Porphyridium cruentum. CP I contained the primary photochemical reaction center of photosystem I as judged by its light-induced reversible absorbance change at 700 nanometers, by its fluorescence emission maximum at 720 nanometers (-196 degrees C), and by the molecular weight of its apoprotein (68,000 daltons). CP III and CP IV appeared to belong with photosystem II as suggested by the absence of light-reversible absorbance at 700 nanometers, by their fluorescence maximum at 690 nanometers (-196 degrees C), and by the presence of a chlorophyll-binding polypeptide with a molecular weight of about 52,000 daltons. CP IV when completely denatured had two additional polypeptides of about 40,000 and 48,000 daltons. All three chlorophyll-protein complexes contained carotenoids: the chlorophyll/carotenoid molar ratio of 15:1 for CP I, and 20:1 for CP III and CP IV. The thylakoid membranes of P. cruentum contained four cytochromes, detected by heme-dependent peroxidase activity, but there was no observed association with the electrophoretically separated chlorophyll-protein complexes.


Multiple Spinal Syphilitic Gummas Diagnosed by Postoperative Histopathology and Antibiotic Responsiveness: A Case Report.
Neurosyphilis is an infection of the central nervous system by Treponema pallidum. Gummatous neurosyphilis, especially spinal syphilitic gumma, is an exceedingly rare manifestation and may be misdiagnosed as other tumors due to its rarity. A 42-year-old man with a medical history of treatment for syphilis presented with rapidly progressive leg paralysis, leg sensory disturbance, and bladder and rectal disturbance. Spinal MRI demonstrated an intradural extramedullary lesion strongly compressing the spinal cord at the T6/7 level, which was accompanied with dural tail sign and perilesional meningeal thickening at the T6-T8 levels. Small intradural extramedullary lesions were also detected at the T1 and T8 levels. Serological and cerebrospinal fluid examinations for syphilis were both positive. In the treatment of spinal syphilitic gumma, the decompression of the spinal cord by lesionectomy followed by postoperative antibiotic treatment is considered to be an optimal procedure in patients with rapid progression of neurological deterioration. In the present case, the symptomatic main lesion that was compressing the thoracic cord was excised by surgery and analyzed by histopathological examination, and another small asymptomatic lesion was resolved by postoperative antibiotic treatment. Spinal syphilitic gumma was diagnosed using both histopathological findings of the surgically resected lesion and another residual lesion that was resolved by postoperative antibiotic treatment.


Recent diabetes issues affecting the primary care clinician.
Diabetes accounts for millions of office visits each year to primary care offices in the United States. Successful care of the patient with type 2 diabetes requires not only focus on glucose management but also on comorbidities such as hypertension, dyslipidemia and obesity which are closely linked to microvascular and macrovascular complications. Primary care clinicians must stay abreast of frequently published diabetes literature and new treatments to care for these increasingly complex patients. Metformin and its effect on B12 absorption continues to be an issue encountered by clinicians in daily clinical practice. There has also been recent discussion regarding the increased risk of diabetes with statins; data to date on this issue have been conflicting. Rosiglitazone continues to face public scrutiny and there are now Food and Drug Administration regulations regarding its increased risk of cardiovascular disease. Liraglutide and saxagliptin represent new treatment options for type 2 diabetes, increasing the available options for treating this complex disease. A review of the primary literature involving these topics is provided.


Neurochemical substances in neurons of the canine intrinsic laryngeal muscles.
The localization of vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), catecholamines (CA) and carbon monoxide (CO) in neurons of the intrinsic laryngeal muscles of the dog was investigated using immunohistochemistry. Cells with VIP-like immunoreactivity were found between the striated muscle fibres of the cricothyroid and posterior cricoarytenoid muscles, some aggregated into a ganglion and some solitary. Neurons with immunoreactivity to haem oxygenase-2 (HO-2), an immunohistochemical marker for CO, were also seen. VIP-or HO-2-negative cells also existed in various numbers in the intramuscular ganglia. No CGRP-like immunoreactive neurons were found although CGRP-like immunoreactive varicose fibres were seen in the intramuscular ganglia. No neurons or fibres immunoreactive to tyrosine hydroxylase (TH), the key enzyme in synthesis of CA, were detected. The exact function of these intramuscular ganglia is yet to be clarified, but they may be sensory neurons.


