Soil-transmitted helminth infections and taeniasis on Samosir Island, Indonesia.
Soil-transmitted helminth (STH) infections are important causes of morbidity in poorer areas of developing countries, with high endemicity in Southeast Asia. Humans are most often exposed to the infective forms of STHs in areas with sub-standard sanitation. The number of STH infections globally was estimated at 1.5 billion in 2018. In Indonesia, the prevalence of STH infections ranges from 2.5% to 62.0%. STH and taeniasis infections were evaluated on Samosir Island, North Sumatra, Indonesia. Field surveys were conducted in January 2003, February 2005, and February 2006 in Simanindo Subdistrict, with a subsequent survey conducted in the subdistricts of Simanindo and Ronggurnihuta in September 2015. A total of 371 individuals were screened between 2003 and 2006 and 368 were screened in 2015 (314 from Simanindo and 54 from Ronggurnihuta). Fecal samples were collected and examined microscopically by the Kato-Katz technique. The prevalence of STH infections in Simanindo for the years 2003, 2005, 2006, and 2015 was 41.4%, 52.2%, 55.7%, and 46.8%, respectively. The 2015 prevalence of STH infections in Ronggurnihuta was 66.7%. Taenia asiatica taeniasis prevalence was 3.4% and 2.2% for the years 2003 and 2005, respectively, with no cases detected in 2006 or 2015. The prevalence of STH infections in Simanindo and Ronggurnihuta was similar to other STH prevalence values reported for Indonesia. Country-level values have not changed substantially from those reported in the 1980s and 1990s, where prevalence ranged from 40% to 70%. Improvement of personal hygiene and environmental sanitation for control of STH infections on Samosir Island will require collaboration among multiple sectors.


Formation of a Ring-Shaped Reduced "Metal Oxide" with the Simple Composition [(MoO3 )176 (H2 O)80 H32 ].
The largest inorganic molecular system so far, [(MoO3 )176 (H2 O)80 H32 ] (1; the picture on the right shows the polyhedral representation), which has been characterized by X-ray structure analysis, possesses a cavity of diameter 2.3 nm and remarkably shows the stoichiometry of a (reduced) protonated and hydrated "molecular molybdenum trioxide". It is formed by reduction of an aqueous solution of lithium molybdate with tin(II) chloride at very high H+ concentrations.


Persons with schizophrenia migrate towards urban areas due to the development of their disorder or its prodromata.
Many studies have identified urban-rural differences in the occurrence of schizophrenia. Though unknown, the underlying causes responsible for these differences have been hypothesized to include urban-rural differences in toxic exposures, diet, infections, stress, or an artifact due to selective migration. Freeman hypothesized that persons with schizophrenia migrate towards larger cities due to development of their disorder or its prodromata. Based on this, the reason for the high frequency of schizophrenia in urban areas is not that those affected have lived in environmentally unfavorable areas, but that people with schizophrenia selectively migrate towards urban areas due to disease onset. No population-based studies accessed the extent and potential impact of this artifact of selective migration. Utilizing a population-based sample of the Danish population, it was investigated if persons with schizophrenia more often migrated towards larger cities due to disease onset. The impact of selective migration on the urban-rural differences was quantified comparing a prospective and a retrospective study. Compared to healthy controls, persons with schizophrenia spectrum disorder migrate to a higher degree of urbanization due to disease onset (OR=1.18 (1.14-1.23)). However, the bias in urban-rural effect sizes due to this artifact of selective migration was limited. Persons with schizophrenia drift towards urban areas as a consequence of the disorder or its prodromata, but this drift has only limited impact on the urban-rural differences. Therefore, prospective and retrospective studies are both informative on the unknown underlying factor or factors responsible for the urban-rural differences in schizophrenia risk.


Anterior cruciate ligament reconstruction: evaluation with MR imaging.
Fifty magnetic resonance (MR) imaging examinations were performed in 37 patients after arthroscopic anterior cruciate ligament (ACL) reconstruction with patellar bone-tendon-tibial bone autografts. T1-weighted sagittal and axial images were obtained. In 34 patients with clinically stable ACL autografts, 43 of 47 MR examinations demonstrated a well-defined, intact ACL autograft. All three patients with ACL laxity failed to demonstrate a well-defined autograft, for an overall correlation between MR imaging and clinical examination results of 92%. Of the 12 patients who underwent second-look arthroscopy, 100% correlation was present between MR imaging and arthroscopic results. As in the nonreconstructed knee, buckling of the posterior cruciate ligament was suggestive of ACL laxity. MR imaging also documented optimum placement of bone tunnels in the femur and tibia. MR imaging has proved to be an excellent noninvasive imaging modality for evaluating ACL reconstruction, while also providing ancillary information about the postoperative knee.


Risk factors for tibial damage associated with the modified Maquet technique in 174 stifles.
To identify risk factors for tibial damage associated with the modified Maquet technique (MMT) in dogs with cranial cruciate ligament (CCL) disease. Retrospective study. One hundred and seventy-four stifles from 147 client-owned dogs. Medical records of dogs diagnosed with CCL disease and treated with the current version of MMT were reviewed. Dogs were included if immediate postoperative radiographs were available. Cortical hinge fracture or fissure, tibial tuberosity fracture, and diaphyseal fractures of the tibia were recorded. Age, body weight (BW), thickness of the tibial cortical hinge, and angle of opening of the osteotomy were tested as potential risk factors for tibial damage by univariate logistic regression analysis. Tibial damage included intraoperative tibial fissures in 37% of MMTs, intraoperative fractures of the cortical hinge in 3.4% of MMTs, postoperative tibial fractures in 14% of MMTs. Risk factors for intraoperative fissure included BW (P = .0153) and thickness of cortical hinge (P = .0006). The angle of opening of the osteotomy was identified as a risk factor for intraoperative cortical hinge fracture (P = .0034), angles below 11° being preventive. No risk factor was identified for postoperative fracture. Based on these results, preventive measures against tibial damage associated with MMT should include: a thickness of cortical hinge based on the equation related to the BW; a length of osteotomy adjusted to the amount of TTA with an osteotomy angle below 10°; and slow advancement of the tibial tuberosity.


Off-label use of ketamine for treatment-resistant depression in clinical practice: European perspective.
SummaryKetamine therapy for treatment-resistant depression in European national health systems may only be considered after attempting all evidence-based antidepressant strategies outlined in clinical guidelines. This paper seeks to explain the ethical, regulatory and procedural framework for the off-label use of ketamine for treatment-resistant depression within a public healthcare system.Declaration of interestNone.


Symptom dimensions of the SCL-90-R: a test of the tripartite model of anxiety and depression.
To determine the extent to which the SCL-90-R assesses general distress or specific dimensions of psychopathology, two principal components analyses were conducted based on 900 outpatients diagnosed with mixed psychiatric disorders. The first component explained 30.5% of the total variance and was interpreted as reflecting overall symptom distress. Partialling the first component out of the correlations among the symptoms in a second principal components analysis, we found four specific residual components reflecting somatic anxiety, depression, irritability, and attention problems. The results were discussed as partially supporting Clark and Watson's (1991) tripartite model of anxiety and depression.


Effect of aspirin in coronary artery bypass grafting.
To evaluate the effect of aspirin (ASA) therapy on postoperative blood loss, transfusion requirements, reoperation for bleeding, duration of stay in the intensive care unit and in the hospital in a selected population undergoing a first coronary artery bypass grafting (CABG) surgery. Prospective observational study in consecutive patients during a 3-month period. A teaching cardiothoracic center. Two hundred forty consecutive patients undergoing elective coronary artery bypass grafting surgery for the first time. Two hundred forty consecutive patients admitted for a first CABG the day before surgery were visited. patients with an abnormal routine coagulation screen or taking drugs that might have affected their coagulation mechanisms were prospectively excluded (n = 96). The date of the last dose of ASA was recorded in the 144 remaining patients, and data were acquired prospectively. Total mediastinal blood drainage, blood products usage, reopening, and duration of intensive care unit and hospital stay were recorded. Patients were grouped by days free of ASA. There were no significant differences detected between groups. In patients undergoing a first CABG and with no known factors affecting their coagulation, ASA therapy did not appear to increase blood loss, reopening for bleeding, or blood products usage requirements during the hospital stay. ASA therapy did not influence the duration of stay in intensive care or in the hospital.


Staphylococcus aureus Resistance Patterns in Wisconsin: 2018 Surveillance of Wisconsin Organisms for Trends in Antimicrobial Resistance and Epidemiology (SWOTARE) Program Report.
Surveillance of antimicrobial resistance patterns on a local level can reveal paradigms not obvious on a regional or national scale. Data collection from this perspective may potentially impact local prescribing patterns and empiric treatment guidelines. The objective of this study was to establish a baseline Staphylococcus aureus antibiogram for the state of Wisconsin and to elucidate potential geographic and demographic factors associated with antimicrobial resistance. Multi-center laboratory surveillance, with testing at a single site utilizing standardized media and susceptibility testing protocols. 309 isolates of clinically-significant S. aureus were collected from hospital microbiology laboratories across Wisconsin in 2018, with distribution across seven geographic regions. Each isolate was tested using reference broth microdilution methods against a panel of 15 antimicrobial agents. Percentage susceptibility data, as well as median and 90th percentile minimum inhibitory concentration (MIC) values, were computed for each antimicrobial agent as a function of geographic region or demographic category. Increased resistance to penicillin (≥ 86.0% of isolates), erythromycin (≥ 56.8%), cefoxitin (≥ 45.5%), levofloxacin (≥ 25.0%), and clindamycin (≥ 20.5%) was observed in the Southcentral, Lake Winnebago, and Southeast regions of Wisconsin. In addition, isolates phenotypically classified as methicillin-resistant S. aureus (MRSA) were found to have increased rates of resistance to clindamycin, erythromycin, and levofloxacin as compared to S. aureus isolates susceptible to cefoxitin. S. aureus isolates demonstrated nearly 100% in vitro susceptibility to ceftaroline, dalbavancin, and telavancin. Statewide S. aureus isolates exhibited a vancomycin MIC90 of 1 μg/mL. S. aureus isolates from patients aged 20-39 years were more likely to demonstrate cefoxitin resistance when compared to other age groups (P ≤ 0.03), while isolates from patients ≥ 80 years were more likely to exhibit resistance to levofloxacin and clindamycin (P ≤ 0.046). Several antimicrobial agents continue to demonstrate in vitro efficacy against clinical isolates of S. aureus (including MRSA) throughout Wisconsin, including three agents with recently-published susceptibility testing guidelines. However, continued surveillance efforts may be necessary in the Lake Winnebago, Southeast, and Southcentral regions to further assess higher rates of resistance to a number of antimicrobial agents.


