[Is there any alternative for the heart transplantation in patients with cardiac insufficiency of terminal stage?].
The heart transplantation constitutes the method of choice in the treatment of patients, suffering heart insufficiency, tolerant to medicinal therapy. Nevertheless, the donor's organs deficiency problem makes it necessary to search for methods of surgical treatment, which are alternative to transplantation and which would secure the patients life span prolongation as well as the quality of life improvement. New approach in surgical treatment of patients, suffering severe cardiac insufficiency have proposed Brazilian surgeon R. Batista. Experience of surgical treatment of 37 patients with dilatational cardiomyopathy and severe cardiac insufficiency (functional class III-IV, NYHA) is presented. In these patients surgical remodelling of left ventricle was done together with local myocardium plasty between papillary muscles base of mitral and tricuspid valves. Fair immediate and late results are noted.


Diagnostic ability of computed tomography to evaluate external root resorption in vitro.
The aim of this study was to evaluate the diagnostic ability of CT to detect simulated external root resorption defects. External root resorption defects of different sizes and in different locations were simulated in 59 human mandibular incisors. Cavities simulating root resorption defects of 0.6 mm, 1.2 mm, or 1.8 mm in diameter and 0.3 mm, 0.6 mm, or 0.9 mm in depth (small, medium and large defects) were drilled in the cervical, middle and apical thirds of buccal surfaces. Axial CT was used to obtain cross-sectional images of the teeth, and 177 root thirds were assessed by a blinded observer. Of the 131 cavities, 117 were detected (89%). 32 of the 44 (72.72%) cavities located in the apical third were identified. A statistically significant difference (P<0.01) was found between the sizes of defects examined in the apical third. The evaluation of CT diagnostic ability revealed high sensitivity and excellent specificity. However, small cavities located in the apical third were more difficult to detect than all other cavities.


Global and local contexts: the Northern Ogoja Leprosy Scheme, Nigeria, 1945-1960.
Deriving funding from missionary sources in Ireland, Britain and the USA, and from international leprosy relief organizations such as the British Empire Leprosy Relief Association (BELRA) and drawing on developing capacities in international public health under the auspices of WHO and UNICEF through the 1950s, the Roman Catholic Mission Ogoja Leprosy Scheme applied international expertise at a local level with ever-increasing success and coverage. This paper supplements the presentation of a successful leprosy control program in missionary narratives with an appreciation of how international medical politics shaped the parameters of success and the development of therapeutic understanding in the late colonial period in Nigeria.


Evaluation of a four-drug, three-antibiotic, nonbismuth-containing "concomitant" therapy as first-line Helicobacter pylori eradication regimen in Greece.
The eradication rates of Helicobacter pylori (H. pylori) with standard treatments are decreasing worldwide as in Greece. Studies with new antibiotic combinations are needed to find better methods of eradication. Therefore, the aim of this study was to evaluate efficacy and tolerability of a 10-day, four-drug, three-antibiotic, nonbismuth-containing concomitant regimen. This is a prospective, open-label, multicenter study that included 131 patients infected with H. pylori. All patients were diagnosed with peptic ulcer disease or nonulcer dyspepsia by endoscopy. H. pylori infection was established by at least two positive tests among rapid urease test, gastric histology, and (13) C-urea breath test. For 10 days, all patients received esomeprazole 40mg, amoxycillin 1000mg, clarithromycin 500mg, and metronidazole 500mg, all b.d. eradication was assessed with (13) C urea breath test 8weeks after the start of treatment. Intention-to-treat and per-protocol eradication rates were determined. One hundred and twenty-seven of the 131 patients completed the study. At intention-to-treat analysis, the eradication rate was 91.6% (95% confidence interval (CI), 85.5-95.7%). For the per-protocol analysis, the eradication rate was 94.5% (95% CI, 89-97.8%). Adverse events were noted in 42 of 131 (32.1%); drug compliance was excellent with 96.9% of the patients taking more than 90% of the prescribed medication. A 10-day concomitant regimen appears to be an effective, safe, and well-tolerated treatment option for first-line H. pylori eradication in Greece.


Prolonged diapause in the ectoparasite Carnus hemapterus (Diptera: Cyclorrhapha, Acalyptratae) - how frequent is it in parasites?
Prolonged diapause is usually interpreted as an adaptation to unpredictable environmental conditions and resource availability. Many parasites usually face highly unpredictable environments, therefore prolonged diapause should be common among these organisms. Here we examine the occurrence and frequency of prolonged diapause in the ectoparasite Carnus hemapterus (Diptera: Cyclorrhapha, Acalyptratae). We found that the studied population is polymorphic with respect to diapause duration. Emergence of carnid flies after 2 and 3 wintering seasons was therefore detected in around 17% and 21% of the samples respectively. The number of flies with prolonged diapause ranked 0.88-50% with respect to the number of flies emerging during the first spring. Both the occurrence of prolonged diapause and the number of flies with a long life-cycle are related to the number of flies emerging during the first spring. The emergence pattern of flies with prolonged diapause was very similar to that observed for flies with a short cycle and occurred in synchrony with the occurrence of hosts. Prolonged diapause has been frequently reported in plant-feeding insects and in some host-parasitoid systems, but this is, to our knowledge, the second report ever on prolonged diapause in true parasites of animals. We discuss the reasons for the apparent rarity of prolonged diapause among these organisms.


The contribution of occupational factors on frailty.
Frailty is a clinical condition characterized by enhanced vulnerability to stressors and increased risk of developing dependency and/or mortality. It has been described as the multidimensional and dynamic condition that cannot be easily disentangled from psychosocial determinants. To date, the possible role of occupational factors on frailty development and its progression at advanced age are not yet fully understood. The aim of this work is to provide a comprehensive overview of existing evidence exploring the relationship between multiple occupational issues (e.g., employment history, workplace risk factors, organizational job characteristics) and frailty. A systematic search and revision of available literature addressing the contribution of occupational factors on the quantitative and qualitative aspects of frailty in the elderly was performed in the Pubmed, Scopus, and ISI Web of Science databases. The major weaknesses of existing literature reside in the heterogeneous operationalization of frailty and the limited description of the workplace factors. Nevertheless, an association between life-course occupational conditions and frailty was documented. In particular, intrinsically harder, manual, or blue-collar occupations emerged as possible determinants of the frailty manifestation and severity at older age. Our preliminary results do not allow extrapolating definite conclusions. Further studies are needed. However, it seems that a significant relationship exists between the life-course occupation and frailty at advanced age. From a public health and social geriatric perspective, this work may provide the basis to define future innovations for preventing frailty at elderly adopting a life-course approach.


Replication of IFDO on a chemically defined medium.
An agar or liquid medium containing haemoglobin, high density horse lipoprotein, trypsin, Tween 80, phosphate buffer, CaCl(2), glucose, glutamic acid and NaCl supported growth of ileal fluid dependent organism (IFDO). Glucose, glutamic acid and NaCl were not essential but enhanced growth. Trace amounts of lipoprotein were sufficient to support growth, and some human sera and serum fractions rich in low density lipoprotein could be substituted for horse lipoprotein. Addition of lipase enhanced the growth rate, and reduced the requirement for lipoprotein. No nucleic acid precursors were identified as essential for growth. However, nucleosides, especially cytidine, accelerated the growth rate. The growth rate was also increased by DNAase and RNAase. These observations indicate that the organisation of the IFDO particle is more complex than that of a crystal. They are consistent with the hypothesis that IFDO is a replicating agent that utilises specific preformed protein to assemble a proteinaceous particle, and support the postulated relationship of IFDO to transmissible spongiform encephalopathy agents.


Only skin deep: optimism and public self-consciousness did not associate with the placebo response in a dermatology clinical trial.
Although not well-understood, dermatologic diseases studied in clinical trials often demonstrate substantial response to placebo. The study objective is to determine if optimism, public self-consciousness and other personality traits predict response to placebo or active treatment in a dermatology clinical trial. A questionnaire was mailed to subjects previously enrolled in a two-center rosacea study who had been randomized to either a treatment or placebo gel. The questionnaire included the Revised Life Orientation Test (LOT-R), the Public Self-Consciousness Scale, and questions to assess personality traits. Forty-seven subjects out of 83 (57%) returned the questionnaire. There was no statistically significant difference in the LOT-R score in those who responded to placebo versus those who did not (18.08 vs 17.92, P =0.92) nor in those who responded to active treatment versus those who did not (16.27 vs 15.86, P =0.79). There was no statistically sigificant difference in public-self consciousness among placebo or active treatment responders versus non-responders (11.75 vs 10.67, P =0.66; 13.55 vs 14.45, P =0.68). The placebo responders were more likely to report that they were not unusually sensitive to most drugs/medications (X2= 8.33, P =0.004). Although this pilot study is small, there was no meaningful difference in levels of optimism or public self-consciousness among those who responded to placebo. Placebo responders were more likely to report that they were not sensitive to most drugs/medications, raising the possibility that they are actually less likely to detect when they are on medications.


Expression, purification, and biochemical characterization of Chk, a soluble protein tyrosine kinase.
CSK family contains two protein tyrosine kinases: Csk (C-terminal Src kinase) and Chk (Csk homologous kinase). They are responsible for phosphorylating Src family protein tyrosine kinases on a C-terminal Tyr (Tyr527) and negatively regulating their activities. However, Chk and Csk have different expression patterns, mechanisms of regulation, and different biological functions, and appear to play different roles in the development of breast cancer. To obtain pure human Chk for biochemical characterization, its coding region was amplified by polymerase chain reaction and expressed as a fusion protein with glutathione S-transferase in Escherichia coli. The enzyme was highly expressed but unusually prone to proteolytic degradation during purification. Expression of the enzyme as a dual fusion protein with glutathione S-transferase on N-terminus and streptag, a 10 amino acid peptide, on C-terminus allowed purification of the full-length fusion protein. The purified enzyme was able to phosphorylate and inactivate Src. Chk (no inhibition up to 18.5 microM) and Csk (IC(50)= 1 microM) were differentially inhibited by PP2, probably due to the size difference of one residue (Thr265 in Csk versus Met304 in Chk) in the ATP-binding domain. The expression, purification, and initial characterizations of Chk provided an important step toward full characterization of Chk and Csk, two important enzymes in cellular regulation.