Social Isolation and Associated Factors in Chinese Adults With Epilepsy: A Cross-Sectional Study.
Objective: We aimed to determine the prevalence of social isolation and associated factors among adults with epilepsy in northeast China. Methods: A cohort of consecutive patients with epilepsy (PWE) from the First Hospital of Jilin University (Changchun, China) was recruited. Demographic and clinical data for each patient were collected during a face-to-face interview. Social isolation was measured using the Berkman-Syme Social Network Index (SNI), and the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and Quality of Life in Epilepsy Inventory (QOLIE-31) were also administered. Multivariate logistic regression analyses were used to determine the factors associated with social isolation in PWE. Results: A total of 165 patients were included in the final analysis. The mean SNI score was 2.56 (SD: 1.19), and 35 patients (21.2%) were socially isolated. In multivariate logistic regression analysis, higher depressive symptom levels (OR = 1.15, 95% CI: 1.003-1.318, P = 0.045) and poorer quality of life (OR = 0.967, 95% CI: 0.935-0.999, P = 0.047) emerged as independent factors associated with social isolation in PWE. Conclusion: Social isolation is common and occurs in approximately one-fifth of PWE. Social isolation is significantly associated with depressive symptoms and poor quality of life in PWE. Patients need to be encouraged to actively integrate with others and reduce social isolation, which may help improve their quality of life.


The 2005 C.T. Rowland Award orthodontic case report.
The C.T. Rowland award is presented annually by the Texas Orthodontic Study Club (formerly "Texas Tweed"). The award was first presented in 1954 in recognition of the group's president, C. T. Rowland. Applicants to the study club, which numbers almost 200 orthodontists from Texas and surrounding states, are required to present five cases for membership. These cases, with before and after records, represent a variety of malocclusions demonstrating the applicants' knowledge and expertise in diagnosing, treating, and finishing cases with quality results. The qualifying committee reviews each applicant's cases and, based on the difficulty of the original malocclusions and the degree of excellence of the finished result, chooses one person to receive their award. The 2005 winner of the C. T. Rowland award is Dr. Kyle Shannon. He is in the exclusive practice of orthodontics in Tulsa, OK.


What Do You Mean by That?! An Electrophysiological Study of Emotional and Attitudinal Prosody.
The use of prosody during verbal communication is pervasive in everyday language and whilst there is a wealth of research examining the prosodic processing of emotional information, much less is known about the prosodic processing of attitudinal information. The current study investigated the online neural processes underlying the prosodic processing of non-verbal emotional and attitudinal components of speech via the analysis of event-related brain potentials related to the processing of anger and sarcasm. To examine these, sentences with prosodic expectancy violations created by cross-splicing a prosodically neutral head ('he has') and a prosodically neutral, angry, or sarcastic ending (e.g., 'a serious face') were used. Task demands were also manipulated, with participants in one experiment performing prosodic classification and participants in another performing probe-verification. Overall, whilst minor differences were found across the tasks, the results suggest that angry and sarcastic prosodic expectancy violations follow a similar processing time-course underpinned by similar neural resources.


Efficacy of pivmecillinam for treatment of lower urinary tract infection caused by extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae.
To evaluate the clinical and bacteriological efficacy of pivmecillinam against lower urinary tract infection (UTI) caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae, patients treated for lower UTI with pivmecillinam (n=8) were studied. Patients treated with nitrofurantoin (n=3) and trimethoprim (n=3) or a combination of these agents with pivmecillinam (n=3) were included as a control group. Antimicrobial susceptibility was determined with EUCAST methodology. Bacteriologic cure was defined as <10(3) CFU/ml at follow-up (30 days), and clinical cure as resolved UTI symptoms after completed treatment. All patients receiving pivmecillinam had good clinical response (8/8), but bacteriological cure rates were low (2/8). However, none of the patients with persisting bacteriuria had a relapse of UTI symptoms within 6 months. All isolates were susceptible to the given antimicrobial. Most isolates belonged to the CTX-M-1 group (n=11, 65%) or CTX-M-9-group (n=4, 24%). Four E. coli isolates belonged to the international clone O25b-ST131 (25%). In conclusion, pivmecillinam had good clinical activity against lower UTI caused by ESBL-producing Enterobacteriaceae, but bacteriological cure rates were low. The persistent bacteriuria appears to be of little clinical importance, but larger clinical studies are needed to determine the usefulness of pivmecillinam in infections caused by ESBL-producing bacteria.