Long-term phosphodiesterase 5 inhibitor administration reduces inflammatory markers and heat-shock proteins in cavernous tissue of Zucker diabetic fatty rat (ZDF/fa/fa).
Oxidative stress and nitrosative stress present in type 2 diabetes mellitus (T2DM) and metabolic syndrome (MS) induce inflammatory response in diverse tissues including cavernous tissue (CT). Heat-shock proteins (HSPs) have an important role in modulating and repairing tissue injury, although their participation in CT in T2DM is unclear. Beyond the specific action of phosphodiesterase type 5 inhibitors (PDE5i) on erectile function, it has been proposed that chronic administration of these agents improves endothelial function and ameliorates fibrotic changes. The aim of this study was to determine in CT of Zucker Diabetic Fatty (ZDF) rat, an experimental model of T2DM and MS: (1) the degree of oxidative stress and nitrosative stress; (2) the magnitude of inflammatory markers such as tumor necrosis factor-α (TNFα) and interleukin 6 (IL6); (3) immunoexpression of HSP70 and HSP27; (4) how a long-term PDE5i administration may modify these variables. For 6 months, (1) untreated ZDF; (2) ZDF+Sildenafil (Sil) and (3) control Lean Zucker Rat (LZR) received no treatment, were studied. Penises were processed for functional 'in vitro' studies, oxidative and nitrosative stress evaluation and immunohistochemistry in CT using TNFα; IL6; nitrotyrosine, HSP70 and HSP27 antibodies. ZDF+Sil presented better relaxation in corporal strips versus untreated ZDF. Furthermore, ZDF+Sil presented less lipoperoxidation in CT versus untreated ZDF. The activity of antioxidant enzymes CuZn superoxide dismutase (CuZnSOD) and glutathione peroxidase (GPx) was also reduced in untreated ZDF in CT along with a decrease in glutathione versus untreated ZDF. Nitrotyrosine expression was increased in untreated-ZDF rats versus ZDF+Sil and LZR. TNFα and IL6 were decreased in CT in ZDF+Sil versus untreated ZDF. Additionally, the expression of HSP70 and HSP27 was reduced in CT in ZDF+Sil versus untreated ZDF. In conclusion, this study provides substantial evidence supporting a protective role of a long-term therapy with Sil on CT in a recognized animal model of T2DM and MS.


Pseudo-orthogonalization of memory patterns for associative memory.
A new method for improving the storage capacity of associative memory models on a neural network is proposed. The storage capacity of the network increases in proportion to the network size in the case of random patterns, but, in general, the capacity suffers from correlation among memory patterns. Numerous solutions to this problem have been proposed so far, but their high computational cost limits their scalability. In this paper, we propose a novel and simple solution that is locally computable without any iteration. Our method involves XNOR masking of the original memory patterns with random patterns, and the masked patterns and masks are concatenated. The resulting decorrelated patterns allow higher storage capacity at the cost of the pattern length. Furthermore, the increase in the pattern length can be reduced through blockwise masking, which results in a small amount of capacity loss. Movie replay and image recognition are presented as examples to demonstrate the scalability of the proposed method.


Gouty tophus presenting as a soft-tissue mass diagnosed by fine-needle aspiration: a case report.
We present a case in which a primary diagnosis of gout was made by fine-needle aspiration. The patient had a right distal ulnar mass, and the initial clinical and radiological diagnoses were that of giant cell tumor of tendon sheath. While tophi are the hallmark of gout, they rarely undergo aspiration because of the known clinical history. This case demonstrates that a tophus may mimic a soft-tissue neoplasm. Whenever an aspiration yields amorphous or granular material, the cytopathologist should be aware of and consider gouty tophus as a diagnostic possibility and perform compensated polarized microscopy on the specimen smears.


Social Rank and Rejection Sensitivity as Mediators of the Relationship between Insecure Attachment and Disordered Eating.
The current study assessed a new interpersonal model for eating disorders (EDs), in which interpersonal rejection sensitivity (RS), appearance-based RS and social rank were hypothesised to mediate the relationship between insecure attachment and disordered eating. The sample comprised a clinical ED group (N = 122) and a control group (N = 622). Participants were asked to complete a number of self-report measures related to the variables of interest. Invariance testing indicated that the model was structurally non-invariant (different across groups). For the ED group, appearance-based RS and social rank were significant mediators of the relationship between insecure attachment and disordered eating. For the controls, the relationship between insecure attachment and disordered eating was mediated through multiple pathways involving interpersonal RS, appearance-based RS and social rank. These findings may inform existing therapies such as interpersonal psychotherapy for EDs, by emphasising the role of sensitivity to rejection in the development and maintenance of disordered eating. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.


Distribution of radiolabeled alloantibodies in mice bearing 3-methylcholanthrene-induced sarcoma.
The distribution of purified 125I-labeled alloantibodies, prepared from the serum of DBA/2J mice obtained after immunization with C3H/HeJ spleen cells, was studied in immunosuppressed DBA/2J mice bearing either allogeneic C3H/HeJ 3-methylcholanthrene sarcomas growing s.c. or syngeneic SaD2 3-methylcholanthrene sarcomas. Once purified radiolabeled antibody was isolated from 125I-labeled immune gamma-globulin by a single adsorption onto C3H/HeJ RBC and elution from stroma prepared from these cells, by using 0.1 M glycine buffer (pH 3.0). Twice-purified alloantibody was then produced by Bio-Gel P-200 or Sephadex G-200 gel filtration chromatography or DEAE A-50 ion-exchange chromatography. In vitro, such purified antibodies bound specifically to C3H/HeJ RBC. In vivo, they localized to a significant extent following i.p. injection, preferentially in C3H/HeJ 3-methylcholanthrene sarcomas (4.4 to 8.9% of the injected dose per g of tumor equal to 1% of mouse weight), with mean tumor/blood ratios of 4.0 to 7.8, at 24 or 48 hr after injection. The percentage of injected dose localized in tumor and the tumor/blood ratio did not show significant differences with respect to time or method of antibody purification. Normal tissue/blood ratios in C3H/HeJ or SaD2 sarcoma-bearing mice were less than 0.9. The tumor/blood ratios in SaD2 sarcomas were approximately 0.6. Injection of 131I-labeled normal DBA/2J gamma-globulin resulted in normal tissue/blood and tumor/blood ratios of less than 0.9 in C3H/HeJ tumor-bearing mice.


The reduction of pain on injection of propofol: the effect of addition of lignocaine.
The effects of addition of 1 ml of lignocaine (10 mg) or isotonic saline to 19 ml of the emulsified preparation of propofol (Diprivan) were studied in a randomised, double-blind trial in 80 patients. The incidence and severity of pain on injection of propofol were significantly reduced by the addition of lignocaine (P less than 0.01).


Cyclic AMP induces ultrastructural differentiation of normal adult human adrenocortical cells cultured in vitro.
Electron microscopic studies have revealed that cyclic AMP, like ACTH, induces structural differentiation of adult human adreno-cortical cells cultured in vitro. These findings support the hypothesis that cyclic AMP can function as an intracellular mediator of the action of ACTH on the human adrenal gland.


Psychological stress in patients with anal fistula.
Psychological stress is known to affect the immunologic system and the inflammatory response. The aim of this study was to assess the presence of psychological stress, anxiety, and depression in patients with anal fistula. Consecutive patients with anal fistula, hemorrhoids, and normal volunteers were studied prospectively. Stressful life events were recorded and subjects were asked to complete the state-trait anxiety inventory (STAI), a depression scale, and three different reactive graphic tests (RGT). Seventy-eight fistula patients, 73 patients with grade III-IV hemorrhoids, and 37 normal volunteers were enrolled. Of the fistula patients, 65 (83 %) reported one or more stressful events in the year prior to diagnosis, compared to 16 (22 %) of the hemorrhoid patients (P = 0.001). There were no significant differences in the percentage of subjects with abnormal trait anxiety (i.e., proneness for anxiety) and depression scores between fistula patients, hemorrhoid patients, and controls. Fistula patients had significantly higher (i.e., better) scores compared to hemorrhoid patients in two of three RGT and significantly lower (i.e., worse) scores in all three RGT compared to healthy volunteers. Of 37 patients followed up for a median of 28 months (range 19-41 months) after surgery, 8 (21.6 %) had persistent or recurrent sepsis. There was no significant difference in depression, STAI, and RGT scores between patients with sepsis and patients whose fistula healed. Our results suggest that an altered emotional state plays an important role in the pathogenesis of anal fistula and underline the importance of psychological screening in patients with anorectal disorders.