Comparison of efficiency and preference of metal and plastic spacers in preschool children.
The metal NebuChamber valved holding chamber (VHC) has gained wide acceptance among children with asthma. Due to its nonelectrostatic properties and larger volume, the 250-mL, metal NebuChamber delivers a greater mass of aerosol to a filter at the mouth compared with the commonly used 150-mL polypropylene AeroChamber VHC. Such in vitro results have been used to suggest that this may provide increased efficacy with the NebuChamber. No comparative efficacy data exist for preschool children with asthma. To compare efficiency and preference of metal and plastic spacers in preschool children. Children with mild-to-moderate persistent asthma received 200 microg of budesonide twice daily by NebuChamber or AeroChamber, both with the mask provided in a randomized, 2-month, crossover trial. Symptom diary cards, beta-agonist use, and preference by children and parents were compared. Thirty children (mean +/- SD age, 4.3 +/- 0.3 years) completed the study. There was no difference between the AeroChamber and NebuChamber in clinical efficacy outcomes. There was no difference between the AeroChamber and NebuChamber in parents' view of ease of use, design, acceptability by the children, and overall satisfaction. Despite a greater total dose delivered to the mouth, the NebuChamber appears no more effective than the AeroChamber and it is not preferred by patients or parents. More parents chose to continue to use the NebuChamber after the study.


The hMsh2-hMsh6 complex acts in concert with monoubiquitinated PCNA and Pol η in response to oxidative DNA damage in human cells.
Posttranslational modification of PCNA by ubiquitin plays an important role in coordinating the processes of DNA damage tolerance during DNA replication. The monoubiquitination of PCNA was shown to facilitate the switch between the replicative DNA polymerase with the low-fidelity polymerase eta (η) to bypass UV-induced DNA lesions during replication. Here, we show that in response to oxidative stress, PCNA becomes transiently monoubiquitinated in an S phase- and USP1-independent manner. Moreover, Polη interacts with mUb-PCNA at sites of oxidative DNA damage via its PCNA-binding and ubiquitin-binding motifs. Strikingly, while functional base excision repair is not required for this modification of PCNA or Polη recruitment to chromatin, the presence of hMsh2-hMsh6 is indispensable. Our findings highlight an alternative pathway in response to oxidative DNA damage that may coordinate the removal of oxidatively induced clustered DNA lesions and could explain the high levels of oxidized DNA lesions in MSH2-deficient cells.


A Systematic Review of the Symptom Profile and Course of Methamphetamine-Associated PsychosisSubstance Use and Misuse.
The psychiatric symptom profile of methamphetamine-associated psychosis (MAP) has varied considerably across studies of different research designs. We performed a systematic review to examine the available evidence for specific psychotic symptoms associated with MAP, including the clinical course and longitudinal changes in this symptom profile. Five key electronic databases were searched to identify studies that examined the symptom profile or clinical course of MAP in individuals identified as having MAP. The reporting of specific psychiatric symptoms, and duration of symptoms where available, was recorded for each study. Ninety-four articles were identified (n = 7387), including case-control (k = 29), cross-sectional (k = 20), experimental (k = 6), case report (k = 29), and longitudinal (k = 20) studies. Persecutory delusions, auditory and visual auditory hallucinations were by far the most commonly reported symptoms (reported in 65-84% of studies). Hostility, conceptual disorganization, and depression were reported in a large proportion of studies (31-53%). Negative symptoms were mostly absent (<20%). The median percentage of participants with persistent psychotic symptoms (>1 month duration) across studies was 25% (excluding case reports). Persecutory delusions, auditory and visual hallucinations, hostility, depression and conceptual disorganization are central to MAP, whereas negative psychotic symptoms are typically absent. An overrepresentation of institutionalized or male participants may have overemphasized negative symptoms and underreported affective symptoms in past research. Symptoms of MAP may persist beyond one month after drug cessation in some individuals. Clinicians are encouraged to manage affective symptoms in MAP individuals, and monitor for the development of chronic psychotic symptoms.


Left atrial myxoma on FDG-PET/CT.
A 56-year-old woman with rheumatoid factor-positive rheumatoid arthritis underwent FDG-PET/CT because of fatigue, fever, coughing, and weight loss for several months. FDG-PET/CT solely revealed a mildly hypermetabolic hypodense area in the left atrium. Subsequently, transthoracic echocardiography and contrast-enhanced MRI showed a left atrial pedunculated soft tissue mass suggestive for myxoma, with histological confirmation. Myocardial involvement by tumors is rare, and FDG-PET/CT has been very useful for identifying cardiac metastases. However, very few cases have been reported using FDG-PET/CT for detecting primary cardiac tumors, but as shown here, abnormal focal myocardial uptake should trigger further morphological assessment.


Genetic polymorphism of metallothionein 2A and risk of laryngeal cancer in a Polish population.
Metallothioneins are intracellular regulators of many biological mechanisms including differentiation, proliferation, angiogenesis and invasion, which are crucial processes in carcinogenesis. This study examines the association between three single-nucleotide polymorphisms at loci -5 A/G (rs28366003) and -209 A/G (rs1610216) in the core promoter region and at locus +838 C/G (rs10636) in 3'UTR region of the metallothionein 2A (MT2A) gene with squamous cell laryngeal cancer (SCLC) risk, as well as with tumor invasiveness according to tumor front grading (TFG). Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism technique in 323 genetically unrelated individuals with SCLC and 418 randomly selected healthy volunteers. Only one SNP (rs28366003) was significantly related to laryngeal cancer in the study population. Compared with homozygous common allele carriers, heterozygous and homozygous for the G variant had significantly increased risk of SCLC [adjusted odds ratio (OR) = 2.90, 95 % confidence interval (CI) 1.53-5.21, p dominant < 0.001]. The A/G allele carriers at rs28366003 MT2A were at higher risk of SCLC development (OR = 2.63, 95 % CI 1.41-2.85, p < 0.001]. There was a significant association between the rs28366003 and stage and TFG classification. Most carriers of minor allele had a higher stage (OR = 2.76, 95 % CI 1.11-7.52, p = 0.03), increased cancer aggressiveness, as defined by a higher total TFG score (>18 points) (OR = 3.76, 95 % CI 1.15-12.56, p = 0.03) and diffuse tumor growth (OR = 5.86, 95 % Cl 0.72-44.79, p = 0.08). The results of this study raise a possibility that a genetic variation of MT2A may be implicated in the etiology of laryngeal cancer in a Polish population.


Enhancing nitrite reductase activity of modified hemoglobin: bis-tetramers and their PEGylated derivatives.
The clinical evaluation of stabilized tetrameric hemoglobin as alternatives to red cells revealed that the materials caused significant increases in blood pressure and related problems and this was attributed to the scavenging of nitric oxide and extravasation. The search for materials with reduced vasoactivity led to the report that conjugates of hemoglobin tetramers and polyethylene glycol (PEG) chains did not elicit these pressor effects. However, this material does not deliver oxygen efficiently due to its lack of cooperativity and high oxygen affinity, making it unsuitable as an oxygen carrier. It has been recently reported that PEG-conjugated hemoglobin converts nitrite to nitric oxide at a faster rate than does the native protein, which may compensate for the scavenging of nitric oxide. It is therefore important to alter hemoglobin in order to enhance nitrite reductase activity while retaining its ability to deliver oxygen. If the beneficial effect of PEG is associated with the increased size reducing extravasation, this can also be achieved by coupling cross-linked tetramers to one another, giving materials with appropriate oxygen affinity and cooperativity for use as circulating oxygen carriers. In the present study it is shown that cross-linked bis-tetramers with good oxygen delivery potential have enhanced nitrite reductase activity with k(obs) = 0.70 M(-1) s(-1) (24 degrees C), compared to native protein and cross-linked tetramers, k(obs) = 0.25 M(-1) s(-1) and k(obs) = 0.52 M(-1) s(-1), respectively, but are less active in reduction of nitrite than Hb-PEG5K(2) (k(obs) = 2.5 M(-1) s(-1)). However, conjugation of four PEG chains to the bis-tetramer (at each beta-Cys-93) produces a material with greatly increased nitrite reductase activity (k(obs) = 1.8 M(-1) s(-1)) while retaining cooperativity (P(50) = 4.1, n(50) = 2.4). Thus, PEGylated bis-tetramers combine increased size and enhanced nitrite reductase activity expected for decreased vasoactivity with characteristics of an acceptable HBOC.


The early historical roots of pediatric and adolescent gynecology.
The science of medicine is a constantly evolving process that builds on the experiences and observations of the past. We hypothesized that the issues of pediatric and adolescent gynecology were also of concern to physicians practicing in the 19th century. We sought to determine the extent to which our forebears of over 100 years ago considered, diagnosed, and treated these problems. We conducted an exhaustive search through two English-language medical journals, The Obstetrical Journal of Great Britain and Ireland (vol. 1-7, 1873-1880) and The American Journal of Obstetrics (vol. 1-32, 1869-1895), for articles relating to pediatric and adolescent gynecology. The most frequently encountered subject was the surgical management of congenital absence or atresia of the vagina and associated anomalies of adjacent organs. By 1881, the opinion expressed by many investigators was that the method used by Thomas Addis Emmet to create an artificial vagina between the bladder and the rectum by a single-stage procedure of blunt dissection and the immediate placement of a glass vaginal dilator gave the best chance of a favorable outcome. The practice of making an artificial opening through the rectum was abandoned. In 1882, a review of published reports noted 43% postoperative mortality in children treated for benign and malignant ovarian tumors. A review article in 1891 reported a 10% mortality rate associated with treatment of the imperforate hymen. A research article in 1870 noted the mean age at menarche in England to be 14.96 years. Additional subjects in the literature included: "Acquired Venereal Disease in Children" warning of the need for "rigid ... scrutiny of the attendants and playmates of children" (1893), the enigmatic occurrence of "Vaginal Hemorrhage in an Infant Five-Days-Old" (1874), the brutal atrocities perpetrated against "The Child Wives of India" (1895), "Early Pregnancy" reviewing childbirth by young adolescents (1874), "Hermaphrodism" (1886), "The ... Hymen and Its Remains ..." (1871), a "Case of Fatal Hemorrhage from the Genital Organs" in which a 17-year-old exsanguinated from a vaginal laceration (1879), and "Primary Sarcoma of the Vagina ... in a Child Three-Years-Old" (1881). Modern pediatric and adolescent gynecology can trace its roots to well over a century ago.


The effect of a short educational intervention on the use of urinary catheters: a prospective cohort study.
To assess the effectiveness of implementation of evidence-based recommendations to reduce catheter-associated urinary tract infections (CAUTIs). Prospective cohort study, conducted in 2010-12, with a before and after design. A major referral university hospital. Data were collected before (n = 244) and 1 year after (n = 255) the intervention for patients who received urinary catheters. The intervention comprised two elements: (i) aligning doctors' and nurses' knowledge of indications for the use of catheters and (ii) an educational effort consisting of three 30- to 45-minute sessions on evidence-based practice regarding catheter usage for nursing personnel on 17 medical and surgical wards. The main outcome measures were the proportion of (i) admitted patients receiving urinary catheters during hospitalization, (ii) catheters inserted without indication, (iii) inpatient days with catheter and (iv) the incidence of CAUTIs per 1000 catheter days. Secondary outcome measures were the proportion of (i) catheter days without appropriate indication and (ii) patients discharged with a catheter. There was a reduction in the proportion of inpatient days with a catheter, from 44% to 41% (P = 0.006). There was also a reduction in the proportion of catheter days without appropriate indication (P < 0.001) and patients discharged with a catheter (P = 0.029). The majority of catheters were inserted outside the study wards. A short educational intervention was feasible and resulted in significant practice improvements in catheter usage but no reduction of CAUTIs. Other measures than CAUTI may be more sensitive to detecting important practice changes.