Artificial nanograting woven by self-assembled nanowires.
We report on a new simple route to realize a high resolution nanograting. By adopting an InAlGaAs matrix and strain-compensated technique, we have proved that a uniform self-assembled InAs nanowire array can be fabricated by molecular beam epitaxy (MBE). A nanograting woven by self-assembled semiconductor nanowires shows a conspicuous diffraction feature. The good agreement between the theoretical and experimental values of diffraction peak positions indicates that a uniform nanowire array is a promising nanograting. This simple one-step MBE growth method will open exciting opportunities for the field of clever optics design.


Mild traumatic brain injury elicits time- and region-specific reductions in serotonin transporter protein expression and uptake capacity.
The monoamine neurotransmitter serotonin (5-HT) is important for the regulation of behavior, and aberrations in 5-HT signaling are linked to several neuropsychiatric and neurodevelopmental disorders. 5-HT signaling is dependent on and tightly regulated by the functional activity of the 5-HT transporter (SERT). Neurotrauma is known to structurally and functionally impact 5-HT neuronal tracts and 5-HT signaling; however, the extent to which various forms of neurotrauma alter homeostatic 5-HT signaling through the modulation of SERT expression and/or functional uptake capacity is currently not well characterized. We aimed to better characterize the protein expression and uptake activity of SERT following mild traumatic brain injury (mTBI). A murine model of blast-induced mTBI was utilized to characterize alterations in SERT expression and function following injury. mTBI was found to decrease (≈26%) the protein levels of SERT 3 days postinjury (DPI) in the dorsal raphe nucleus (DRN), the primary locale of 5-HT neuronal cell bodies within the central nervous system. Concomitant reductions in midbrain SERT-dependent radiolabeled 5-HT uptake were observed 3 DPI (≈24%). No alterations in SERT expression were observed 10 DPI in the DRN. Additionally, no alterations in SERT expression or function were observed in prefrontal cortex samples at any time point observed. This data reveals time- and location-dependent alterations in SERT expression and function following mTBI. These studies illustrate the critical importance of ongoing research efforts to characterize the molecular effects of various forms of neurotrauma on SERT protein expression and function, which may yield novel drug targets within 5-HT systems.


Inhibition of Listeria monocytogenes by in situ produced and semipurified bacteriocins of Carnobacterium spp. on vacuum-packed, refrigerated cold-smoked salmon.
Listeria monocytogenes inhibition by Carnobacterium strains and crude bacteriocins on sterile and commercial vacuum-packed cold-smoked salmon stored at 4 degrees C and 8 degrees C was investigated. Carnobacterium piscicola V1 was bactericidal against L. monocytogenes at the two temperatures, whereas Carnobacterium divergens V41 presented a bacteriostatic effect. C. piscicola SF668 delayed L. monocytogenes growth at 8 degrees C and had a bacteriostatic effect at 4 degrees C. Listeria growth was not affected by a non-bacteriocin-producing C. piscicola. Crude extracts of piscicocins were bactericidal at 4 degrees C and 8 degrees C. Listeria growth was delayed by divercin V41 at 8 degrees C and was inhibited at 4 degrees C. Nisin delayed Listeria growth at 8 degrees C and was bacteriostatic at 4 degrees C. The present study demonstrates that L. monocytogenes growth could be prevented on vacuum-packed cold-smoked salmon by Carnobacterium and associated bacteriocins at chilled temperatures. Moreover, no product spoilage could be observed with the use of such bacteriocin-producing strains as demonstrated by good sensorial analyses and low biogenic amine production.


Organometallic Probe for the Electronics of Base-Stabilized Group 11 Metal Cations.
A number of trimetalloborides have been synthesized through the reactions of base-stabilized coinage metal chlorides with a dimanganaborylene lithium salt in the hope of using this organometallic platform to compare and evaluate the electronics of these popular coinage metal fragments. The adducts of Cu(I), Ag(I), and Au(I) ions, stabilized by tricyclohexylphosphine (PCy3), N-1,3-bis(4-methylphenyl)imidazol-2-ylidene (ITol), or 1-(2,6-diisopropylphenyl)-3,3,5,5-tetramethylpyrrolidin-2-ylidene (CAAC), with [{Cp(CO)2Mn}2B](-) were studied spectroscopically, structurally, and computationally. The geometries of the adducts fall into two classes, one symmetric and one asymmetric, each relying on the combined characteristics of both the metal and ligand. The energetic factors proposed as the causes of the structural differences were investigated by ETS-NOCV (extended transition state-natural orbitals for chemical valence) analysis, which showed the final geometry to be controlled by the competition between the tendency of the coinage metal to adopt a higher or lower coordination number and the willingness of the cationic fragment to participate in back-bonding interactions.