Further evidence of an early critical period in the development of the cat's dorsal lateral geniculate nucleus.
The concept of an early postnatal critical period of development for the lateral geniculate nucleus was assessed by determining in adult cats whether previously established properties of geniculate neurons could be altered by varying the cat's visual experience. The analysis was limited to lamina A1 and the binocular segment of lamina A, and the properties studied were the percentage of physiologically recorded Y-cells and cell soma size. Eleven experimental cats in four groups were studied, and three cats reared normally plus three cats reared with continuous monocular lid suture served as controls. Two cats raised first with monocular suture followed by a prolonged period in adulthood with both eyes open had cell size distributions and Y-cell proportions that were indistinguishable from cats raised with continuous monocular suture. Four cats raised first with one eye sutured underwent a reverse suture procedure in adulthood (i.e., the originally sutured eye opened and the other closed) and were maintained in this fashion for a prolonged period. These cats also had geniculate cell size distributions and Y-cell proportions that were indistinguishable from cats raised with continuous monocular suture. Two cats were raised first with binocular suture followed by a prolonged period in adulthood with one eye opened. Their geniculate cell size distributions and Y-cell proportions showed no effect on the adult monocular deprivation and were indistinguishable from previously published data concerning cats raised with continuous binocular suture. Finally, three normally raised cats underwent a prolonged period of monocular suture in adulthood. Their geniculate cell size distributions and Y-cell proportions showed no effects on the adult monocular deprivation. From these data, we conclude that an early critical period of development occurs for geniculate cell sizes and Y-cell proportions. Adult visual environments, whether normal or abnormal, had no detectable effect on geniculate neurons for these previously developed properties, whether normal or abnormal.


Langerhans cells and T-lymphocytes in the normal human ectocervix defined by monoclonal antibodies and electron microscopy.
Slices of normal human uterine ectocervix, obtained from hysterectomized patients, were processed for immunohistological labelling in cryostat frozen sections and the adjacent slices fixed for electron microscopy. This combined procedure was chosen to localize two surface antigens (T6 and HLA-DR) in Langerhans cells and to identify this type of cell by the ultrastructural marker, the Birbeck granule. A third monoclonal antibody (T8) was used to label a population of migrating lymphocytes which appear near the Langerhans cells as well as in the lamina propria. The electron micrographs reveal that both Langerhans cells and T lymphocytes occupy the intercellular channels of the cervical epithelium. It is postulated that in the female genital tract Langerhans cells may function as an antigen presenting cell for T lymphocytes in normal physiological conditions.


Therapeutic effects of topical doxycycline in a benzalkonium chloride-induced mouse dry eye model.
We investigated the therapeutic effects and underlying mechanisms of topical doxycycline in a benzalkonium chloride (BAC)-induced mouse dry eye model. Eye drops containing 0.025%, 0.1% doxycycline or solvent were administered to a BAC-induced dry eye model four times daily. The clinical evaluations, including tear break-up time (BUT), fluorescein staining, inflammatory index, and tear volume, were performed on days 0, 1, 4, 7, and 10. Global specimens were collected on day 10 and processed for immunofluorescent staining, TUNEL, and periodic acid-Schiff assay. The levels of inflammatory mediators in the corneas were determined by real-time PCR. The total and phosphorylated nuclear factor-κB (NF-κB) were detected by Western blot. Both 0.025% and 0.1% doxycycline treatments resulted in increased BUT, lower fluorescein staining scores, and inflammatory index on days 4, 7, and 10, while no significant change in tear volume was observed. The 0.1% doxycycline-treated group showed more improvements in decreasing fluorescein staining scores, increasing Ki-67-positive cells, and decreasing TUNEL- and keratin-10-positive cells than other groups. The mucin-filled goblet cells in conjunctivas were increased, and the expression of CD11b and levels of matrix metalloproteinase-9, IL-1β, IL-6, TNF-α, macrophage inflammatory protein-2, and cytokine-induced neutrophil chemoattractant in corneas were decreased in both doxycycline-treated groups. In addition, doxycycline significantly reduced the phosphorylation of NF-κB activated in the BAC-treated corneas. Topical doxycycline showed clinical improvements and alleviated ocular surface inflammation on BAC-induced mouse dry eye, suggesting a potential as an anti-inflammatory agent in the clinical treatment of dry eye.


Clinical features of symptomatic uncomplicated diverticular disease: a multicenter Italian survey.
Clinical features of symptomatic uncomplicated diverticular disease are poorly investigated. Abdominal symptoms may be similar to those of irritable bowel syndrome. This survey aimed to assess clinical features associated with symptomatic uncomplicated diverticular disease. This multicenter survey included consecutive outpatients with symptomatic uncomplicated diverticular disease to whom a detailed clinical questionnaire regarding demographic, lifestyle, and clinical features was administered. Diagnosis was based on the presence of diverticula and abdominal pain/discomfort. Irritable bowel syndrome and functional dyspepsia were assessed according to Rome III criteria. A total of 598 patients (50 % female, age 69 years), 71 % with newly diagnosed symptomatic uncomplicated diverticular disease and 29 % with history of colonic diverticula, were recruited. Diverticula were localized in the left colon in 78 % of the patients. Recurrent short-lived abdominal pain (<24 h) was present in 70 % (relieved by evacuation in 73 %), prolonged abdominal pain (>24 h) in 27 %, and recurrent abdominal bloating in 61 % of the patients. Normal, loose, or hard stools were reported by 58, 29, and 13 % of patients, respectively. Irritable bowel syndrome (IBS)-like and functional dyspepsia-like symptoms were recorded in 59 and 7 % of patients, respectively. IBS-like symptoms (odds ratio, 4.3) were associated in patients with prolonged abdominal pain. Symptomatic uncomplicated diverticular disease is associated with a gender ratio of 1:1 and an unspecific clinical picture mainly characterized by normal stools, short-lived abdominal pain, abdominal bloating, IBS-like symptoms, while functional dyspepsia-like symptoms are not commonly present. These findings suggest that symptomatic uncomplicated diverticular disease often shows similar findings rather than overlaps IBS.


[Study of spectral interferences of REEs with the matrix of dy for a high resolution ICP-AES].
The spectral interferences of the matrix of Dy on other REEs have been studied for a high resolution ICP-AES with a grating of 3600 grooves/mm. 66 analytical lines of 14 REEs have been selected as the prominent lines in the spectral interference studies. Three kinds of databases for Dy lines have been established for the spectra search and recognition. Thus, these databases can provide information of Dy lines accurately and conveniently.


Myelin oligodendrocyte glycoprotein-positive optic neuritis masquerading as pseudotumor cerebri at presentation.
Optic neuritis (ON) is a common clinical manifestation in myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease. Other clinical manifestations include acute demyelinating encephalomyelitis, transverse myelitis and neuromyelitis optica spectrum disorders. Uncommon presentations of MOG-positive disease have recently been reported. ON in MOG-positive disease commonly involves the anterior portion of both optic nerves, leading to bilateral disc swelling. During the early stages of ON, in the setting of bilateral disc swelling and pain, patients may initially be suspected as pseudotumor cerebri (PTC). In this study, we report five cases presenting early in the course of MOG-IgG-related ON, which were misdiagnosed as PTC in the emergency department. MOG-IgG-positive ON requires timely treatment to prevent RNFL and vision loss secondary to the high relapse rate associated with these antibodies. Our aim is to increase the awareness of the unique findings of MOG-IgG-positive ON, which may initially mimic PTC, thereby delaying treatment.


Clinicopathologic correlates predict the outcome in children with steroid-resistant idiopathic nephrotic syndrome treated with pulse methylprednisolone therapy.
Although pulse methylprednisolone therapy (PMT) has been used successfully in the management of children with steroid-resistant nephrotic syndrome (SRNS), the relationship between initial presenting findings and renal histological characteristics to the subsequent clinical response to PMT is unknown. A retrospective analysis was conducted in a study cohort of 42 children (30 boys, 12 girls; mean age, 7.4 +/- 4.7 years) with SRNS administered PMT between June 1976 and July 1994 at Stanford University (Stanford, CA). Four diagnostic categories were created: group I, minimal change disease with or without mesangial hypercellularity (n = 10); group II, mesangial proliferation (n = 7); group III, focal segmental glomerulosclerosis (FSGS) with or without mesangial hypercellularity (n = 10); and group IV, FSGS plus mesangial proliferation (n = 15). Primary variables analyzed were remission in response to PMT with or without alkylating agent therapy and end-stage renal disease (ESRD). Remission rates were best in group I (90%) and worst in group IV (46%). With the exception of hematuria, presenting clinical features did not correlate with outcome. Segmental sclerosis, glomerular adhesion to Bowman's capsule, epithelial sloughing, corona (segmental scar surrounded by visceral epithelial cells), subepithelial deposits, inflammatory cells, and percentage of interstitium, immunoglobulin M (IgM), IgG, and C3 deposition univariately correlated with ESRD in univariate analysis. In a multivariate logistic regression model, only segmental sclerosis (P = 0.008) correlated with ESRD. Histological analysis is important because it identifies features, including segmental sclerosis, that portend a poor prognosis in children with SRNS.


The effects of rest interval and resistance training on quadriceps femoris muscle. Part II: EMG and perceived exertion.
The purpose of this study was to examine the effects of rest interval on quadriceps femoris muscle activation and perceived exertion, during short-term resistance training. Vastus medialis (VM) and vastus lateralis (VL) muscle electromyograms (EMG) were assessed in 15 males during a sustained 80% maximal voluntary contraction (MVC). During the pre-training evaluation, the absolute value of the 80% MVC (N.m) and contraction duration (s) was performed at 2, 4, and 6 weeks during the training period. Perceived exertion was measured via the Borg category-ratio scale every 5 s during the 80% MVC. Subjects were randomly assigned to 3 groups: group 1 received a 40 s rest interval in between exercise sets, group 2 received a rest period of 160 s, and the control group did not participate in training. Groups 1 and 2 performed isokinetic knee extensions at 180 deg.s(-1) 2 days per week for 6 weeks. The results demonstrated a significant decrease in VM EMG within the initial portion of the 80% MVC across the training period in the short rest interval group. The long rest interval and control groups showed no significant changes in VM EMG during 1st part of the contraction across the training period, whereas the control group exhibited a significant reduction in VL EMG across weeks 4 to 6. VL EMG increased during the 80% MVC in the control group across the training period. VM EMG increased during the sustained contractions in the long rest interval and control groups across the training period. The perceived exertion response was lower in the 1st part of the 80% MVC in the short and long rest interval groups, but not in the control group, across the training period. The results also showed a significant decrease in perceived exertion at the end of the sustained contraction in the short rest interval group, but not in the long rest interval group or the control group. The findings from this study suggest that the application of relatively short rest intervals in between sets of resistance exercise induced a greater neuromuscular response of the VM muscle during short-term training.