Home hemodialysis in Australia and New Zealand: practical problems and solutions.
Home hemodialysis, as practiced in Australia and New Zealand, offers patients the return of self-control and self-esteem. It also allows reconnection with family, friends and (re)employment. Though there are emotional and time-related "costs" with home hemodialysis, these center on training time, commitment and patient or family stresses and, if carefully managed and properly resourced, can be overcome for most home-suitable patients. As we believe many center-based hemodialysis patients are home-suitable and that home care is severely under-utilized, assessment techniques to maximize uptake are examined. While patient dropout from home care relates more to staff attitudes than to true home-failure, dropout is minimized by ensuring the patient and not a carer takes full dialysis responsibility with the carer acting as a supporter and not the facilitator. Installation of home equipment is simple and cheap, the financial costs of home hemodialysis being substantially less than those of facility care where salary and infrastructure costs far exceed training, equipment, installation and maintenance costs at home. Home monitoring is not routinely required especially with longer, more frequent regimens-but effective 24-hour on-call nurse and technician cover is essential. Intravenous drug self-administration at home is safe and effective, reducing the need for hospital visits to a 2-3 monthly minimum. The debilitating effects of facility care cannot be over-emphasized while the liberating psychology of a well-supported hemodialysis program is truly satisfying for patient and staff alike.


Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study).
Children with allergic rhinitis are likely to develop asthma. The purpose of this investigation was to determine whether specific immunotherapy can prevent the development of asthma and reduce bronchial hyperresponsiveness in children with seasonal allergic rhinoconjunctivitis. From 6 pediatric allergy centers, 205 children aged 6 to 14 years (mean age, 10.7 years) with grass and/or birch pollen allergy but without any other clinically important allergy were randomized either to receive specific immunotherapy for 3 years or to an open control group. All subjects had moderate to severe hay fever symptoms, but at inclusion none reported asthma with need of daily treatment. Symptomatic treatment was limited to loratadine, levocabastine, sodium cromoglycate, and nasal budesonide. Asthma was evaluated clinically and by peak flow. Methacholine bronchial provocation tests were carried out during the season(s) and during the winter. Before the start of immunotherapy, 20% of the children had mild asthma symptoms during the pollen season(s). Among those without asthma, the actively treated children had significantly fewer asthma symptoms after 3 years as evaluated by clinical diagnosis (odds ratio, 2.52; P <.05). Methacholine bronchial provocation test results improved significant in the active group (P <.05). Immunotherapy can reduce the development of asthma in children with seasonal rhinoconjunctivitis.


Effect of pegylation on the structure and function of horse cytochrome c.
The preparation and spectrophotometric characterization of (both Fe2+ and Fe3+ forms) poly(ethylene glycol) (PEG; av FW 5000)-modified horse cytochrome c (cyt c(PEG)n) with different degrees of modification (nav = 6, 19) by UV-vis spectroscopy, circular dichroism spectroscopy, resonance Raman spectroscopy, and cyclic voltammetry are described. Extensive modification (nav = 19) of cyt c causes gross structural deformation of the heme as evidenced by major spectral changes in the UV-vis and circular dichroism spectral signatures of both the Fe2+ and Fe3+ forms. Modification of cyt c by six PEG residues, however, produces a protein in which the heme active site is structurally and functionally intact (UV-vis, circular dichroism, and resonance Raman) and which exhibits at least quasireversible direct electron transfer (Eo' = 338 +/- 5 mV vs SHE; (2.1 +/- 0.6) x 10(-3) cm/s) at bis(4-pyridyl) disulfide-modified Au electrodes.


Management of tooth surface loss.
This part of the series is devoted to tooth surface loss (TSL) not caused by caries or trauma. The management of this form of generalised TSL is included in this series because knowledge of occlusion is needed for both the diagnosis and, when indicated, treatment. There are, however, many other factors involved in the management of generalised TSL other than those associated with 'occlusion'. These will also be discussed.


[Synthetic inhibitors of serine proteinases. 31. The inhibition of trypsin, plasmin and thrombin by isomeric compounds of N alpha -arylsulfonylated omega-amidinophenyl-alpha-aminoalkylcarboxylic acid amides].
Isomeric compounds of N alpha-arylsulfonylated amides of omega-amidinophenyl-alpha-aminoalkylcarboxylic acids--N alpha-amidinophenylsulfonylated amides or N alpha-arylsulfonylated amidino anilides of omega-phenyl-alpha-aminoalkylcarboxylic acids, respectively--possess weak antithrombin activity as compared to the derivatives of the basic structure. Thus, the assumption is corroborated that specific enzyme-inhibitor interactions account for the high antithrombin activity of certain derivatives of omega-amidinophenyl-alpha-aminoalkylcarboxylic acids. In contrast, amidinoanilides of N alpha-substituted omega-phenyl-alpha-aminoalkylcarboxylic acids are potent inhibitors of trypsin and plasmin, their inhibitory activity approaches that of primary amides of N alpha-substituted omega-amidinophenyl-alpha-aminoalkylcarboxylic acids.


Comparison of charged nanoparticle concentrations near busy roads and overhead high-voltage power lines.
Overhead high-voltage power lines are known sources of corona ions. These ions rapidly attach to aerosols to form charged particles in the environment. Although the effect of ions and charged particles on human health is largely unknown, much attention has focused on the increasing exposure as a result of the expanding power network in urban residential areas. However, it is not widely known that a large number of charged particles in urban environments originate from motor vehicle emissions. In this study, for the first time, we compare the concentrations of charged nanoparticles near busy roads and overhead power lines. We show that large concentrations of both positive and negative charged nanoparticles are present near busy roadways and that these concentrations commonly exceed those under high-voltage power lines. We estimate that the concentration of charged nanoparticles found near two freeways carrying around 120 vehicles per minute exceeded the corresponding maximum concentrations under two corona-emitting overhead power lines by as much as a factor of 5. The difference was most pronounced when a significant fraction of traffic consisted of heavy-duty diesel vehicles which typically have high particle and charge emission rates.


Expression of prolyl-hydroxylase-1 (PHD1/EGLN2) suppresses hypoxia inducible factor-1alpha activation and inhibits tumor growth.
Hypoxic stress is one of the major selective pressures in the microenvironment of solid tumors, and overcoming this restriction is essential for tumor progression. One of the key factors driving the cellular response to lack of oxygen is hypoxia inducible factor (HIF), a key transcriptional factor. The level of the alpha subunit of HIF-1 is regulated by rapid degradation that is controlled by a family of prolyl hydroxylases (PHDs/EGLNs), the activity of which depends on oxygen availability. Our study shows that ectopic expression of mPHD1 suppressed accumulation of HIF-1alpha and secretion of Vascular Endothelial Growth Factor after treatment of cells with a hypoxia-mimetic drug. Furthermore, when colon carcinoma cells expressing mPHD1 were injected into nude mice, tumor growth was inhibited, and the inhibition of tumor growth was correlated with increased necrosis and a striking decrease in microvessel density. These data demonstrate that inhibition of hypoxia-induced activation of HIF-1alpha through activation of HIF-hydroxylase can provide a novel therapeutic strategy for inhibition of tumor growth and neovascularization and support the development of gene transfer approaches based on the activation of HIF-prolyl hydroxylases.


Increased risk of second primary hematologic and solid malignancies in patients with mycosis fungoides: A Surveillance, Epidemiology, and End Results analysis.
Mycosis fungoides (MF) is associated with increased risk of second primary hematologic malignancies, but its association with second primary solid tumors is less well characterized. This retrospective analysis seeks to assess the risk of being diagnosed with a second primary hematologic or solid malignancy in patients with MF. We performed an analysis of patients diagnosed with MF from 2000 through 2015 in the United States cancer registries of SEER-18 (N = 6742). Relative risks were estimated by using standardized incidence ratios (SIRs). Among 6742 patients, there were 511 (7.5%) second cancer events (SIR, 10.15; 95% confidence interval [CI], 9.29-11.07). These included 184 (36.0%) hematologic malignancies (SIR, 39.71; 95% CI, 34.05-46.05) and 327 (64.0%) solid tumor malignancies (SIR, 7.33; 95% CI, 6.56-8.17). Patients with MF were at increased risk for non-Hodgkin lymphoma; Hodgkin lymphoma; melanoma; and lung, female breast, prostate, colon, and renal cancers. Females were at higher risk than males (P < .05). All ethnic groups showed a statistically significant elevation in SIRs. Elevation of SIRs was observed across all stages of MF. Patients with MF are at increased risk for diagnosis of second primary malignancies and should be carefully screened for discernable signs and symptoms of second malignancies.


'Yes!--a chance to tell my side of the story': a case study of a male partner of a woman undergoing termination of pregnancy for foetal abnormality.
Interpretative phenomenological analysis (IPA) was used to analyse data from one man whose partner underwent a third-trimester termination of pregnancy for foetal abnormality. This case study examines the data from the participant and aspects of grief are examined qualitatively from a male perspective. The importance of the male role, management of his own particular needs and coping mechanisms are discussed in the context of society's expectations and current thinking on grief counselling. The impact of a new technique in obstetric management is highlighted in this case.


T-cell depletion by monoclonal antibodies does not prevent granuloma formation in mice.
Effects of T-cell depletion on the formation of organized granulomas in mouse skin were investigated. Monoclonal antibodies (MoAbs) to L3T4 and Lyt-2.2 were injected into euthymic BALB/c mice in order to deplete both T-helper and T-suppressor cell populations. Four days after injection, hepatic schistosome egg granulomas were transplanted into the skin. Injection of MoAbs to L3T4 and Lyt-2.2 was repeated in the recipient mice 6 days later. At the time of transplantation, flow cytometric analysis showed that the number of T cells which were positively stained with surface markers decreased on average by 68% in both regional lymph nodes and spleen. The mitogen response of spleen cells was also markedly reduced. Despite their immunosuppressed condition, development of organized granulomas was observed in the skin of recipient mice by light and electron microscopy 3 weeks after transplantation. The findings indicate that T-cell function may not be essential for initiation of organized granuloma formation.


Cytopathologic changes associated with intrauterine contraceptive devices. A review of cervico-vaginal smears in 350 women.
Cervico-vaginal smears from 350 IUCD users were analysed to ascertain the range of abnormalities induced in the genital tract of these women. Alteration of the microbial environment, inflammatory, degenerative, reparative and proplastic epithelial changes were the salient cytological findings. The clinical implications of these are briefly discussed.