[Process study on hysteresis of vegetation cover influencing sand-dust events].
Data analysis from satellite and weather stations during 1982-2000 shows nonlinear relationship between vegetation cover and sand-dust events is present in most part of China. Vegetation cover ratio in summer can impact significantly on the frequency of sand-dust storms from winter to spring in the source regions of sand-dust events. It is not quite clear about the hysteresis that vegetation cover in summer influence sand-dust events during winter and spring. A quasi-geostrophic barotropic model is used under the condition of 3 magnitude of frictional coefficient to investigate the cause of the hysteresis. Wind velocity shows a greatest decline at 90% during 72 h as initial wind velocity is 10 m/s for magnitude of frictional coefficient between atmosphere and water surface, greatest decline at 100% during 18 h for magnitude of frictional coefficient between atmosphere and bare soil and a 100% reduction of wind speed during 1 h for magnitude of frictional coefficient between atmosphere and vegetation cover. Observation and simulation prove that residual root and stem from summervegetation are one of factors to influence sand-dust events happened during winter and spring. Air inhibition from residual root and stem is a most important reason for hysteresis that vegetation cover influence sand-dust events.


Cell-attached patch clamp study of the electropermeabilization of amphibian cardiac cells.
Potential gradients imposed across cell or lipid membranes break down the insulating properties of these barriers if an intensity and time-dependent threshold is exceeded. Potential gradients of this magnitude may occur throughout the body, and in particular in cardiac tissue, during clinical defibrillation, ablation, and electrocution trauma. To study the dynamics of membrane electropermeabilization a cell-attached patch clamp technique was used to directly control the potential across membrane patches of single ventricular cells enzymatically isolated from frog (Rana pipiens) hearts. Ramp waveshapes were used to reveal rapid membrane conductance changes that may have otherwise been obscured using rectangular waveshapes. We observed a step increase (delta t less than 30 microseconds) or breakdown in membrane conductance at transmembrane potential thresholds of 0.6-1.1 V in response to 0.1-1.0 kV/s voltage ramps. Conductance kinetics on a sub-millisecond time scale indicate that breakdown is preceded by a period of instability during which the noise and amplitude of the membrane conductance begin to increase. In some cells membrane breakdown was observed to be fully reversible when using an intershock interval of 1 min (20-23 degrees C). These findings support energetic models of membrane electropermeabilization which describe the formation of membrane pores (or growth of existing pores) to a conducting state (instability), followed by a rapid expansion of these pores when the energy barrier for the formation of hydrophilic pores is overcome (breakdown).


Acylation of Lignin with Different Acylating Agents by Mechanical Activation-Assisted Solid Phase Synthesis: Preparation and Properties.
Acylated lignins with substituents consisting of different lengths of carbon chains were prepared by a mechanical activation-assisted solid phase synthesis (MASPS) technology with a customized stirring ball mill as a reactor. The structures and properties were analyzed by UV/Vis, FTIR, NMR, SEM, DSC, and TG. The results showed that the acylated lignins were successfully prepared with either non-cyclic or cyclic anhydrides as the acylating agents. Both aliphatic hydroxyl and phenolic hydroxyl groups of lignin reacted with non-cyclic anhydrides, and different reactivity of acylating agents resulted in different relative contents of phenolic and aliphatic substituents in the products. The reactivity of the cyclic anhydrides was weaker than that of the non-cyclic anhydrides, and the reactivity of the acylating agents decreased with increasing carbon chain length and unsaturated bonds of acyl groups. All of the acylated lignins except maleylated lignin had a lower glass transition temperature (Tg) than the original lignin. The acylated lignins prepared with non-cyclic anhydrides had better thermal stability than original lignin, and the thermal stability increased, but Tg decreased with an increasing chain length of the acyl groups. The acylated lignins prepared with cyclic anhydrides had higher a Tg than those with non-cyclic anhydrides with the same carbon number, and the thermal stability was not obviously improved.