Analysis of mutations and identification of several polymorphisms in the putative promoter region of the P34CDC2-related CDC2L1 gene located at 1P36 in melanoma cell lines and melanoma families.
Chromosome 1 abnormalities are the most commonly detected aberrations in many cancers including malignant melanoma. Partial deletions and an allelic loss of the chromosome 1p36 region observed in melanoma indicate the presence of putative tumor suppressor gene(s) in this region. A candidate gene, CDC2L1, which encodes PITSLRE proteins related to p34(cdc2), is mapped to 1p36. To determine whether CDC2L1 mutation is involved in melanoma development, we examined 20 melanoma cell lines and 11 members of melanoma-prone families linked to chromosome 1p36. Mutation analysis throughout the entire coding region of the CDC2L1 gene revealed only 1 mutation (C-->T at nucleotide location 97 of exon 7, Ser-->Leu) in the melanoma cell line UACC 903 out of 20 melanoma cell lines and 6 melanoma cases. However, 4 polymorphic nucleotide changes, C-48T, G-53C, T-103C and T-210C, in the putative promoter region of CDC2L1 were identified. The 4 variants were located within or beside the conserved binding sites of transcription factors TCF11, MZF1 and TAAC box, indicating their potential effects on the regulation of CDC2L1 expression. No aberrant methylation of the CDC2L1 CpG island in the promoter region was observed by sodium bisulfite genomic sequencing. These results indicate that mutations are rare in the CDC2L1 gene in these melanoma cell lines and melanoma families and that the aberrant cytosine methylation of the CDC2L1 CpG island is not the mechanism of CDC2L1 repression in melanoma. The contribution of 4 promoter polymorphisms to the transcriptional regulation of the gene and its association with melanoma warrants further investigation.


Diabetic patients on renal replacement therapy: analysis of Catalan Registry data. Renal Registry Committee.
In recent years, a progressive increase in the need of renal replacement therapy has been noted for patients with diabetes mellitus. The present report is based on an analysis of the data of the 'Registre de Malats Renals de Catalunya' (RMRC). It was the aim to identify (i) the incidence and prevalence of diabetic patients on renal replacement therapy, (ii) associated diseases, (iii) the relative risk of different modes of treatment, and (iv) the rate of death compared to non-diabetic patients on renal replacement therapy and in the general population. Of the 936 diabetic patients starting renal replacement therapy during the period 1984-1994, 24.8% were classified as DN and IDDM, 65.7% as DN and NIDDM, and in 9.5%, diabetes accompanied renal failure from standard primary renal disease. The incidence of diabetic patients has increased from 3 per million population (pmp) in 1984 to 26.6 pmp in 1994. At any given age the risk of requiring renal replacement therapy with diabetes was 1.5-fold higher in males than in females. Of diabetic patients who were < 45 years of age, 55% received a renal transplant and > 50% lived with a simultaneous kidney/pancreas graft. For diabetic patients above this age, haemodialysis was the most prevalent form of treatment. Morbidity in diabetic patients was higher than in the overall RMRC population. Cardiac and vascular disease were the most prominent complications. Mortality of diabetic patients on renal replacement therapy was twice that of the overall population of RMRC and 16-fold higher than in the general population of Catalunya. The risk of death increased with age and was higher in patients with reduced functional autonomy. Transplanted patients had a smaller risk than patients on haemodialysis or CAPD. Survival has increased for patients starting treatment after 1990 compared to the period 1984-1989. In conclusion, diabetes mellitus is one of the main causes leading to renal replacement therapy in Catalunya. Diabetic patients are more multimorbid than the rest of the population of the Registre de Malats Renals de Catalunya. These observations call for the institution of primary or secondary prevention.


Spatial-scale effects on relative importance of physical habitat predictors of stream health.
A common theme in recent landscape studies is the comparison of riparian and watershed land use as predictors of stream health. The objective of this study was to compare the performance of reach-scale habitat and remotely assessed watershed-scale habitat as predictors of stream health over varying spatial extents. Stream health was measured with scores on a fish index of biotic integrity (IBI) using data from 95 stream reaches in the Eastern Corn Belt Plain (ECBP) ecoregion of Indiana. Watersheds hierarchically nested within the ecoregion were used to regroup sampling locations to represent varying spatial extents. Reach habitat was represented by metrics of a qualitative habitat evaluation index, whereas watershed variables were represented by riparian forest, geomorphology, and hydrologic indices. The importance of reach- versus watershed-scale variables was measured by multiple regression model adjusted-R2 and best subset comparisons in the general linear statistical framework. Watershed models had adjusted-R2 ranging from 0.25 to 0.93 and reach models had adjusted-R2 ranging from 0.09 to 0.86. Better-fitting models were associated with smaller spatial extents. Watershed models explained about 15% more variation in IBI scores than reach models on average. Variety of surficial geology contributed to decline in model predictive power. Results should be interpreted bearing in mind that reach habitat was qualitatively measured and only fish assemblages were used to measure stream health. Riparian forest and length-slope (LS) factor were the most important watershed-scale variables and mostly positively correlated with IBI scores, whereas substrate and riffle-pool quality were the important reach-scale variables in the ECBP.


Effect of method of administration of psyllium on glycemic response and carbohydrate digestibility.
To determine whether there was any advantage to taking a soluble fiber supplement separate from food, as opposed to incorporated into a food, we used psyllium as a model, either taken in water just before a flaked bran cereal test meal, sprinkled on top of the cereal, or actually incorporated into the flake. In normal subjects, psyllium reduced the glycemic response when sprinkled onto or incorporated into the cereal, but not when taken before the cereal. Varying the amount of psyllium incorporated into the cereal from 0 to 20% resulted in a linear dose-dependent reduction of the glycemic index (GI) (GI = 101 -2.2 x % psyllium; r = 0.950; p less than 0.002). In subjects with diabetes, the blood-glucose-lowering effect of the psyllium flake cereal was similar to that in normal subjects. Mixing psyllium with the cereal or incorporating it into the cereal reduced the rate of digestion of bran flakes in vitro but was not associated with increased breath hydrogen levels in vivo as an index of rapid colonic fermentation. The bran flakes with psyllium incorporated was rated as no less palatable than the bran flakes cereal alone, and significantly more palatable (p less than 0.05) than taking psyllium in water before the cereal or sprinkling psyllium onto the cereal. These studies confirm earlier reports that viscous fibers must be intimately mixed with the food to have the effect of reducing blood glucose responses, and that the mechanism of action relates to a reduced rate of digestion rather than carbohydrate malabsorption.(ABSTRACT TRUNCATED AT 250 WORDS)


Successful reoperation for severe left bronchus compression after repair of persistent truncus arteriosus with interrupted aortic arch.
Signs of the left bronchus compression, caused by aneurysmatic dilatation of the aortic root with severe aortic regurgitation, occurred 5 months after repair of the truncus arteriosus with interrupted aortic arch in an 85-day-old infant. At reoperation the dilated ascending aorta was replaced with a 14-mm Dacron tube. The aortic valve was replaced with an 18-mm Carbomedics valve. Compression of the left bronchus and the right pulmonary artery were released. The right pulmonary artery was enlarged with a pericardial patch and the original homograft was replaced with a new one. The patient remains in good clinical condition 2 years later.


Ion mobility mass spectrometry of peptide, protein, and protein complex ions using a radio-frequency confining drift cell.
Ion mobility mass spectrometry experiments enable the characterization of mass, assembly, and shape of biological molecules and assemblies. Here, a new radio-frequency confining drift cell is characterized and used to measure the mobilities of peptide, protein, and protein complex ions. The new drift cell replaced the traveling-wave ion mobility cell in a Waters Synapt G2 HDMS. Methods for operating the drift cell and determining collision cross section values using this experimental set up are presented within the context of the original instrument control software. Collision cross sections for 349 cations and anions are reported, 155 of which are for ions that have not been characterized previously using ion mobility. The values for the remaining ions are similar to those determined using a previous radio-frequency confining drift cell and drift tubes without radial confinement. Using this device under 2 Torr of helium gas and an optimized drift voltage, denatured and native-like ions exhibited average apparent resolving powers of 14.2 and 16.5, respectively. For ions with high mobility, which are also low in mass, the apparent resolving power is limited by contributions from ion gating. In contrast, the arrival-time distributions of low-mobility, native-like ions are not well explained using only contributions from ion gating and diffusion. For those species, the widths of arrival-time distributions are most consistent with the presence of multiple structures in the gas phase.


Human xenograft-nude mouse model of adoptive immunotherapy with human melanoma-specific cytotoxic T-cells.
We investigated the efficacy of human melanoma-specific cytotoxic T-cells (CTLs) in treating experimental human melanoma metastases in a nude mouse model of adoptive immunotherapy. Hepatic metastases were generated by the intrasplenic injection of 1.5 x 10(6) human melanoma cells. Animals were then randomized to receive saline, interleukin-2 only, or CTLs and interleukin-2. CTLs were effective when administered 3 or 7 days after generation of hepatic metastases, with 96 and 88% of animals disease-free, respectively, when examined at one month. Interleukin-2 alone was not effective. In addition, CTLs were effective when as few as 2.5 x 10(6) T-cells were adoptively transferred. Only 33% of the animals were tumor-free when CTLs were administered on day 10, and CTLs were not effective when given at day 14. Human CTLs that were not cytotoxic for the tumor line used in vivo, when tested in a 51Cr assay, were also not effective in the model of immunotherapy. This suggests that the tumor-specific CTLs maintain their specificity in vivo, and eliminates a nonspecific inflammation directed against the human CTLs as a possible cause of the antitumor effect. These studies lay the foundation for clinical trials of CTLs in the adoptive immunotherapy of patients with metastatic melanoma.