[Facts and figures of clinical pathways in Italy: results from the PDTA Net project.]
The approval of clinical pathways (CPWs) represents a key step to focus the care management on the patient. The PDTA Net project, by ReS Foundation and CINECA, aims to create a reference tool to study how the local organizational models influence healthcare and clinical outcomes. The article shows the analysis of all CPWs approved by Italian Regions and Autonomous Provinces until 31/12/2018. The search for documents was performed on the institutional websites through specific keywords. CPWs were filled into a database, according to the Region, publication year, disease of interest (distinguishing between chronic diseases with high epidemiological impact and rare diseases) and relevant clinical area. All documents were analyzed by geographical and temporal distribution, the latter also according to ministerial measures. From 2005 to 2018, 536 Regional CPWs were approved (316 for chronic diseases with a high epidemiological impact and 220 for rare diseases). The Regions with the highest number of CPWs of chronic diseases were Umbria (34 CPWs) and Piemonte (33). The most addressed clinical areas were: oncology (72), neurology (60), cardiology (34) and metabolic disorders (22). The most issued diseases were: diabetes (17), trauma/polytrauma (15), chronic obstructive pulmonary disease and multiple sclerosis (12 each), stroke (11), rheumatoid arthritis, breast cancer and colorectal neoplasms (10 each). The publication of the documents was affected by ministerial measures (Balduzzi Law, National Chronicity Plan, Diabetic Disease Plan and National Dementia Plan). The majority of CPWs on rare diseases was retrieved in Regions with activated Rare Disease Networks: Lombardia (110 CPWs), Lazio (64) and Toscana (17). This study showed that, to date, in Italy there are several CPWs published at Regional level, nevertheless their structure and application are heterogeneous and strongly influenced by the National Plans. All analyzed documents are available through the web platform of the project https://fondazioneres.it/pdta/. This project could be useful for health system stakeholders, in order to encourage the transition to new health governance and making CPWs effective governance tools.


Expression of Fos in the superior lateral subdivision of the lateral parabrachial (LPBsl) area after generalized tonic seizures in rats.
Generalized tonic-clonic seizures of brain stem origin in rats are associated with acute induction of neuronal Fos in several discrete regions of the brain. One particular site in the dorsal pons shows remarkable Fos induction following generalized tonic seizures induced by maximal electroshock in normal rats or by audiogenic stimulation in genetically epilepsy-prone rats (GEPRs). Although this area shows the most intense Fos induction of any brain area following generalized tonic seizures, its identity has been uncertain. Based on its general location, we hypothesized that this nucleus was either 1) a component of the pedunculopontine tegmentum nucleus-pars compacta (PPTn-pc) or 2) the superior lateral subnucleus of lateral parabrachial area (LPBsl). The present study used Fos-protein immunocytochemistry in combination with the reduced form of nicotinamide-adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry, cholecystokinin (CCK) immunocytochemistry, and neuronal tract-tracing to determine the identity of this cluster of Fos-immunoreactive neurons in the dorsal pons. Following maximal electroshock seizure (MES), Fos labeling was compared to NADPH diaphorase staining (a marker for cholinergic neurons of the PPTn-pc); retrograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injected into the ventromedial nucleus of the hypothalamus (VMH; to identify the LPBsl) or CCK immunoreactivity (also a marker for LPBsl neurons). Results showed this cluster of Fos immunoreactive (FI) neurons to be closely associated, but not overlapping, with the lateral and most caudal aspect of the PPTn-pc. Alternatively, WGA-HRP retrograde-labeled neurons corresponded precisely with the seizure-induced FI neurons. Additionally, the location of CCK immunoreactive neurons directly overlapped with the FI neurons, although they were not nearly as prevalent. These results demonstrate that the seizure-induced FI neurons in this area are neurons of the LPBsl and not cholinergic neurons of the PPTn-pc. This is the first report of seizure-induced Fos expression specifically localized to the superior lateral subnucleus of the lateral parabrachial area.


Metabolism of inositol-1,4,5-trisphosphate in the taste organ of the channel catfish, Ictalurus punctatus.
1. The metabolism of inositol-1,4,5-trisphosphate was studied in the taste organ (barbel) of the channel catfish, Ictalurus punctatus. 2. Homogenates of epithelial barbel scrapings were incubated with [3H]-1,4,5-IP3, whose dephosphorylation or phosphorylation was assayed under first-order conditions by measuring the production of either [3H]-1,4-IP2 (representing the activity of IP3-5-phosphatase) or [3H]-1,3,4,5-IP4 (representing the activity of IP3-3-kinase). 3. Both enzymes were predominantly cytosolic, magnesium-dependent and maximally active at pH 6.4. For IP3-phosphatase, Km = 6 microM and Vmax = 10.5 nmol/min/mg. For IP3-kinase, Km = 0.23 microM and Vmax = 0.05 nmol/min/mg. 4. Neither enzyme was significantly affected by the presence of taste stimuli (amino acids), GTP gamma S, cAMP or phorbol esters. 5. In the presence of physiological levels of free calcium (0.05-12 microM) IP3-phosphatase was moderately activated whereas IP3-kinase was moderately inhibited. 6. IP3-phosphatase was moderately activated by Mn2+, unaffected by LiCl, and strongly inhibited by 2,3-diphosphoglycerate, Na-pyrophosphate, CdCl2, HgCl2, CuCl2, FeCl3 and ZnSO4 7. IP3-kinase was strongly activated by 2,3-diphosphoglycerate, Na-pyrophosphate, CdCl2, HgCl2, FeCl3 and LiCl and inhibited by ZnSO4 and Mn2+. 8. IP3-kinase was significantly activated in a calcium-dependent manner by exogenously-added phosphatidylcholine and sphingomyelin, and to a lesser extent by diacylglycerol. IP3-phosphatase was unaffected by exogenously-added lipids. 9. IP3-phosphatase may participate in taste transduction since calculations based on the first-order rate constant (6.9 sec-1) indicate that it is capable of dephosphorylating basal levels of IP3 with a half-life of 0.1 sec.


Bias in relative odds estimation owing to imprecise measurement of correlated exposures.
A series of graphs is presented that show the estimated degree of bias in logistic coefficient estimates for two correlated continuous exposures measured with imprecision. These graphs indicate that even when the correlation coefficient between the exposure of interest and a correlated exposure is as low as 0.2, imprecision in the measurement of the latter exposure can result in at least as serious bias in the logistic coefficient estimate for the exposure of interest as measurement imprecision in the exposure of interest itself. The implications for the design and interpretation of epidemiological studies are discussed.


[Diagnostic value of Frank's corrected orthogonal electrocardiogram].
The changes in the corrected orthogonal electrocardiograms of 411 patients were analyzed: 134 with right ventricle loading, 137 with left ventricle loading and 140 with myocardial infarction (chronic phase). On the base of sensitivity and specificity criteria the indices SXmV, SXmsec and QZmV for the patients with right ventricle loading and RXmV and RZmV for the patients with left ventricle loading proved to be with the highest diagnostic value. Sensitivity is within 19% to 61%. Sensitivity is within 85% and 95% in patients with myocardial infarction (chronic phase), for the different indices depending on the infarction zone. The comparative analyses of the indices of the corrected orthagonal Frank electrocardiogram and the standard electrocardiogram (12 leads) give a certain preference to the indices of the standard electrocardiography.


Can You Multitask? Evidence and Limitations of Task Switching and Multitasking in Emergency Medicine.
Emergency physicians work in a fast-paced environment that is characterized by frequent interruptions and the expectation that they will perform multiple tasks efficiently and without error while maintaining oversight of the entire emergency department. However, there is a lack of definition and understanding of the behaviors that constitute effective task switching and multitasking, as well as how to improve these skills. This article reviews the literature on task switching and multitasking in a variety of disciplines-including cognitive science, human factors engineering, business, and medicine-to define and describe the successful performance of task switching and multitasking in emergency medicine. Multitasking, defined as the performance of two tasks simultaneously, is not possible except when behaviors become completely automatic; instead, physicians rapidly switch between small tasks. This task switching causes disruption in the primary task and may contribute to error. A framework is described to enhance the understanding and practice of these behaviors.


Preclinical Studies on Biomaterial Scaffold use in Knee Ligament Regeneration: A Systematic Review.
Knee joint trauma may result in damage of the intra-articular ligaments, with rupture of the anterior cruciate ligament (ACL) a common and troublesome injury due to poor capabilities for spontaneous regeneration. Autograft and allograft surgical reconstructions are the mainstay of treatment, but have associated risks of failure, therefore tissue-engineering techniques aiming to regenerate the native ACL are being researched as a potential alternative treatment. This article aims to review the current evidence produced by ex vivo and in vivo studies investigating biomaterial scaffolding and mesenchymal stem cell (MSC) techniques in orthopaedic tissue engineering of ACL injuries. Databases searched were Ovid MEDLINE, Cochrane Library, Embase, Elsevier Scopus, Web of Science and NCBI PubMed, with search terms 'ligament', 'scaffold', 'mesenchymal stem cell' and 'tissue engineering'. 1132 articles were identified, with 19 articles suitable for review inclusion. Of the eligible studies, 10 used biologic scaffold material, 6 used synthetic constructs, and hybrid scaffolds were employed in the remaining 3 studies. A large amount of preclinical evidence for viability of MSC seeded biomaterial scaffolds in ACL regeneration exists. Studies show that with stimulation, MSCs adhere and proliferate well on various scaffold materials ranging from silk to engineered polymers. Hybrid scaffolds are particularly promising, and with further research, the best features from strong natural substances such as silk, and biologically inert synthetic materials could be combined. Currently, there are few plans to begin human clinical trials, but preclinical studies are moving into larger animal models.


Training and outcome monitoring in robotic urologic surgery.
The use of robot-assisted laparoscopic technology is rapidly expanding, with applicability in numerous disciplines of surgery. Training to perform robot-assisted laparoscopic urological procedures requires a motivated learner, a motivated teacher or proctor, a curriculum with stepwise learning objectives, and regular access to a training robot. In light of the many constraints that limit surgical training, animal models should be utilized to quantifiably improve the surgical skills of residents and surgical fellows, before these skills are put into practice on patients. A system based on appropriate supervision, graduated responsibility, real-time feedback, and objective measure of progress has proven to be safe and effective. Surgical team education directed towards cohesion is perhaps the most important aspect of training. At present, there are very few published guidelines for the safe introduction of robotic urologic surgery at an institution. Increasing evidence demonstrates the effects of learning curve and surgical volume on oncological and functional outcomes in robotic surgery (RS). This necessitates the introduction of mechanisms and guidelines by which trainee surgeons can attain a sufficient level of skill, without compromising the safety of patients. Guidelines for outcome monitoring following RS should be developed, to ensure patient safety and sufficient baseline surgeon skill.