[Diagnostic and therapeutic strategies in exacerbations of chronic bronchitis in city practice].
The consensus conference convened by the French Language Society for Infectious Disease at Lille in 1991 stressed the fact that two germs were most often the cause of exacerbation in chronic bronchitis (Streptococcus pneumoniae and Haemophilus influenzae) and that antibiotic therapy was the "safe solution" and that the first intention treatment should be either penicillin A, a first generation cephalosporin or a macrolide for the first 8-10 days. A chest x-ray was recommended if there was the slightest doubt about co-existing parenchymal disease with a reevaluation around the 7th day and a prescription of penicillin A plus a beta-lactamase inhibitor or a second or third generation cephalosporin in case of failure. The aim of this study was to assess the diagnostic and therapeutic attitudes of general practitioners when faced with exacerbation in chronic bronchitis in an adult of 60 without severe signs and to find out the antibiotic of first choice and also the antibiotic to be used if the first treatment failed. One hundred doctors were drawn at random from a list of general practitioners in Bordeaux. They were requested to reply to a questionnaire on the strategy of first choice antibiotic and the means of reassessment of the treatment after it had been instituted and the strategy used when faced with a patient who did not improve after the initial treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


Purification and characterization of membrane-bound phosphatidylinositol kinase from rat brain.
A membrane-bound phosphatidylinositol (PI) kinase was purified from rat brain. The enzyme was solubilized with Triton X-100 from salt-washed membrane and purified 11,183-fold, with a final specific activity of 150 nmol/min/mg of protein. Purification steps included several chromatography using Q-Sepharose Fast Flow, cellulose phosphate, Toyopearl HW 55 and Affi-Gel Blue. The purified PI kinase had an estimated molecular weight of 80,000 by gel filtration and 76,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The purified kinase phosphorylated only PI and did not phosphorylate phosphatidylinositol 4-phosphate or diacylglycerol. Km values for PI and ATP were found to be 115 and 150 microM, respectively. The enzyme required Mg2+ (5-20 mM) or Mn2+ (1-2 mM) for activity, was stimulated by 0.1-1.0% (w/v) Triton X-100, and completely inhibited by 0.05% sodium dodecyl sulfate. The enzyme activity showed a broad pH optimum at around 7.4. The enzyme utilized ATP and not GTP as phosphate donor. Nucleoside triphosphates other than ATP and diphosphates significantly inhibited the kinase activity. However, inhibitory effects of adenosine, cAMP, and quercetin were weak.


Anti-N-methyl-D-aspartate receptor encephalitis: a common cause of encephalitis in the intensive care unit.
Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDAR encephalitis) is the most common type of immune-mediated encephalitis. This study aimed to assess the incidence and mortality of anti-NMDAR encephalitis in intensive care unit (ICU) to evaluate the clinical manifestations, laboratory findings, managements and outcomes, and to compare these characteristics with patients with non-anti-NMDAR encephalitis admitted to ICU. Patients admitted to the neurological ICU with suspected encephalitis were included between January 1, 2012 and July 31, 2015. Cerebrospinal fluid (CSF) of enrolled patients was screened for anti-NMDAR antibodies using a cell-based assay. 72 critically ill patients with encephalitis of uncertain etiology were investigated, and 16 patients were positive for anti-NMDAR antibodies in CSF. Compared to patients with non-anti-NMDAR encephalitis, patients with anti-NMDAR encephalitis were younger, more likely to present with the psychiatric symptoms, dyskinesia, and autonomic dysfunction, and had longer ICU stays. The abnormal movements were so difficult to control that complicated the management. The outcome was favorable in ten patients 1 year after the disease onset, and the mortality was as high as 25 % overall. The incidence of anti-NMDAR encephalitis is high among critically ill patients with encephalitis of uncertain etiology. Controlling dyskinesia proved to be a challenge. Persistent dysautonomias were additional difficult to manage confounders. Same points being highlighted in this study may aid clinicians in the management of patients with anti-NMDAR encephalitis in intensive care practice.


[Effects of socio-environmental factors on neurocognitive performance in premature or low-birth weight preschoolers].
Severely preterm neonates (gestational age < or = 32 weeks) and/or very low birth weight (VLBW, with weight at birth < or = 1500 g) are 2% of all newborns, with a rising incidence due to the increase of multiple gestations and of pregnancies at advanced age. These neonates may be affected by severe neurological pathologies (6-10% of cases), but they often have minor disabilities (such as distractibility, hyperactivity, learning and social competence disabilities, deficit of motor development) difficult to be early diagnosed, and frequently recognized only at pre-school or school age. A review of the current knowledge about the effects of potential risk factors responsible for deficits of neurocognitive development in pre-school age and for postnatal distress of mothers, and their inter-correlations, is reported.