Girdlestone arthroplasty for infected total hip arthroplasty.
Results of a previous study of 21 patients who underwent conversion of infected total hip arthroplasties to Girdlestone resection arthroplasties suggested that Girdlestone resection arthroplasty provides a functionally poor salvage technique and is often painful. The present study was undertaken to assess further the salvage value of Girdlestone arthroplasties for the treatment of infected total hips. Fourteen additional cases were reviewed, summarizing the clinical experience of the past three years. These more recent data support the conclusion that resection arthroplasty provides a poor functional result when used as a salvage procedure following removal of infected total hip components. Of the 14 patients reviewed, only one obtained an acceptable functional result. The initial 21 patients studied were re-reviewed to obtain further follow-up data. The functional results obtained were essentially unchanged and are comparable with those from the series of 14 patients reviewed in this study. In some cases of infected total hip arthroplasty, resection arthroplasty is the best method of treatment available, but the results are often far from ideal. Direct or indirect prothesis exchange is an alternative in some cases. Total hip arthroplasty should not be recommended for the young patient who has one or two joint diseases and no limiting systemic factors, with the expectation that when the total hip fails, it can be converted to a resection arthroplasty and the patient improved as compared with the pre-total hip status. It may be wiser to utilize another procedure, e.g., fusion, resection arthroplasty, or osteotomy, primarily, and then revise to a total hip, if necessary, when the patient is older.


Three-dimensional analysis of alveolar wall destruction in the early stage of pulmonary emphysema.
The morphological mechanism of alveolar wall destruction during pulmonary emphysema has not been clarified. The aim of this study was to elucidate this process three-dimensionally. Lung specimens from five patients with pulmonary emphysema were used, and five controls with normal alveolar structure were also examined. Sections 150 μm thick were stained with hematoxylin and eosin, elastica, and silver impregnation, and immunostained with selected antibodies. We examined these sections three-dimensionally using a laser confocal microscope and a light microscope. There were only a few Kohn's pores and no fenestrae in the normal alveoli from the controls. In the lungs of the emphysema patients a small rupture appeared in the extremely thin alveolar wall among the alveolar capillaries. This rupture enlarged to form a circle surrounded by the capillaries, which was called an alveolar fenestra. Two neighboring fenestrae fused by breakdown of the collapsed or cord-like capillary between them to form a large fenestra. The large fenestrae fused repeatedly to become larger, and these were bordered by thick elastic fibers constructing an alveolar framework. Alveolar wall destruction during emphysema could start from small ruptures of the alveolar wall that become fenestrae surrounded by capillaries, which fuse repeatedly to become larger fenestrae rimmed with elastic fibers. The alveolar capillary network could initially prevent enlargement of the fenestrae, and the thick elastic fibers constituting the alveolar framework could secondarily prevent destruction of the alveolar wall structure.


In vitro effect of lymphoblastoid alpha-interferon on subpopulations of effector cells mediating cytotoxicity for autologous hepatocytes in hepatitis B and non-A, non-B.
Controlled clinical trials are currently under way to assess the efficacy of interferon (IFN) in hepatitis B virus (HBV) infection. In the present study, T-enriched and non-T-enriched lymphocytes from six patients with acute and six patients with chronic HBV infection were cocultured with autologous liver cells with and without alpha-IFN (lymphoblastoid) at a concentration of 1000 U/ml of culture medium, in an 18 h cytotoxicity assay. IFN produced a significant enhancement of non-T-cell cytotoxicity in patients with acute and chronic HBV infection, from 34.3 +/- 19.6% to 60.0 +/- 11.2%, P less than 0.03, and from 41.2 +/- 17.2% to 65.5 +/- 9.8%, P less than 0.01, respectively. In contrast, no significant effect was observed on T cell-mediated cytotoxicity in either group of patients. The in vitro effect of alpha-IFN was also evaluated in four patients who developed chronic non-A, non-B hepatitis following blood transfusion, but no significant stimulatory effect was noted on either T- or non-T cell cytotoxicity. Similarly, no significant increase was observed in control subjects. The significant enhancement of non-T cell cytotoxicity, but not of T-cell cytotoxicity, for autologous hepatocytes in HBV infection suggests that alpha-IFN produces a selective stimulatory effect on non-T cells. The absence of a similar effect in patients with chronic non-A, non-B hepatitis and control subjects suggests that HBV infection alters the susceptibility of hepatocytes to IFN-stimulated non-T cell damage.


Use of avian influenza vaccination in Hong Kong.
Outbreaks of H5N1 highly pathogenic avian influenza (HPAI) that occurred in Hong Kong up until February/March 2002 were controlled by stamping out. With endemic presence of the virus in the region and large daily importation of poultry to Hong Kong, the Administration considered that further risk management measures, in addition to improved biosecurity and enhanced surveillance, were necessary to prevent outbreaks. Vaccination using a killed H5N2 vaccine was evaluated over a 12-month period in the district with the last HPAI cases in the early 2002 outbreak. The vaccination trial showed that farmer-administered killed H5N2 vaccine produced suitable flock antibody responses; vaccinated birds were protected against H5N1 HPAI virus challenge and excreted significantly less H5N1 virus; and vaccination was able to control virus excretion in flocks during field outbreaks. Universal vaccination of local chicken farms was introduced in June 2003 and by the end of 2003 all chickens entering the live poultry markets in Hong Kong were vaccinated by killed H5N2 vaccine. In addition to vaccination, an enhanced biosecurity programme on farms and in live poultry markets and a comprehensive surveillance programme in poultry, wild birds, recreation park birds and pet birds were in place. Vaccination use and performance is closely monitored. This programme was successful in protecting local farms and live poultry markets from H5N1 outbreaks during the regional H5N1 outbreaks in 2004.


Effects of electrolyte concentration on the rotational dynamics of resorufin.
We report on the rotational diffusion dynamics of the anionic chromophore resorufin in water and N-octyl-2-pyrrolidone (NOP) solutions as a function of solution electrolyte concentration. Our data show that resorufin exhibits a single exponential anisotropy decay in aqueous solutions containing up to 0.1 M lithium perchlorate (LiClO(4)). In contrast to the observed behavior of resorufin in pure NOP, where biexponential decay occurs, we also observe a single exponential anisotropy decay for resorufin in NOP with the addition of up to 0.1 M tetrabutylammonium bromide (TBAB) or tetraoctylammonium bromide (TOAB). For resorufin in NOP, the reorientation time constant increases with increasing electrolyte concentration, consistent with complexation between the resorufin anion and the electrolyte ammonium cation. We observe a qualitatively different trend in the aqueous resorufin solutions and understand these data for both solvent systems in the context of interactions between the chromophore and cationic species present.


A novel alternative splice domain in zebrafish tenascin-C.
We have identified and sequenced clones from a zebrafish library that correspond to tenascin-C (TN-C). The 2036-bp sequence covers the C-terminal segment of the protein. Comparison of this sequence to TN-C from other vertebrates indicates that our sequence starts in FN-III domain 5, continues with one alternative splice domain, then with FN-III domains 6-8 and, finally, the complete fibrinogen-like domain. The alternative splice domain, designated TNfnQ, is not closely identified to any of the domains in other species, and may represent a novel descendent of the alternative splice-domain precursor.


Cognitive, emotional, and neural benefits of musical leisure activities in aging and neurological rehabilitation: A critical review.
Music has the capacity to engage auditory, cognitive, motor, and emotional functions across cortical and subcortical brain regions and is relatively preserved in aging and dementia. Thus, music is a promising tool in the rehabilitation of aging-related neurological illnesses, such as stroke and Alzheimer disease. As the population ages and the incidence and prevalence of these illnesses rapidly increases, music-based interventions that are enjoyable and effective in the everyday care of the patients are needed. In addition to formal music therapy, musical leisure activities, such as music listening and singing, which patients can do on their own or with a caregiver, are a promising way to support psychological well-being during aging and in neurological rehabilitation. This review article provides an overview of current evidence on the cognitive, emotional, and neural effects of musical leisure activities both during normal aging and in the rehabilitation and care of stroke patients and people with dementia.


Effects of nitric oxide on the HPA axis and aggression.
We previously documented that male mice lacking the gene encoding the neuronal isoform of nitric oxide synthase (nNOS-/-) are more aggressive than wildtype (WT) mice in all standard testing paradigms. Testosterone is necessary, but not sufficient, to evoke the persistent aggression in these mutants. Deletion of the nNOS gene not only eliminates nNOS protein, but in common with many gene deletions, affects several 'down-stream' processes. For example, serotonin (5-HT) metabolism is altered in male nNOS-/- mice. Baseline corticosterone, but not ACTH, concentrations are also altered in the nNOS-/- mice. Despite elevated corticosterone concentrations, nNOS knockout mice are less 'anxious' or 'fearful' than WT mice, which may contribute to their aggressiveness. For example, male nNOS-/- mice spend more time in the open field than WT mice. Furthermore, nNOS knockout mice also show increased sensitivity to painful stimuli, which may also prolong aggressive interactions. Aggressive behaviour is not a unitary process, but is the result of complex interactions among several physiological, motivational, and behavioural systems, with contributions from the social and physical environment. The multiple, and often unanticipated, effects of targeted gene disruption on aggressive behaviour are discussed.