The impact of preparation parameters on typical attributes of chitosan-heparin nanohydrogels: particle size, loading efficiency, and drug release.
Today, developing an optimized nanoparticle (NP) preparation procedure is of paramount importance in all nanoparticulate drug delivery researches, leading to expanding more operative and clinically validated nanomedicines. In this study, a one-at-a-time experimental approach was used for evaluating the effect of various preparation factors on size, loading, and drug release of hydrogel NPs prepared with ionotropic gelation between heparin and chitosan. The size, loading efficiency (LE) and drug release profile of the NPs were evaluated when the chitosan molecular weight, chitosan concentration, heparin addition time to chitosan solution, heparin concentration, pH value of chitosan solution, temperature, and mixing rate were changed separately while other factors were in optimum condition. The results displayed that size and LE are highly influenced by chitosan concentration, getting an optimum of 63 ± 0.57 and 75.19 ± 2.65, respectively, when chitosan concentration was 0.75 mg/ml. Besides, heparin addition time of 3 min leaded to 74.1 ± 0.79 % LE with no sensible effect on size and release profile. In addition, pH 5.5 showed a minimum size of 63 ± 1.87, maximum LE of 73.81 ± 3.13 and the slowest drug release with 63.71 ± 3.84 % during one week. Although LE was not affected by temperature, size and release reduced to 63 ± 0 and 74.21 ± 1.99% when temperature increased from 25°C to 55°C. Also, continuous increase of mixer rate from 500 to 3500 rpm resulted in constant enhancement of LE from 58.3 ± 3.6 to 74.4 ± 2.59 as well as remarkable decrease in size from 148 ± 4.88 to 63 ± 2.64.


Intracranial extension of orbital pseudotumor: a case report.
A patient with intracranial extension of an orbital pseudotumor is reported. This rare consequence of an unusual inflammatory process has been reported on only two previous occasions. Our patient initially presented with unilateral loss of vision and a mass in the sphenoid sinus. Transsphenoidal biopsy revealed inflammatory tissue with a predominance of plasma cells. Over 2 years later, computed tomographic scanning demonstrated involvement of the ipsilateral frontal lobe, and craniotomy revealed invasion of both the dura mater and the cortex by this inflammatory process. Immunohistochemical staining for B and T cells was done to rule out lymphoma, and extensive cultures and staining were performed to identify any infectious process. Because this progressive lesion did not respond to steroid treatment, radiation therapy to the affected area was carried out. Orbital pseudotumor should be considered when an inflammatory process is identified in the meninges and cortex of the anterior fossa.


Spontaneous preoperative pituitary adenoma resolution following apoplexy: a case presentation and literature review.
We aim to more fully understand the incidence and natural history of spontaneously resolving non-functioning pituitary adenomas (NFPAs). We report a case of spontaneous complete resolution of a NFPA revealed by preoperative magnetic resonance imaging. In addition, we searched all major databases and neurosurgery journals to perform a comprehensive literature review of all previously reported cases of spontaneously resolving NFPAs. We discuss how these cases may contribute to our understanding of the natural course for non-functional pituitary adenomas. To date, only twelve cases of spontaneously resolving nonfunctional pituitary adenomas have previously been reported. The presented case is the first reported spontaneously resolved nonfunctioning pituitary adenoma to recur. In all cases, apoplexy resulted in resolution of mass effect, obviating the need for surgical decompression. In all NFPA cases, the preoperative MRI should always be studied closely before surgery is initiated. Additionally, because we have demonstrated that the adenoma may regrow after spontaneous regression following apoplexy, these patients should be followed with regular serial MRIs to monitor for recurrence.


High catalytic activity of silicalite in gas-phase ketonisation of propionic acid.
Amorphous silica and crystalline silicalite (MFI structure) are demonstrated to be active and environmentally benign catalysts for propionic acid ketonisation at 450-500 °C to form 3-pentanone. The silicalite is particularly efficient, and its ketonisation selectivity is increased by base modification probably through generation of silanol nests.


Pharmacokinetic evaluation of ICI 35 868 in man. Single induction doses with different rates of injection.
Blood concentrations of ICI 35 868 have been measured in patients following a single bolus dose of 2 mg kg-1. Three different rates of injection of the anaesthetic agent (3-5s, 20s and 40 or 50s) were examined. Pharmacokinetic indices, derived from blood concentrations of ICI 35 868, were independent of the speed of injection. The blood profiles could be described by a two-compartment open model with a mean alpha-phase half-life of 2.5 min and a mean beta-phase half-life of 54.5 min. The mean total body clearance was 3454 ml min-1. Similar data were obtained from a 4-mg kg-1 dose. The mean recovery time (4.4 min) and concentration of ICI 35 868 at awakening (1.05 micrograms ml-1) were also independent of the rate of injection. Using the derived pharmacokinetic model, predictions of drug concentrations have been made for repeated bolus doses, or infusions, of ICI 35 868.


Thyrotropin-releasing hormone (TRH), a signal peptide of the central nervous system.
Thyrotropin-Releasing Hormone (TRH; pyroGlu-His-Pro-NH2), originally isolated as a hypothalamic neuropeptide hormone, most likely acts also as a neuromodulator and/or neurotransmitter in the central nervous system (CNS). This interpretation is supported by the identification of a peptidase localized on the surface of neuronal cells which has been termed TRH-degrading ectoenzyme (TRH-DE) since it selectively inactivates TRH. Vice versa it also holds true that TRH is selectively inactivated only by TRH-DE and thus, this enzyme might be considered to be the terminator of TRH signals. In situ-hybridization histochemistry was used to study the TRHergic communication system by analyzing the gene expression of TRH-DE in relation to TRH and to the TRH receptors (TRH-R1 and TRH-R2). TRH mRNA is highly expressed in "thyrotropic" hypothalamic regions and in some selected brain areas. For TRH-R1 and TRH-R2, an almost exclusive mRNA distribution pattern was noticed in many brain regions. Interestingly, a widespread distribution of TRH-DE predominantly in neo- and allocortical regions was observed essentially overlapping the distribution patterns of TRH-R1 and TRH-R2. These data support the hypothesis that TRH-DE is important in the TRH-mediated modulation of sensory, locomotor and cognitive functions of the CNS and could be considered to be a marker to map TRHergic pathways.


The BioLuminescent-OptoGenetic in vivo response to coelenterazine is proportional, sensitive, and specific in neocortex.
BioLuminescent (BL) light production can modulate neural activity and behavior through co-expressed OptoGenetic (OG) elements, an approach termed "BL-OG." Yet, the relationship between BL-OG effects and bioluminescent photon emission has not been characterized in vivo. Further, the degree to which BL-OG effects strictly depend on optogenetic mechanisms driven by bioluminescent photons is unknown. Crucial to every neuromodulation method is whether the activator shows a dynamic concentration range driving robust, selective, and nontoxic effects. We systematically tested the effects of four key components of the BL-OG mechanism (luciferin, oxidized luciferin, luciferin vehicle, and bioluminescence), and compared these against effects induced by the Luminopsin-3 (LMO3) BL-OG molecule, a fusion of slow burn Gaussia luciferase (sbGLuc) and Volvox ChannelRhodopsin-1 (VChR1). We performed combined bioluminescence imaging and electrophysiological recordings while injecting specific doses of Coelenterazine (substrate for sbGluc), Coelenteramide (CTM, the oxidized product of CTZ), or CTZ vehicle. CTZ robustly drove activity in mice expressing LMO3, with photon production proportional to firing rate. In contrast, low and moderate doses of CTZ, CTM, or vehicle did not modulate activity in mice that did not express LMO3. We also failed to find bioluminescence effects on neural activity in mice expressing an optogenetically nonsensitive LMO3 variant. We observed weak responses to the highest dose of CTZ in control mice, but these effects were significantly smaller than those observed in the LMO3 group. These results show that in neocortex in vivo, there is a large CTZ range wherein BL-OG effects are specific to its active chemogenetic mechanism.


Comparison of complications of peripherally inserted central catheters with ultrasound guidance or conventional methods in cancer patients.
To compare the complications of peripherally inserted central catheters (PICC) by a modified Seldinger technique under ultrasound guidance or the conventional (peel-away cannula) technique. From February to December of 2010, cancer patients who received PICC at the Department of Chemotherapy in Jiangsu Cancer Hospital were recruited into this study, and designated UPICC if their PICC lines were inserted under ultrasound guidance, otherwise CPICC if were performed by peel-away cannula technique. The rates of successful placement, hemorrhage around the insertion area, phlebitis, comfort of the insertion arm, infection and thrombus related to catheterization were analyzed and compared on days 1, 5 and 6 after PICC and thereafter. A total of 180 cancer patients were recruited, 90 in each group. The rates of successful catheter placement between two groups differed with statistical significance (P<0.05), favoring UPICC. More phlebitis and finger swelling were detected in the CPICC group (P<0.05). From day 6 to the date the catheter was removed and thereafter, more venous thrombosis and a higher rate of discomfort of insertion arms were also observed in the CPICC group. Compared with CPICC, UPICC could improve the rate of successful insertion, reduce catheter related complications and increase comfort of the involved arm, thus deserving to be further investigated in randomized clinical studies.


Universal newborn hearing screening--the Colorado story.
The Colorado State Public Health Department inaugurated a state-wide program of universal newborn hearing screening in 1992. A preliminary report covers the screening of 14,494 infants. 95% passed the screening tests, 5% failed. Of the failures, 6% were found with confirmed hearing losses. The average cost per test was $25.00. Research from the University of Colorado confirms that children receiving intervention by 3 months perform significantly higher at 40 months than those identified later.


[Electrophysiologic effects of intravenous carocainide].
The electrophysiological properties of carocainide a new Class I antiarrhythmic agent (Delalande Research Centre) were studied after intravenous injection of 3.5 mg/kg in 5 minutes in 16 patients aged 24 to 66 years. Five minutes after the injection there was a significant increase (p less than 0.01) in the HV (+/- 12.8 +/- 10.5 msec), AH (+ 21.8 +/- 14 msec) and PR intervals (+ 43.8 +/- 24.2 msec) and in the duration of QRS (+ 20.6 +/- 9.9 msec). The anterograde and retrograde Wenckebach points were decreased (-42 +/- 43 bpm and - 52 +/- 36 bpm respectively, p less than 0.05). All these effects reverted progressively 20 minutes after injection and disappeared by the 40th minute, which corresponds to the pharmaco-kinetic profile of the patient. There were no changes in blood pressure, sinus node function or refractory periods except for the retrograde refractory periods which were prolonged (+ 87 +/- 41 msec). Atrial fibrillation was induced in 2 patients and atrial flutter in 2 others by the extrastimulus technique. These arrhythmias could not be reproduced in these 4 patients during the 40 minutes after injection of carocainide. Five other patients with reciprocating nodal tachycardia induced by atrial extrastimuli had their arrhythmia interrupted by the carocainide injection. We conclude that carocainide acts mainly on atrio-ventricular and intra-ventricular conduction. The results obtained in patients with tachycardias suggest that the product is effective in atrial arrhythmias and paroxysmal junctional tachycardia.