Composition of fat in enteral diets can influence outcome in experimental peritonitis.
An animal model of protracted acute peritonitis was used to study the effects on survival of different amounts and types of dietary fat. Guinea pigs (n = 132) were provided with gastrostomies and allowed to recover. Intraperitoneal osmotic pumps were then placed, allowing for effusion of viable bacteria during the next week. Three days after pump implantation, the animals were randomized to receive one of nine diets, differing only in fat content (3.5%, 14%, or 56% of total calories) and fat composition (100% Microlipid [primarily safflower oil, rich in linoleic acid], 100% MaxEPA [fish oil containing 35% omega-three fatty acids], or a 50:50 mixture of both oils). At the end of 2 weeks, survival rates were compared. Among all types of fat used, the level of fat did not affect outcome, with survival rates of 13% (6 of 45) at the low level of fat used, 30% (13 of 44) at the medium level, and 26% (11 of 43) at the high level (P greater than 0.10). However fat composition significantly influenced survival across all levels of fat, with a 39% (17 of 44) survival rate in the groups given equal amounts of Microlipid and MaxEPA, compared either to 21% (9 of 44) for the 100% Microlipid groups, or to 9% (4 of 44) for the 100% MaxEPA groups (p less than 0.05). A second experiment was performed with 58 animals fed five different mixtures of fats, all at 14% of total calories. Diets were made with fat ratios of 100:0, 75:25, 50:50, 25:75, and 0:100 Microlipid to MaxEPA. The survival rate in the 50:50 group was 83% (10 of 12), which is significantly higher than the survival rates with any of the others (p less than 0.05). It is concluded that the amount of fat in the diet does not strongly influence outcome in this model. However an equal mixture of safflower and fish oils significantly improves survival rates compared to diets made with single-oil preparations.


8-Aminoquinolines active against blood stage Plasmodium falciparum in vitro inhibit hematin polymerization.
From the Walter Reed Army Institute of Research (WRAIR) inventory, thirteen 8-aminoquinoline analogs of primaquine were selected for screening against a panel of seven Plasmodium falciparum clones and isolates. Six of the 13 8-aminoquinolines had average 50% inhibitory concentrations between 50 and 100 nM against these P. falciparum clones and were thus an order of magnitude more potent than primaquine. However, excluding chloroquine-resistant clones and isolates, these 8-aminoquinolines were all an order of magnitude less potent than chloroquine. None of the 8-aminoquinolines was cross resistant with either chloroquine or mefloquine. In contrast to the inactive primaquine prototype, 8 of the 13 8-aminoquinolines inhibited hematin polymerization more efficiently than did chloroquine. Although alkoxy or aryloxy substituents at position 5 uniquely endowed these 13 8-aminoquinolines with impressive schizontocidal activity, the structural specificity of inhibition of both parasite growth and hematin polymerization was low.


The JIM Interview. Lee Goldman, MD.
In early 1995, Lee Goldman, MD, left his post as chief medical officer at the Brigham and Women's Hospital in Boston to become the chairman of medicine at the University of California, San Francisco. A well-respected clinical epidemiologist, Goldman has been among the leading proponents of utilizing critical pathways to improve the efficiency of clinical care. His appointment as leader of a department steeped in a strong tradition of basic research was widely seen as another marker in the ascendancy of the field of health services research. However, in just his first year, Goldman has been active in working to further solidify his department's strong basic research foundation as well as expand its research scope, all in what many consider to be the most difficult and volatile of managed care markets. Interviewed on the wards of the UCSF medical center, Goldman reflected on the highly dynamic managed care environment of northern California, and the need to adapt medical training to the rules of a new era in health care.


A RecA-mediated exon profiling method.
We have developed a RecA-mediated simple, rapid and scalable method for identifying novel alternatively spliced full-length cDNA candidates. This method is based on the principle that RecA proteins allow to carry radioisotope-labeled probe DNAs to their homologous sequences, resulting in forming triplexes. The resulting complex is easily detected by mobility difference on electrophoresis. We applied this exon profiling method to four selected mouse genes as a feasibility study. To design probes for detection, the information on known exonic regions was extracted from public database, RefSeq. Concerning the potentially transcribed novel exonic regions, RNA mapping experiment using Affymetrix tiling array was performed. As a result, we were able to identify alternative splice variants of Thioredoxin domain containing 5, Interleukin1beta, Interleukin 1 family 6 and glutamine-rich hypothetical protein. In addition, full-length sequencing demonstrated that our method could profile exon structures with >90% accuracy. This reliable method can allow us to screen novel splice variants from a huge number of cDNA clone set effectively.