Tanshinone IIA Attenuates Contrast-Induced Nephropathy via Nrf2 Activation in Rats.
Tanshinone IIA is a chemical compound extracted from Salvia miltiorrhiza Bunge, a perennial plant also known as red sage used in traditional Chinese medicine. Tanshinone IIA has been shown to protect against various organ injuries. In this study, we hypothesized that Tanshinone IIA could play an anti-oxidative role in contrast-induced nephropathy (CIN) through enhancing Nrf2/ARE activation. To test whether Tanshinone IIA can attenuate CIN, oxidative stress, and apoptosis, we utilized two models: an in vivo Sprague-Dawley rat model of ioversol-induced CIN and an in vitro cell model of oxidative stress in which HK2 cells, a human renal tubular cell line, are treated with hydrogen peroxide (H2O2). Rats were randomly assigned to 4 groups (n = 6 per group): control group, ioversol group (ioversol-induced CIN), vehicle group (ioversol-induced CIN rats pretreated with vehicle), and Tanshinone IIA group (ioversol-induced CIN rats pretreated with 25mg/kg Tanshinone IIA). Renal functions, renal injuries and apoptosis were evaluated by using serum creatinine, histological scoring, and TUNEL staning respectively. Malondialdehyde, 8-hydroxy-2' -deoxyguanosine, and intracellular reactive oxygen species were used for oxidative stress assessment. Levels of Nrf2 and heme oxygenase-1 (HO-1) were measured in vivo and in vitro. Tanshinone IIA attenuated renal tubular necrosis, apoptosis and oxidative stress in rats and oxidative stress in HK2 cells. Furthermore, Tanshinone IIA activated Nrf2, and up-regulated HO-1 expression in vivo and in vitro, resulting in a reduction in oxidative stress. Tanshinone IIA may protect against CIN through enhancing Nrf2/ARE activation.


[The malunited distal radius fracture - early or late correction?].
BACKGROUND/GOAL: Despite the fact that corrective osteotomy for malunited distal radius fractures is widely accepted, the optimal timing is still a matter of controversy. The presented study compares the clinical and radiological results of early vs. late corrective osteotomy at the distal radius to evaluate the influence of timing. We prospectively studied 34 consecutive patients with extraarticular malaligned fractures of the distal end of the radius who underwent corrective osteotomy. Early correction was performed in 14 patients (10 -women and 4 men with an average age of 48±18 years) at an average of 8±3 weeks (range, 3-13) after the injury, late correction in 20 patients (16 women and 4 men, average age of 54±19 years) at an average of 52±46 weeks (range, 24-229) -after the injury. The demographic data of the groups were statistically identical. Preoperatively and at the recent follow-up the range of motion of the wrist (ROM) and grip strength were recorded as well as pain at rest and activity (visual analogue scale), DASH score and radiological data. A conclusive evaluation was performed by the modified Mayo wrist score for the recent follow-up after 24±10 (6-44) (early correction) vs. 21±10 (8-56) (late correction) months. All osteotomies healed uneventfully. Early corrections required significantly less bone-grafting. The comparison of the pre- and postoperative data in the early corrrection group showed an improvement of all parameters, that was significant in four parameters. The comparison of the pre- and postoperative data in the late correction group showed an improvement of all parameters, that was significant in 5 parameters. The comparison of the postoperative data revealed nearly identical results in both groups for all parameters including the modified Mayo wrist score. The general improvement stresses the value of both, early and late reconstruction. Although no statistical difference was detectable early corrective osteotomy seems to be recommendable in early presenting patients, in order to avoid bone-grafting. In later presenting cases we recommend observation and return after 6 months in the case of persistent pain or disability. Nevertheless, the time choice of corrective osteotomy remains an individual decision in all patients.


Sexual dimorphisms in a copulatory neuromuscular system in the green anole lizard.
Sexual dimorphisms in neuromuscular systems have been investigated in several vertebrate groups, but data on reptiles are limited. The present studies were designed to establish the copulatory neuromuscular system of the green anole lizard (Anolis carolinensis) as an appropriate model. Like mammals, male reptiles have copulatory organs. However, each individual has two "hemipenes" that are controlled by bilateral sets of muscles. First, the anatomy of the hemipenes and associated muscles was described in males and the same anatomical region examined in females. Second, spinal motoneurons innervating one of these muscles, the transversus penis (TPN), were localized by using the retrograde tracer biocytin. They were detected in the last trunk and first sacral segments (T17-S1). Third, motoneuron number and soma size were assessed in Nissl-stained sections of spinal cord segments T17-S1 of breeding males and females. Male-biased sexual dimorphisms were detected in both measures, but the motoneurons innervating a tail muscle, the caudifemoralis (CF), are also located in the same region of cord. Therefore, in the last study, the CF was injected with biocytin in both sexes to eliminate its motoneurons from the analysis and gain a more accurate representation of the TPN motoneuron pool. An equivalent number of CF motoneurons were labeled in both sexes, and the results from the previous study were replicated. Thus, similar to other vertebrate models, parallels between morphology and function exist in the green anole copulatory system. Future investigations will broaden the comparative perspective on mechanisms regulating sexual dimorphisms relating to reproductive behaviors in vertebrates.


Hypopyon uveitis (without scleritis) a manifestation symptom of relapsing polychondritis.
We report an atypical ocular symptom, hypopyon uveitis without scleritis encountered in relapsing polychondritis. Relapsing polychondritis should be considered in the differential diagnosis of sterile hypopyon uveitis.


The effect of chronic ethanol consumption on pathways of ethanol metabolism.
The contribution of the known hepatic pathways for the disposal of ethanol was studied utilizing two different experimental designs. In vitro studies were carried out in hepatocytes isolated from rats fed Purina chow. Rates of ethanol oxidation in these preparations increased with increasing levels of ethanol (10-50 mM). After inhibition of alcohol dehydrogenase (ADH) by pyrazole (2 mM) and the catalase by azide (1 mM) approximately 25% of the ethanol oxidizing activity remained. The residual activity was also dependent upon ethanol concentration and the apparent Km was 13 mM. Hepatocytes from ethanol-fed rats exhibited rates of ethanol oxidation which were also dependent upon the concentration of ethanol. The rates were higher in the hepatocytes from the ethanol-fed rats than in the controls. The addition of inhibitors of ADH and catalase lowered the rates, but abolished neither the differences nor the concentration dependency. In the in vivo studies, ethanol elimination rates were measured in alcohol-fed and control baboons by using a constant ethanol infusion to maintain blood ethanol at three different levels: 5, 10 or 50 mM. Ethanol elimination rate was accelerated with increasing concentration, particularly in alcohol-fed baboons. These observations indicate that a pathway other than the low Km alcohol dehydrogenase participates in alcohol oxidation and is responsible in part for the adaptive increase in ethanol metabolism associated with chronic ethanol consumption.


CNS disease following dissemination of SSPE measles virus from intraperitoneal inoculation of suckling hamsters.
Acute encephalitis was observed in suckling Golden Syrian hamsters following intraperitoneal (ip) inoculation of a hamster brain adapted strain of subacute sclerosing panencephalitis (SSPE) measles virus (HBS). Virus was isolated from the brains of all encephalitic animals by cocultivation of tissue with Vero cells. The histopathology of the encephalitis was characterized by perivascular mononuclear infiltrates, necrosis, eosinophilic inclusion bodies, and rare giant cells. Association of encephalitis with systemic viral infection was observed with virus present in lung and a kidney-spleen pool in addition to brain. Viral dissemination in asymptomatic animals was documented with virus being isolated from multiple non-neural tissues (spleen, lung, liver) of animals having no recoverable virus in their brains and no signs of encephalitis. Treatment of animals with cyclophosphamide prior to ip virus inoculation did not increase dissemination to brain. Absence of encephalitis in asymptomatic animals with proven viral dissemination to parenchymal organs indicates that neither viremia alone, nor viremia in conjunction with dissemination are sufficient conditions to establish central nervous system disease. The association of encephalitis with systemic viral infection and the dissemination to brain establish this model's potential value for the study of the pathogenesis of measles encephalitis.


[Psychiatric diseases in a small Alpine area--an epidemiologic field study].
Studies concerning the distribution of psychiatric diseases within a defined population are of fundamental importance for clinical psychiatry, public health projects and the development of strategies for mental health care. Each of the 1.337 inhabitants of an Alpine valley was psychiatrically recorded within a seven years period. The outcome of the presented field study carried out in a rural Tyrolean region reflects the real psychiatric morbidity. The primary and secondary data collecting indicated relevant psychopathological symptoms in 22,8 percent of the population of this small Alpine area. The given data are terms of reference for the planning of mental health care, and more than that, allow conclusions concerning causes, triggers, courses and consequences of psychiatric diseases.


A review of the genetic effects of ethyl methanesulfonate.
Ethyl methanesulfonate (EMS) is a monofunctional ethylating agent that has been found to be mutagenic in a wide variety of genetic test systems from viruses to mammals. It has also been shown to be carcinogenic in mammals. Alkylation of cellular, nucleophilic sites by EMS occurs via a mixed SN1/SN2 reaction mechanism. While ethylation of DNA occurs principally at nitrogen positions in the bases, because of the partial SN1 character of the reaction, EMS is also able to produce significant levels of alkylation at oxygens such as the O6 of guanine and in the DNA phosphate groups. Genetic data obtained using microorganisms suggest that EMS may produce both GC to AT and AT to GC transition mutations. There is also some evidence that EMS can cause base-pair insertions or deletions as well as more extensive intragenic deletions. In higher organisms, there is clear-cut evidence that EMS is able to break chromosomes, although the mechanisms involved are not well understood. An often cited hypothesis is that DNA bases ethylated by EMS (mostly the N-7 position of guanine) gradually hydrolyze from the deoxyribose on the DNA backbone leaving behind an apurinic (or possibly an apyrimidinic) site that is unstable and can lead to single-strand breakage of the DNA. Data also exist that suggest that ethylation of some chromosomal proteins in mouse spermatids by EMS may be an important factor in causing chromosome breakage.


Distractor interference stays constant despite variation in working memory load.
Previous studies have shown that working memory (WM) plays an important role in selective attention, sothat high WM load leads to inefficient distractor inhibition, in comparison with low WM load. In the present study, we examined the effect of WM on distractor processing while the extent of attentional focus was held constant. Our results show that WM load affected distractor processing only when it was positively correlated with the extent of attentional focus. When the latter was held constant, the effect ofWM became negligible. Furthermore, when low WM load was paired with a wide attentional focus and high WM load was matched with a narrow attentional focus, greater distractor processing was found when the WM load was low than when it was high. These results suggest that efficient distractor inhibition may require only minimal WM resources and that the effect of WM on distractor processing is more complex than has previously been assumed.