Surface segregation of Au-Pd alloys in UHV and reactive environments: quantification by a catalytic atom probe.
The surface composition of an Au-62at%Pd alloy has been studied by means of a catalytic atom probe (CAP) before and after exposures to nitric oxide (NO) at temperatures ranging from 300 to 573K for 20min. Subsequent CAP analysis at 100K revealed a considerable surface enrichment in Pd (to approximately 80at%) after exposure at 573K. This is correlated with the occurrence of NO dissociation, and the formation of strong Pd-O bonds at the surface. Blank experiments in ultra-high vacuum reflect the surface composition of the bulk material, in excellent agreement with electron microprobe analysis. At 573K, no detectable surface segregation occurs in the absence of NO adsorption for the times and temperatures studied. However, classical Metropolis Monte-Carlo simulations performed with a semi-empirical potential on the Au(40)Pd(60) (111), (110) and (100) systems show surface enrichment of gold at equilibrium. This suggests that the temperatures of the clean surface segregation experiments are too low to reach equilibrium within times of the order of hours.


Vibrational spectra, NLO analysis, and HOMO-LUMO studies of 2-chloro-6-fluorobenzoic acid and 3,4-dichlorobenzoic acid by density functional method.
The FTIR and FT-Raman spectra of 2-chloro-6-fluorobenzoic acid and 3,4-dichlorobenzoic acid have been recorded in the region 4000-400 cm(-1) and 3500-50 cm(-1), respectively. Utilizing the observed FTIR and FT-Raman data, a complete vibrational assignment and analysis of fundamental modes of the compounds were carried out. The optimized molecular geometries, vibrational frequencies, thermodynamic properties and atomic charge of the compounds were calculated by using density functional theory (B3LYP) method with 6-311+G and 6-311++G basis sets. The difference between the observed and scaled wave number values of most of fundamentals is very small. Unambiguous vibration assignment of all the fundamentals is made up the total energy distribution (TED). The calculated HOMO and LUMO energies show that charge transfer occurs within the molecules. Besides, molecular electro static potential (MESP), Mulliken's charge analysis, first order hyper polarizability and several thermodynamic properties were performed by the DFT method.


Clinical trials with canine distemper vaccines in exotic carnivores.
Two types of killed canine distemper virus (CDV) vaccine and a modified-live CDV vaccine were clinically evaluated in four species of exotic carnivores. In 16 trials in which 13 red pandas (Ailurus fulgens) were given the killed vaccine, only 1 animal had a virus-neutralization titer that exceeded 1:100. A red panda given modified-live CDV vaccine deemed safe for gray foxes and ferrets died of bacterial pneumonia 16 days later. There was no pathologic evidence of canine distemper in that panda. The same modified-live vaccine proved to be immunogenic and safe in 12 bush dogs (Speothos venaticus), 5 maned wolves (Chrysocyon brachyurus), and 3 fennec foxes (Fennecus zerda) in which virus-neutralization titers often exceeded 1:512 and persisted for several months after vaccination.


Bioactivities of a Ti surface ablated with a femtosecond laser through SBF.
Micro-patterns with deposited calcium/phosphorus (Ca/P) elements on a pure titanium (Ti) surface were synthesized in 2.5 x simulated body fluid (SBF) by femtosecond laser ablation, and their bioactivities were evaluated by co-culture with osteoblasts. Scanning electron microscope observation showed that a three-order roughness micro-pattern, which was composed of grooves, islands, holes and sub-micro-particles, was obtained, and the size of holes and islands was increased from 0.5 µm and 2 µm to 5 µm and 6 µm, respectively, gradually with the increase of laser fluence from 3.3 J cm(-2) to 12.5 J cm(-2). Irradiation of femtosecond lasers promoted the deposition of Ca/P on the surface of a Ti plate. The osteoblasts grew faster and extended more slender filopodia on the femtosecond laser-ablated surface than on a sand blast followed by an acid surface, which demonstrated that the micro-patterns with deposited Ca/P on the surface were favorable for osteoblasts' growth.


[Epidemiology of Haemophilus influenzae strains identified in 2001 in France, and assessment of their susceptibility to beta-lactams].
The aim of this study was to describe the epidemiology of H. influenzae strains collected in 2001 at the National Reference Center and to evaluate their susceptibility to beta-lactams. The demographic characteristics were recorded for each strain, then were determined their capsular serotyping (slide agglutination with specific antisera), as well as their beta-lactamase production (chromogenic cephalosporin test, Nitrocefin), and their MICs (agar dilution method on Haemophilus Test Medium) for amoxicillin (AMX), co-amoxiclav (AMC), cefpodoxime (CPD), cefaclor (CEC), cefuroxime (CXM), and cefotaxime (CTX). 41.3% of the 752 strains were identified in bronchial secretions, 20.6% in conjunctivitis, 11.3% in otitis media, and 11% in blood cultures. 96.3% of the strains were not capsulated and 3.7% were of type b, d, e or f. 33.8% of the strains were beta-lactamase producers (TEM type), 45.8% of these were identified in otitis pus and 27.7% in bronchial secretions. One hundred and forty-two strains (18.9%) presented reduced susceptibility to beta-lactams (modification of target) associated or not with bla+. MICs 50/90 against bla+ strains were: AMX 1/32, AMC 0.12/1, CTX 0.007/0.03, CPD 0.03/0.12, CEC 1/64, CXM 0.25/1. Against low BLNAR and bla+ strains, MICs 50/90 were: AMX 2/32, AMC 0.25/2, CTX 0.015/0.06, CPD 0.06/0.25, CEC 4/64, CXM 0.25/4. And against low BLNAR strains MICs 50/90 were: AMX 0.25/8, AMC 0.25/8, CTX 0.015/0.12, CPD 0.06/0.50, CEC 4/32, CXM 0.25/4. Both bla+ and modifications of PBP are widespread among strains isolated in France. CTX, and CPD remain the most active compounds whatever the resistance mechanisms.


Efficacy and safety of aliskiren and amlodipine combination therapy in patients with hypertension: a randomized, double-blind, multifactorial study.
Most patients with hypertension need more than one drug to achieve blood pressure (BP) control. This randomized, double-blind, multifactorial study evaluated whether combinations of aliskiren and amlodipine provided superior BP reductions to component monotherapies in patients with hypertension (mean sitting diastolic BP (msDBP) 95-<110 mm Hg). Overall, 1688 patients were randomized to once-daily monotherapy with aliskiren 150 or 300 mg or amlodipine 5 or 10 mg, combination therapy with one of four corresponding aliskiren/amlodipine doses, or placebo for 8 weeks. At week 8 end point, aliskiren/amlodipine combinations provided significant msDBP reductions from baseline of 14.0-16.5 mm Hg, compared with reductions of 8.0 and 10.2 mm Hg for aliskiren 150 and 300 mg, respectively (P<0.001), and 11.0 and 13.8 mm Hg for amlodipine 5 and 10 mg, respectively (P<0.05). Aliskiren/amlodipine combinations provided reductions in mean sitting systolic BP 20.6-23.9 mm Hg, compared with decreases of 10.7 and 15.4 mm Hg for aliskiren 150 and 300 mg, respectively (P<0.001), and 15.8 and 21.0 mm Hg for amlodipine 5 (P< or =0.001) and 10 mg (P=NS), respectively. Aliskiren/amlodipine combination therapy provides greater BP lowering than either agent alone, hence offering an effective treatment option for patients with hypertension.


Determination of orthotropic bone elastic constants using FEA and modal analysis.
Finite element models have been widely employed in an effort to quantify the stress and strain distribution around implanted prostheses and to explore the influence of these distributions on their long-term stability. In order to provide meaningful predictions, such models must contain an appropriate reflection of mechanical properties. Detailed geometrical and density information is now readily available from CT scanning. However, despite the use of phantoms, a method of determining mechanical properties (or elastic constants) from bone density has yet to be made available in a usable form. In this study, a cadaveric bone was CT scanned and its natural frequencies were measured using modal analysis. Using the geometry obtained from the CT scan data, a finite element mesh was created with the distribution of density established by matching the mass of the FE bone model with the mass of the cadaveric bone. The maximum values of the orthotropic elastic constants were then established by matching the predictions from FE modal analyses to the experimental natural frequencies, giving a maximum error of 7.8% over 4 modes of vibration. Finally, the elastic constants of the bone derived from the analyses were compared with those measured using ultrasound techniques. This produced a difference of <1% for both the maximum density and axial Young's Modulus. This study has thereby produced an orthotropic finite element model of a human femur. More importantly, however, is the implication that it is possible to create a valid FE model by simply comparing the FE results with the measured resonant frequency of the CT scanned bone.


Adjustments of the enzymatic complement for polyol biosynthesis and accumulation in diapausing cold-acclimated adults of Pyrrhocoris apterus.
The capacity to accumulate winter polyols (mainly ribitol and sorbitol) during cold-acclimation in Pyrrhocoris apterus is restricted only to the adults that have previously entered diapause. The enzymatic complement involved in polyol biosynthesis was found to differ in a complex manner between diapause and non-diapause adults. Nearly 100% of glycogen phosphorylase (GPase) was present in its active form in non-diapause adults irrespective of their acclimation status. In contrast, less than 40% of GPase was present in its active form in diapause adults prior to cold-acclimation and the inactive form was rapidly activated upon transition from 5 to 0 degrees C, concomitantly with the start of rapid polyol accumulation. The flow of carbon released by activation of glycogen degradation might be routed to the pentose cycle because the activity of glucose-6-P dehydrogenase (G(6)P-DH) was significantly higher and it increased with cold-acclimation in diapause adults while it was relatively low and it decreased with cold-acclimation in non-diapause adults. Reducing equivalents in the form of NADPH, which were generated in the pentose cycle, might require re-oxidation. Such re-oxidation might be achieved during reduction of sugars to polyols. The activity of NADP(H)-dependent aldose reductase (AR) was about 20-fold higher in diapause than in non-diapause adults. Similarly, the activity of NAD(H)-dependent polyol dehydrogenase (PDH) was higher in diapause adults. In addition, we found a very high activity of an unusual enzyme, NADP(H)-dependent ketose reductase (KR), exclusively in diapause adults. KR might be involved in reduction of fructose to sorbitol. Although its affinity for fructose as a substrate was low (K(M)=0.64M), its activity was about 10-fold higher than that of PDH with fructose. Moreover, the activity of KR significantly increased with cold-acclimation while that of PDH remained unchanged. Different electrophoretic mobilities in PAGE gel suggested that KR and PDH are two different enzymes with specific requirement for NADP(H) or NAD(H), respectively, as co-factors.