Do Tangential Finger Forces Utilize Mechanical Advantage During Moment of Force production?
This study investigated the beneficial effects of the utilization of mechanical advantage (MA) of finger tangential forces during the moment production. Subjects produced the resistive moment of force against the external torque while the moment arms of the tangential forces were systematically changed. We observed a relatively large contribution to the net moment by the tangential forces with the increased moment arms, whereas the vector sum of normal and tangential forces decreased. The indices of multi-finger coordination for the stabilization of the moment of forces and force direction increased with the moment arms. The current results provide evidence that the utilization of MA is associated with both the efficiency of force production and the stabilization of performance variables.


Protein anatomy: structure and function of peptide fragments corresponding to the secondary structure units of barnase.
Globular proteins can be decomposed into several modules or secondary structure units. It is useful to investigate the functions of such structural units in order to understand the folding units of proteins. In our previous work, barnase was divided into six peptide fragments corresponding to modules, and some of them were shown to have RNA-binding and RNase activity [Yanagawa, et al. (1993) J. Biol. Chem. 268, 5861-5865]. Barnase mutant proteins obtained by permutation of the structural units also had RNase activity [Tsuji, T. et al. (1999) J. Mol. Biol. 286, 1581-1596]. Here we investigated the structure and function of peptide fragments corresponding to secondary structure units of barnase. The results of circular dichroism spectroscopy indicated that some of the peptide fragments form helical structures in aqueous solutions containing over 30% 2,2,2-trifluoroethanol, and the S6 (94-110) peptide fragment is induced to form a beta-sheet structure in the presence of RNA. The S6 peptide fragment forms aggregate complexes with RNA. Electron microscopic analysis showed that the aggregate complexes were comprised of filaments. These results indicate that not only modules but also secondary structure units dissected from a globular protein have functional and structure-forming capabilities.


Platelet monoamine oxidase activity in Down's syndrome.
The activity of platelet monoamine oxidase in Down's syndrome cases was significantly lower than that of controls. This difference was found for both males and females, and with tyramine, tryptamine and beta-phenethylamine as substrate. The Km values of the monoamine oxidase towards tryptamine as substrate from controls and Down's syndrome patients were similar.


Comprehensive Echocardiographic Findings in Critically Ill COVID-19 Patients With or Without Prior Cardiac Disease.
Coronavirus disease 2019 (COVID-19) presents with a spectrum of disease severity, the most serious cases requiring intensive care. Echocardiography is a front-line tool in evaluating cardiovascular complications of COVID-19 in the intensive care unit (ICU); we analyzed transthoracic echocardiograms obtained from this patient population with state-of-the-art ultrasound technology. All patients with COVID-19 requiring ICU admission on whom a transthoracic echocardiogram was obtained were included in the study. Focused transthoracic protocols were performed by experienced sonographers. Echocardiographic variables, including speckle-tracking echocardiography, were collected and analyzed. Clinical information was obtained from the electronic medical record. Patients were followed until discharge. Of 52 total patients (mean age: 59.9 ± 11.6 years), 59.6% were male and 15 (29%) had known prior cardiac disease. Cardiac complications identified on echocardiography were prevalent, occurring in 55.7% of patients. Patients with known prior cardiac disease were more likely to have new or worsening left ventricular dysfunction. Right ventricular dysfunction was the most common abnormality (assessed qualitatively in 18 cases and with advanced echocardiographic methods in 34 cases). Known prior cardiac disease, right ventricular enlargement, and pulmonary hypertension were significantly associated with morbidity and mortality. Patients requiring intensive care for COVID-19 face significant morbidity and mortality, and cardiac complications occur in the majority of patients admitted to the ICU with COVID-19. Those with known prior cardiac disease fare worse, and other echocardiographic findings (right ventricular enlargement, pulmonary hypertension) are also associated with worse outcomes. State-of-the-art echocardiography performed by experienced sonographers can be critical to identifying cardiac complications and guiding ICU strategy.