In Vivo Ovarian Cancer Gene Therapy Using CRISPR-Cas9.
Clustered regularly interspaced short palindromic repeats (CRISPR)-caspase 9 (Cas9) genome editing technology holds great promise for the field of human gene therapy. However, a lack of safe and effective delivery systems restricts its biomedical application. Here, a folate receptor-targeted liposome (F-LP) was used to deliver CRISPR plasmid DNA co-expressing Cas9 and single-guide RNA targeting the ovarian cancer-related DNA methyltransferase 1 (DNMT1) gene (gDNMT1). F-LP efficiently bound the gDNMT1 plasmid and formed a stable complex (F-LP/gDNMT1) that was safe for injection. F-LP/gDNMT1 effectively mutated endogenous DNMT1 in vitro, and then expressed the Cas9 endonuclease and downregulated DNMT1 in vivo. The tumor growth of both paclitaxel-sensitive and -resistant ovarian cancers were inhibited by F-LP/gDNMT1, which shows fewer adverse effects than paclitaxel injection. Therefore, CRISPR-Cas9-targeted DNMT1 manipulation may be a potential therapeutic regimen for ovarian cancer, and lipid-mediated delivery systems represent promising delivery vectors of CRISPR-Cas9 technology for precise genome editing therapeutics.


NT5E inhibition suppresses the growth of sunitinib-resistant cells and EMT course and AKT/GSK-3β signaling pathway in renal cell cancer.
We aimed to explore the mechanisms of sunitinib-resistance in renal cell cancer (RCC) and provide new therapeutic evidence and biomarkers for RCC treatment using human clear-cell renal cell carcinoma (ccRCC) cell line, 786-O. Microarray analysis, quantitative real time PCR (qRT-PCR), Western blot, and immunohistochemistry were used to detect Ecto-5'-nucleotidase (NT5E) expressions in sunitinib-resistant tissues in RCC. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, Thiazolyl Blue Tetrazolium Bromide (MTT), cell-count kit 8 (CCK-8), wound healing, and Transwell assays were used to investigate the influences of sunitinib and NT5E on 786-O cell line and sunitinib-resistant 786-O cell line (S786-O). Protein expressions related to epithelial-mesenchymal transition (EMT) and AKT/GSK-3β signaling pathway in 786-O cells and S786-O cells were determined by Western blot. In vivo experiment was performed using NCr-nu/nu mice to explore the effects of NT5E on cell growth and EMT signal in sunitinib environment. NT5E expression was upregulated in sunitinib-resistant RCC tissues and cells. NT5E downregulation repressed RCC cell proliferation, migration as well as invasion. EMT course and AKT/GSK-3β signal pathway both in vitro and in vivo in sunitinib environment was suppressed to varying degrees via NT5E inhibition. NT5E inhibition could suppress the growth of sunitinib-resistant RCC cells and restrain EMT course and AKT/GSK-3β signal pathway in sunitinib environment in RCC. © 2018 IUBMB Life, 71(1):113-124, 2019.


Amino-terminated supramolecular cucurbit [6] uril pseudorotaxane complexes immobilized on magnetite@silica nanoparticles: A highly efficient sorbent for salvianolic acids.
In this study, a novel amino-terminated supramolecular cucurbit [6] uril (CB [6]) pseudorotaxane motif coated magnetic nanoparticles (MNPs) was successfully fabricated through cucurbit [6] uril promoted azide-alkyne cycloaddition. The physicochemical properties of the obtained functional MNPs were investigated by scanning electron microscope, transmission electron microscope, energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, X-ray diffractometer, vibrating sample magnetometer, thermal gravimetric-derivative thermogravimetric analysis, and Zeta potential analyzer. Due to the abundant carboxyl groups in the structure of CB [6] and amino residue on the surface of the pseudorotaxane motif MNPs, the prepared materials were employed to extract salvianolic acids (SAs) for the first time. A series of significant parameters in the extraction and elution process, including sample pH, acetonitrile percentage, ionic strength and extraction temperature, as well as eluent type and desorption time, were examined systematically. Based on the results, the electrostatic interaction, van der Waals interaction, hydrophilic interaction and hydrogen bonding formation between the analytes and sorbent were speculated. The equilibrium state of static adsorption study indicated the outstanding adsorption capacity of pseudorotaxane motif MNPs toward six SAs to be 15-80 mg/g, providing much better adsorption affinity for SAs compared with MNPs only modified with amino, and their adsorption behaviors were all fitted with Freundlich adsorption isotherm model. In addition, the developed pseudorotaxane motif MNPs offered good recyclability and stability. Taking advantage of these merits, four SAs from Salvia miltiorrhiza Bunge were successfully extracted using the prepared pseudorotaxane motif MNPs with relative recovery in the range from 95.1% to 106.5% and RSDs below 9.7%. These results demonstrated that the synthesized pseudorotaxane motif MNPs showed potential as a candidate in the extraction of SAs.


Error assessment during "image guided" and "imaging interactive" stereotactic surgery.
The mechanical accuracy of several available stereotactic instruments is extremely high as measured in tests with rigid phantoms. The author's experience with stereotactic-guided resection by craniotomy using both "frameless" and framed methods simultaneously is that neither the image accuracy nor the mechanical accuracy of the instrument is the limiting factor in the usefulness of the guidance. Rather, it appears that the errors encountered in actual use have to do with tissue position changes which occur during the procedure. The accuracy may be better for extrinsic lesions rigidly attached to the skull, but for intrinsic lesions, tissue position changes occur following the release of cerebrospinal fluid, air entry into the subdural spaces, tumor debulking, or cyst drainage. The potential error appears to be worse with hydrocephalus, intraoperative dehydration, collapse of larger cysts, and debulking of large tumors. Even with very small intrinsic tumors in young, not atrophic patients, the error may be 5 mm. The need for intraoperative update of the guidance image is obvious if greater accuracy is required. The advantages of such "imaging-interactive" stereotactic surgery have long been apparent from stereotactic biopsy procedures performed in the CT scanner where errors such as needle deflection or hemorrhage can be appreciated and corrected promptly. With intraoperative scanning it is also possible to monitor the progress of a cyst aspiration and confirm the site of a biopsy to avoid unnecessary sampling in cases where the pathology is inherently equivocal.


Advantages of the high resolution melting in the detection of BRCA1 or BRCA2 mutation carriers.
The aim of the study is to explore the reliability of the high resolution melting (HRM) analysis for the identification of BRCA1/BRCA2 mutation carriers among the family members of index patient (IP) and for distinguishing the presence of two or more genetic variants within the same amplicon. We studied 27 different BRCA1/BRCA2 pathogenic mutations detected in 35 families with 194 subjects. HRM was performed in the LightCycler 480 (Roche). HRM method detected 110 BRCA1/BRCA2 mutations among the 192 relatives studied (57%). No false negative results were observed in any of the family members and all of them were in agreement with sequencing analysis, therefore the method might help to avoid unnecessary sequencing of wild type (WT) genotypes. The HRM method also allows the detection of other alterations that we initially had not searched (three unclassified variants and several polymorphisms). Furthermore, HRM has also been capable of distinguishing the presence of two or more genetic variants in the same amplicon of the same sample. HRM is a rapid, sensitive, specific, cost-effective and reliable screening method that in less than 2 h allows the easy identification of BRCA1 and BRCA2 genetic variations and also avoids the unnecessary sequencing of WT genotypes. Furthermore the method is also capable of detecting new genetic variants and allows the simultaneous detection of the presence of more than one genetic variant.


Effects of platelet activating factor on rat platelets in vivo.
Platelet activating factor (PAF) is not able to aggregate rat platelets in vitro. Due to the agonist effects of PAF on multiple cells, a possible role of PAF in the activation of rat platelets in vivo where different cells may influence each other was investigated. The pulmonary microembolization of 51Cr-labelled activated platelets was used as in vivo model. This model allowed us to monitor platelet behaviour by means of non-invasive methods. In contrast to results obtained in vitro, PAF activated rat platelets in vivo. The pulmonary microembolization of the platelets was dose-dependent and rapidly reversible. About 0.5 microgram/kg PAF caused a half-maximal rise of platelet-bound radioactivity in the thorax. Activation of the platelets by PAF was followed by extreme desensitization, so that a second injection of PAF did not provoke a significant response of the platelets. Platelet function was, however, not completely impaired because they still accumulated in the thorax after the application of ADP (50 micrograms/kg). That pulmonary entrapment had taken place was shown by a 3-fold increase in lung specific radioactivity. This was accompanied by a short-lasting thrombocytopenia. The PAF antagonist, WEB 2170 (30 micrograms/kg), significantly inhibited the microembolization of the platelets induced by PAF. Under in vitro conditions leukocytes purified from rat blood and activated by PAF were able to induce platelet aggregation. These results demonstrate that a PAF-specific activation of rat platelets is achievable in vivo which is probably mediated by other cells.


Selective coronary arteriography in congenitally corrected transposition of the great arteries.
Three cases of congenitally corrected transposition of the great arteries in adults who underwent selective coronary arteriography are presented. The morphologic features of the epicardial coronary anatomy are distinctive and are identifiable angiographically as morphologically right and left coronary arteries that are specifically concordant with the morphologically right and left ventricles. This relation is constant in the presented cases, in previously published coronary arteriograms of congenitally corrected transposition of the great arteries and in a review of the anatomic studies of congenitally corrected transposition of the great arteries that identify the coronary arterial pattern. Thus the angiographic characteristics of the epicardial coronary arterial pattern permit identification of the morphologic features of the underlying ventricle regardless of other spatial relations.