A role for Na/K adenosine triphosphatase in the pathogenesis of cyst formation in experimental polycystic kidney disease.
Multiple cyst formation with fluid retention is a characteristic structural abnormality in polycystic kidney disease (PKD). Na/K adenosine triphosphatase (ATPase) is a major transporting membrane protein that is ubiquitous in the epithelial cell, which has been thought to be involved in cystogenesis. We have investigated the molecular and histologic basis of Na/K ATPase activity in experimental PKD in vivo. Rats were treated with diphenylthiazole (100 mg/100 gm body weight), and cyst formation was examined histologically. Na/K ATPase activity was measured enzymatically by using a fluorometric method, and reverse transcription-competitive polymerase chain reaction (RT-PCR) analysis was used to quantitate mRNA levels in the isolated single nephron segment. Kidneys were immunostained with subunit-specific antibodies to determine the localization of Na/K ATPase in the epithelial cell. The enzyme activity increased in the cortical collecting duct from 25.9 +/- 3.5 mmol/Lpmol/mm/min to 72.9 +/- 6.8 pmol/mm/min and in the outer medullary collecting duct from 13.0 +/- 3.9 mmol/Lpmol/mm/min to 58.5 +/- 9.8 pmol/mm/min (n = 6, p < 0.01); however, all other segments showed no significant changes. No significant alternation in alpha 1- and beta 1-subunits of Na/K ATPase mRNA levels was observed by competitive PCR assay in either segment. The enzyme was stained at the basolateral membrane even in the cystic tubules. Na/K ATPase activity was up-regulated in the cyst-formed kidney, but this was not accompanied with transcriptional up-regulation. Increased Na/K ATPase activity at normal locations may play a role in abnormal net fluid transport in the development and progression of experimental PKD.


Metal-chelate dye-controlled organization of Cd32S14(SPh)40(4-) nanoclusters into three-dimensional molecular and covalent open architecture.
Chalcogenide II-VI nanoclusters are usually prepared as isolated clusters and have defied numerous efforts to join them into covalent open-framework architecture with conventional templating methods such as protonated amines or inorganic cations commonly used to direct the formation of porous frameworks. Herein, we report the first templated synthesis of II-VI covalent superlattices from large II-VI tetrahedral clusters (i.e., [Cd32S14(SPh)38]2-). Our method takes advantage of low charge density of metal-chelate dyes that is a unique match with three-dimensional II-VI semiconductor frameworks in charge density, surface hydrophilicity-hydrophobicity, and spatial organization. In addition, metal-chelate dyes also serve to tune the optical properties of resulting dye semiconductor composite materials.


The effects of two different swimming training periodization on physiological parameters at various exercise intensities.
This study analysed the effects of two different periodization strategies on physiological parameters at various exercise intensities in competitive swimmers. Seventeen athletes of both sexes were divided to two groups, the traditional periodization (TPG, n = 7) and the reverse periodization group (RPG, n = 10). Each group followed a 10-week training period based on the two different periodization strategies. Before and after training, swimming velocity (SV), energy expenditure (EE), energy cost (EC) and percentage of aerobic (%Aer) and anaerobic (%An) energy contribution to the swimming intensities corresponding to the aerobic threshold (AerT), the anaerobic threshold (AnT) and the velocity at maximal oxygen uptake (vVO2max) were measured. Both groups increased the %An at the AerT and AnT intensity (P ≤ .05). In contrast, at the AnT intensity, EE and EC were only increased in TPG. Complementary, %Aer, %An, EE and EC at vVO2max did not alter in both groups (P > .05); no changes were observed in SV in TPG and RPG at all three intensities. These results indicate that both periodization schemes confer almost analogous adaptations in specific physiological parameters in competitive swimmers. However, given the large difference in the total training volume between the two groups, it is suggested that the implementation of the reverse periodization model is an effective and time-efficient strategy to improve performance mainly for swimming events where the AnT is an important performance indicator.


The measurement of psychological well-being in the person with aphasia.
This paper will introduce the construct of psychological well-being and discuss its relevance to speech and language therapy. Measures of psychological well-being are used routinely in psychological contexts, both as diagnostic and research indicators, and also as outcome measures. There is not a tradition of measuring psychological well-being in the speech and language therapy context, yet the clinical significance of well-being to therapeutic outcome is recognised. This paper will evaluate the existing measures available and discuss the development and validation of the Visual Analogue Self Esteem Scale for use with aphasic speakers (Brumfitt and Sheeran, 1998). Problems inherent in evaluating self-knowledge in communicatively disordered speakers will be discussed.


A charge neutral, size tuneable polymersome capable of high biological encapsulation efficiency and cell permeation.
The field of therapeutics is evolving to include a greater proportion of higher molecular weight, hydrophilic biological compounds. To cater for this new era in healthcare the concomitant development of appropriate drug delivery systems is essential to aid cellular permeation. In this manuscript we present the synthesis, characterisation and biological evaluation of a charge neutral polymersome (Ps) based drug delivery system (DDS) using an amphiphilic pegylated random copolymer. A detailed dynamic light scattering study revealed that the hydrodynamic diameter of the Ps can be tailored to a specific size simply by varying the quantities and ratios used during the preparation step. The zeta potential of this new drug delivery system was determined to be -0.095 ± 0.037 mV, the encapsulation efficiency of Fitc-CM-Dextran (4 KDa) was 70%, the uptake of Fitc-CM-Dextran by Hela cells was increased 4-fold when encapsulated within the polymersomal system. The facile preparation, high loading capacity and size tuneable nature of this Ps renders it a promising alternative to the ever growing array of currently available Ps.


A novel halogen bond and a better-known hydrogen bond cooperation of neonicotinoid and insect nicotinic acetylcholine receptor recognition.
Neonicotinoid insecticides target the insect nicotinic acetylcholine receptor (nAChR) and are highly effective against the piercing-sucking pests. To explore the molecular interaction mechanism between the neonicotinoids and the insect nAChR, some key neonicotinoid compounds were docked into Aplysia californica acetylcholine binding protein (Ac-AChBP), which serves as a suitable structural surrogate of the insect nAChR. The binding mode study showed that the hydrogen bond force between the electronegative pharmacophore of the neonicotinoids and Cys190NH of the target binding pocket is crucial to the high efficiency of the neonicotinoids. Increasing the coplanarity between the guanidine or amidine and the electronegative pharmacophore of the neonicotinoids could increase the Π-Π stacking effect with Tyr188 of the Ac-AChBP and thus enhance the insecticidal potency. The introduction of an azide group to the chloropyridine ring of the neonicotinoids would reduce its binding ability due to the disappearance of a novel halogen bonding interaction. A series of novel neonicotinoid molecules were designed based on the halogen bonding interaction and two compounds with 6-bromopyridine-3-yl and 6-(trifluoromethyl)-3-pyridinyl were found to be with potential insecticidal activities.


[Factors associated with the degree of disability among patients of the Spanish Multiple Sclerosis Association of the Community of Madrid].
Multiple sclerosis (MS) causes a degree of disability in young adults which hampers everyday activities. The aetiology and predisposing factors are unknown. To find the degree of disability (DD) and index of progression (IP) together with the possible associated prognostic factors in MS patients of the Spanish Multiple Sclerosis Association (AEDEM). Transverse design based on the population (AEDEM) by means of a representative sample (N = 158), taken randomly from those not suffering an exacerbation of MS. A telephone survey was carried out using the 'Minimum Dossier of Invalidity of MS' (eliminating variables concerning neurological dysfunction). The relationship between DD and IP, with different variables, was compared using parametric and non-parametric tests. Variables associated with the evolution of DD were measured in terms of the Odds Ratio. The response rate was 150 (94.9%), 10 (6.7%) were rejected, giving a total of 140 patients. 55% of the patients considered themselves to be independent to some degree, in that they had no difficulty with everyday activities. Difficulty with walking was the 'most disabling problem' of 47.1%. Progression of the disorder (IP) depended on the frequency of exacerbations (r = 0.63). The variables associated with a raised DD are: suffer more than 5 exacerbations (OR: 3.73), have had the illness for more than 15 years (OR = 3.29) and a current age of over 35 years old (OR = 2.86). The reduction in number and frequency of exacerbations or their prevention may reduce progression of the disorder and disability in daily life.


[The mechanisms of a decreased tolerance for graduated physical loading in young patients suffering from diabetes mellitus].
A study of graded exercise tolerance (GET), indices of central hemodynamics and energy metabolism in 136 patients with insulin-dependent diabetes mellitus and 35 controls aged 16 to 40 has shown reduced GET in 86% of the patients. It was combined with a decrease in the CVS functional potentialities and disorder of energy formation. The lowest level of GET was noted in patients with a severe type of diabetes mellitus in marked decompensation, with disease of 10 yrs. of duration at advanced stages of diabetic microangiopathies. The use of inosine and AMP is accompanied by a rise of GET and the activity of energy producing systems.


Alcoholic hepatitis.
Alcoholic hepatitis is a serious consequence of alcohol misuse and the usual precursor of cirrhosis. Risk factors, histology, pathogenesis, clinical features, prognosis and treatment are discussed in this review.


Secretion of ERP57 is important for extracellular matrix accumulation and progression of renal fibrosis, and is an early sign of disease onset.
Renal fibrosis is characterized by excessive accumulation of extracellular matrix (ECM), which compromises organ function by replacing normal organ tissue. The molecular mechanisms leading to renal fibrosis are not fully understood. Here we demonstrated that TGFβ1, AGT or PDGF stimulation of renal cells resulted in endoplasmic reticulum (ER) stress followed by activation of the protective unfolded protein response pathway and a high secretory level of protein disulfide isomerase ERP57 (also known as PDIA3). The TGFβ1-induced impairment of ER function could be reversed by treatment with BMP7, suggesting a specific involvement in renal fibrosis. A clear correlation between the degree of fibrosis, ER stress and the level of ERP57 could be seen in fibrosis animal models and in biopsies of renal fibrosis patients. Protein interaction studies revealed that secreted ERP57 exhibits a strong interaction with ECM proteins. Knockdown of ERP57 or antibody-targeted inhibition of the secreted form significantly impaired the secretion and accumulation of ECM. Moreover, ERP57 was excreted in the early stages of chronic kidney disease, and its level in urine correlated with the degree of renal fibrosis, suggesting that the secretion of ERP57 represents one of the first signs of renal fibrosis onset and progression.


Demographic and urban form correlates of healthful and unhealthful food availability in Montréal, Canada.
This study sought to extend previous analyses of food insecurity in Montreal by examining the relationship between neighbourhood sociodemographic and urban form variables and sources of food both unhealthful (fast-food outlets, FFO) and healthful (stores selling fruits and vegetables, FVS). Densities of FFO and FVS were computed for 862 Census tract areas (CTA) (defined as census tract with a 1-km buffer around its limits) for the Montréal Census Metropolitan Area (CMA). Predictor variables included CTA socio-demographic characteristics reflecting income, household structure, language, and education, and urban form measures, specifically, densities of local roads, main roads, expressways and highways. Food source densities were regressed on CTA characteristics using stepwise regression. Socio-demographic and urban form measures explained 60% and 73% of the variance in densities of FFO and FVS, respectively. FFO were more prevalent in CTA with higher proportions of full-time students and households speaking neither French nor English; lower proportions of married individuals, children and older adults; and more high-traffic roads. FVS were more prevalent in CTA with higher proportions of single residents, university-educated residents and households speaking neither French nor English; lower proportion of French-speakers; and more local roads. Median household income was not related to the density of FFO or FVS. The availability of healthful and unhealthful food varies across the Montréal CMA. Areas with lower education and more French-speaking households have a lesser availability of FVS. The association of FFO with high-traffic roadways and areas with high school attendance suggests a point for intervention via commercial zoning changes.


Parallel solid-phase synthesis of disubstituted (5-biphenyltetrazolyl) hydantoins and thiohydantoins targeting the growth hormone secretagogue receptor.
An efficient solid-phase protocol for the synthesis of substituted (5-biphenyltetrazolyl)-hydantoins and -thiohydantoins has been developed. Suzuki cross-coupling between resin-bound 2-(tetrazol-5-yl)-phenylborinane and 4-bromobenzaldehyde gave the corresponding tetrazolylbiphenyl aldehyde. Subsequent reductive amination using amino acid esters gave the pivotal resin bound amino acid esters which were transformed to hydantoins or thiohydantoins via two routes: (i) treatment with isocyanates or isothiocyanates or (ii) successive treatment with triphosgene and primary amines. Using molecular modeling, we were able to jump from L-692,429, a well known non-peptidyl growth hormone secretagogue (GHS), to biphenyltetrazolyl hydantoins, obtaining compounds with IC(50) values below 600 nM after two iterative cycles only.


[Colonic metabolism of fiber].
Over the last few years, the colon has come to be considered more and more as a central digestive organ. This is where bacterial fermentation takes place to eliminate the substrates, mostly carbohydrates, that have avoided digestion by human enzymes within the small intestine. Of these, fibre plays a prominent role. As a result of this colonic fermentation, short-chain fatty acids are created and these have an important function at the level of the colon (reduction in pH, trophic effect, energy production, etc.) and at the systemic level (lipid metabolism, glycaemic metabolism, etc.) No less important are the effects of this colonic metabolism of fibre on proliferation of bacteria, thus giving fibre probiotic effects.


Cobalt(II) complexes of terpyridine bases as photochemotherapeutic agents showing cellular uptake and photocytotoxicity in visible light.
Cobalt(II) complexes of terpyridine bases [Co(L)₂](ClO₄)₂ (1-3), where L is 4'-phenyl-2,2':6',2''-terpyridine (ph-tpy in 1), 4'-(9-anthracenyl)-2,2':6',2''-terpyridine (an-tpy in 2) and 4'-(1- pyrenyl)-2,2':6',2''-terpyridine (py-tpy in 3), are prepared and their photo-induced DNA and protein cleavage activity and photocytotoxic property in HeLa cells studied. The 1 : 2 electrolytic and three-electron paramagnetic complexes show a visible band near 550 nm in DMF-Tris-HCl buffer. The complexes 1-3 show emission spectral bands at 355, 421 and 454 nm, respectively, when excited at 287, 368 and 335 nm. The quantum yield values for 1-3 in DMF-H₂O (2 : 1 v/v) are 0.025, 0.060 and 0.28, respectively. The complexes are redox active in DMF-0.1 M TBAP. The Co(III)-Co(II) and Co(II)-Co(I) couples appear as quasi-reversible cyclic voltammetric responses near 0.2 and -0.7 V vs. SCE, respectively. Complexes 2 and 3 are avid binders to calf thymus DNA giving K(b) value of ∼10⁶ M⁻¹. The complexes show chemical nuclease activity. Complexes 2 and 3 exhibit oxidative cleavage of pUC19 DNA in UV-A and visible light. The DNA photocleavage reaction of 3 at 365 nm shows formation of singlet oxygen and hydroxyl radical species, while only hydroxyl radical formation is evidenced in visible light. Complexes 2 and 3 show non-specific photo-induced bovine serum albumin protein cleavage activity at 365 nm. The an-tpy and py-tpy complexes exhibit significant photocytotoxicity in HeLa cervical cancer cells on exposure to visible light giving IC₅₀ values of 24.2 and 7.6 μM, respectively. Live cell imaging study shows accumulation of the complexes in the cytosol of HeLa cancer cells.


Coulomb drag between one-dimensional conductors
We have analyzed Coulomb drag between currents of interacting electrons in two parallel one-dimensional conductors of finite length L attached to external reservoirs. For strong coupling, the relative fluctuations of electron density in the conductors acquire energy gap M. At energies larger than gamma = constxv(-)exp(-LM/v(-))/L+gamma(+), where gamma(+) is the impurity scattering rate, and, for L>v(-)/M, where v(-) is the fluctuation velocity, the gap leads to an "ideal" drag with almost equal currents in the conductors. At low energies the drag is suppressed by coherent instanton tunneling, and the zero-temperature transconductance vanishes, indicating the Fermi-liquid behavior.


Phylogeny of Na+/Ca2+ exchanger (NCX) genes from genomic data identifies new gene duplications and a new family member in fish species.
The Na+/Ca2+ exchanger (NCX) is a member of the cation/Ca2+ antiporter (CaCA) family and plays a key role in maintaining cellular Ca2+ homeostasis in a variety of cell types. NCX is present in a diverse group of organisms and exhibits high overall identity across species. To date, three separate genes, i.e., NCX1, NCX2, and NCX3, have been identified in mammals. However, phylogenetic analysis of the exchanger has been hindered by the lack of nonmammalian NCX sequences. In this study, we expand and diversify the list of NCX sequences by identifying NCX homologs from whole-genome sequences accessible through the Ensembl Genome Browser. We identified and annotated 13 new NCX sequences, including 4 from zebrafish, 4 from Japanese pufferfish, 2 from chicken, and 1 each from honeybee, mosquito, and chimpanzee. Examination of NCX gene structure, together with construction of phylogenetic trees, provided novel insights into the molecular evolution of NCX and allowed us to more accurately annotate NCX gene names. For the first time, we report the existence of NCX2 and NCX3 in organisms other than mammals, yielding the hypothesis that two serial NCX gene duplications occurred around the time vertebrates and invertebrates diverged. In addition, we have found a putative new NCX protein, named NCX4, that is related to NCX1 but has been observed only in fish species genomes. These findings present a stronger foundation for our understanding of the molecular evolution of the NCX gene family and provide a framework for further NCX phylogenetic and molecular studies.


Baclofen as an adjuvant analgesic for cancer pain.
Baclofen is a g-aminobutyric acid receptor agonist commonly used for managing many types of neuropathic pain. The effect of baclofen on cancer pain has not previously been studied. This retrospective study evaluated the efficacy of baclofen in patients with cancer pain. We reviewed the medical records of all patients given baclofen orally as an analgesic for cancer at 5 institutions. Twenty-five patients received 10 to 40 mg of baclofen for cancer pain relief. Twenty patients have undergone neuropathic pain such as paroxysmal or lancing, sharp, or like an electric shock. Baclofen was effective in 21 of 25 patients and significantly reduced Numeric Rating Scale (pain score, 0-10; P < .0001). Nine patients reported mild adverse events: none of these 9 patients had to discontinue baclofen due to adverse events. Our findings suggest that baclofen may be a useful adjuvant analgesic in the treatment of cancer pain.


Edge states of hydrogen terminated monolayer materials: silicene, germanene and stanene ribbons.
We investigate the energy dispersion of the edge states in zigzag silicene, germanene and stanene nanoribbons with and without hydrogen termination based on a multi-orbital tight-binding model. Since the low buckled structures are crucial for these materials, both the π and σ orbitals have a strong influence on the edge states, different from the case for graphene nanoribbons. The obtained dispersion of helical edge states is nonlinear, similar to that obtained by first-principles calculations. On the other hand, the dispersion derived from the single-orbital tight-binding model is always linear. Therefore, we find that the non-linearity comes from the multi-orbital effects, and accurate results cannot be obtained by the single-orbital model but can be obtained by the multi-orbital tight-binding model. We show that the multi-orbital model is essential for correctly understanding the dispersion of the edge states in tetragen nanoribbons with a low buckled geometry.


A 3D MRI sequence for computer assisted surgery of the lumbar spine.
The aim of this research was to develop a magnetic resonance (MR) sequence capable of producing images suitable for use with computer assisted surgery (CAS) of the lumbar spine. These images needed good tissue contrast between bone and soft tissue to allow for image segmentation and generation of a 3D-surface model of the bone for surface registration. A 3D double echo fast gradient echo sequence was designed. Images were filtered for noise and non-uniformity and combined into a single data set. Registration experiments were carried out to directly compare segmentation of MR and computed tomography (CT) images using a physical model of a spine. These experiments showed the MR data produced adequate surface registration in 90% of the experiments compared to 100% with CT data. The MR images acquired using the sequence and processing described in this article are suitable to be used with CAS of the spine.


Photoperiodic sensitivity of prepubertal female Fisher 344 rats.
The laboratory rat is thought to be a poor model for study of the photoperiodic control of reproduction; however, this has only been investigated in a few rat strains. The purpose of the present investigation was to determine if the neuroendocrine-reproductive system of the Fisher 344 (F344) rat, an inbred strain, is sensitive to light deprivation. All treatments were performed on 28-day-old female F344 rats and the animals maintained for 8 weeks in a 14:10 light:dark cycle. Blinding resulted in a 65% (P less than 0.01) reduction in uterine weight and a 25% (P less than 0.01) decrease in ovarian weight. Accompanying these reductions in blinded animals were significant inhibitions of anterior pituitary weight, serum prolactin levels, and pituitary prolactin synthesis as measured in vitro. Pinealectomy of the blinded animals prevented all of these effects. Additionally, when olfactory bulbectomy, a procedure known to sensitize rats to the effects of photoperiod, was combined with blinding, the results did not differ significantly from that found with blinding alone. From these data we conclude that 1) the neuroendocrine-reproductive system of the prepubertal F344 female rat is highly sensitive to light deprivation; 2) light deprivation produces its antigonadotrophic effect through the pineal gland; and 3) olfactory bulbectomy does not potentiate the effects of blinding in the F344 rat.