Immunopathological study of neuropeptide expression in human salivary gland neoplasms.
The immunoreactivity of anti-neuron-specific enolase (NSE) and anti-Leu-7 on formalin-fixed sections of human salivary gland neoplasms was determined by the avidin-biotin-peroxidase complex method. In addition, neuropeptides, such as vasoactive intestinal polypeptide, somatostatin, and substance P, in human salivary gland neoplasms were expressed, whereas other polypeptides, including glucagon, cholecystokinin, leu-enkephalin and calcitonin, were absent. When 182 paraffin-embedded examples of human salivary gland tumors, including 112 benign and 70 malignant neoplasms, were examined immunohistochemically, positive immunoreactivity was observed in: 51 cases with NSE (59%) and 46 cases with Leu-7 (54%) of 86 pleomorphic adenomas; 11 cases with Leu-7 (61%) of 18 Warthin's tumors; 7 cases with Leu-7 (58%) of 12 acinic cell carcinomas; 5 cases with NSE (31%) of 16 adenoid cystic carcinomas; 5 cases with NSE (42%) and 4 cases with Leu-7 (33%) of 12 adenocarcinomas; 4 cases with NSE (25%) and 6 cases with Leu-7 (38%) of 16 undifferentiated carcinomas. The other tumors, such as oxyphilic adenomas, basal cell adenomas, epidermoid carcinomas, and mucoepidermoid carcinomas, were nonreactive. Neuropeptides were observed in the neoplastic epithelial cells of certain tumors such as Warthin's tumors, acinic cell carcinomas, adenocarcinomas and undifferentiated carcinomas. These findings suggest the possibility that cells of neuroendocrine origin, present in certain neoplastic salivary gland epithelia may play a significant role in the histogenesis of human salivary gland neoplasms.


Ca2+ and H+ antagonize the decrease of [3H]MK-801 binding induced by glutamate and glycine in the presence of Mg2+.
We have studied the effects of various cations on [3H]MK-801 binding to N-methyl-D-aspartate (NMDA) receptors in membrane preparations of the rat cerebral cortex. Low concentrations of Tris, K+, Na+, Mg2+, and Ca2+ enhanced submaximally stimulated [3H]MK-801 binding. At high concentrations, all compounds inhibited [3H]MK-801 binding, possibly by a direct competitive effect. H+ decreased the observed association rate of [3H]MK-801 binding observed as a decreased [3H]MK-801 binding under nonequilibrium conditions, apparently by decreasing the sensitivity of the glutamate and glycine effects on the association rate. In addition, Tris, Na+, Mg2+, and possibly K+ at very high concentrations, permitted glutamate and glycine to decrease [3H]MK-801 binding, probably reflecting a decreased affinity of [3H]MK-801 binding. In contrast, Ca2+ and H+ antagonized these glutamate- and glycine-induced decreases of [3H]MK-801 binding observed in the presence of Mg2+, possibly by a direct competitive action on the permissive Mg2+ effect. These Ca2+ and H(+)-induced increases in [3H]MK-801 binding in the presence of Mg2+ may correspond to an increase in the potency of the Mg2+ block.


Pain in cognitively impaired older persons.
To summarize, there has been shamefully little empirical research directly examining the prevalence and correlates of pain among cognitively impaired older people. Even less is known about techniques for assessing and managing pain in this group. Existing evidence suggests that cognitively impaired older persons may voice fewer complaints about pain, but there is no reason to believe that they are in fact at less risk of pain than their cognitively intact age-mates. Rather, for whatever reason, persons with cognitively deficits appear to be less inclined to report pain than are intact elders of similar health status. This reporting difference may account at least in part for the fact that pain is less likely to be treated aggressively among cognitively impaired individuals. Unfortunately, knowing the reason for this state of affairs does not mitigate its implication: cognitive deficits place frail older persons at risk of unnecessary pain simply because it is not properly identified. Data reviewed in this chapter suggest that accurate assessment of pain in cognitively impaired older persons, far from being impossible, may actually be only slightly more demanding than it is in intact individuals. Even among markedly impaired elders, self-reports should certainly be taken as valid indicators; early evidence suggests promising avenues for developing reliable, clear-cut guidelines for the nonverbal assessment of pain in very severely demented individuals. As the nation grows older and medical care advances, a growing proportion of individuals can expect to live well into their eighth and even ninth decades. Unfortunately, with this extended life span comes increased likelihood of both cognitive impairment and pain. Thus, expansion of our repertoire of techniques for assessing and managing pain among cognitively impaired older persons must be a central priority for research on pain in late life.


Manic-depressive variant syndrome of childhood: a preliminary report.
The author describes the specific diagnostic entity of manic-depressive variant syndrome of childhood and outlines the five essential diagnostic criteria (affective storms, family history of significant affective dysfunction, hyperactivity, chronically disturbed personal relationships, and absence of psychotic thought disorder) and the five secondary criteria (sleep disturbances, minimal brain dysfunction, abnormal EEG, enuresis, and neuropathology). In the four cases reported, the children, when properly diagnosed, responded well to lithium therapy. The author points out the need for further study of this syndrome. Precautions about the use of lithium in children under age 12 are crucial, as is the need for continuing psychotherapy for parents and child.


Reduction of adverse events in MRI of the breast by personal patient care.
To determine the difference in anxiety reactions in patients undergoing standard (non-breast) magnetic resonance imaging (MRI) compared to breast magnetic resonance imaging (MRM) and to evaluate the influence of patient information before the breast imaging examination on the rate of premature termination of the procedure. Over 2 years, 5837 non-breast and 336 breast magnetic resonance examinations were performed at our institution. One group of breast MRM patients (n = 144) received detailed information and a second group (n = 189) received only routine information before MRI. The rates of premature termination were recorded for all groups. In 0.5% (27/5837) of patients undergoing standard MRI examinations the study had to be stopped prematurely. Of the breast MRM patients, those who had received only routine information had a significantly higher rate of premature termination when compared to the better-informed patients and those undergoing standard MRI (5.5%, 10/189, P= 0.01). A significantly lower rate of premature termination occurred in the better-informed breast group (0%, 0/144). MRM is associated with an increase in patient anxiety and higher rates of incomplete examination than other MR procedures. We recommend careful patient preparation including detailed verbal information before MRM and support during the procedure to obtain optimal patient compliance.


[Metabolic effects of indomethacin in irradiated rats].
The effect of indomethacin on serum glucose, insulin, thyroid hormones and corticosterone and on liver glycogen in 9 Gy whole body gamma irradiated rats was studied. In the first experimental setting indomethacin was administered subcutaneously in the dose of 4 mg/kg body weight 24 hours before irradiation and sham irradiation, and the analyses were done 48 hours after irradiation. In the second setting indomethacin was administered by the same route immediately, 24, 48, and 72 hours after exposure and sham exposure, the analyses were done 120 hours after irradiation. Control groups were treated with phosphate buffer. Indomethacin inhibited partially the radiation-induced increase in serum glucose and corticosterone in both settings and the increase in liver glycogen in the first one. Indomethacin administration had no effect on serum insulin levels, but it decreased serum thyroxine concentration in irradiated and non-irradiated rats in the second setting. The administration of indomethacin in irradiated animals is accompanied by various metabolic alterations.


Species composition of assemblages of Ceratomyxa (Myxozoa), parasites of lings Genypterus (Ophidiidae) in the southeastern Pacific Ocean: an ecomorphometric approach.
Studies on Myxozoa have emphasized their potential impact on aquatic animal health but less on ecological aspects. In this investigation, we assess the importance of host and latitudinal variations in the morphometry of spores of Ceratomyxa Théohan, 1892 (Myxozoa) from the gall bladder of 3 ling Genypterus (Pisces; Ophidiidae) species. Discriminant analyses indicated that several morphospecies of Ceratomyxa coexist in these hosts, despite the fact that the specific level of taxonomic resolution of each spore was not attempted. At least 4 species, i.e., Ceratomyxa hokarari Meglitsch, 1960; Ceratomyxa inversa Meglitsch, 1960; Ceratomyxa laxa Meglitsch, 1960; and Ceratomyxa elongata Meglitsch, 1960 occur in the study area, and at least 2 species co-occur in each host and geographical location. The most widespread pattern found is that spores are larger in golden ling (Genypterus blacodes) and spore size decreases with increasing latitude; this may be associated with the species composition of these assemblages, as well as with the habitat and diet segregation of the host species.


Interaction of the human serine protease inhibitor alpha-1-antitrypsin with Cryptosporidium parvum.
The protozoan parasite Cryptosporidium parvum was studied for interaction with a human serine protease inhibitor (serpin), alpha-1-antitrypsin (AAT). A C. parvum homogenate (CPH) prepared from oocysts was incubated with purified human AAT and complexes formed between the serpin and CPH were detected using an enzyme-linked immunosorbent assay (ELISA). The optical density read at 450 nm of AAT:CPH reactivity was significantly increased (P < 0.001) relative to CPH in the absence of AAT treatment. Additionally, ELISA reactivity was blocked by incubating AAT with a cognate target enzyme, porcine pancreatic elastase (PPE), prior to treatment of the CPH. Incubation of a partially excysted sample of C. parvum with AAT (37 C x 60 min) demonstrated preferential fluorescence labeling of sporozoites by indirect immunofluorescence assay; AAT complexes were not detected on intact oocysts. Localization of AAT interactions with C. parvum sporozoites was visualized by transmission immunoelectron microscopy. Collectively, these data suggest that C. parvum sporozoites express a protease-like component that is recognized by human AAT. The ability to block ELISA reactivity with PPE suggests that the AAT interactions we detected are functionally similar to the serpin-enzyme complex AAT forms with a protease target.


Adeno-associated viral vectors for clinical gene transfer studies.
Recombinant adeno-associated viral (rAAV) vectors can mediate the safe and long-term correction of genetic diseases in animal models following a single administration. These pre-clinical studies are the basis of human trials that have shown rAAV vector persistence and safety in humans following delivery to lung, sinus, skeletal muscle, brain and liver. Transient disease correction has also been demonstrated in humans treated for hemophilia B and cystic fibrosis using AAV2 vectors. The physiochemical properties of rAAV vector virions are amenable to industry accepted manufacturing methodologies, long-term storage and direct in vivo administration. Recombinant adeno-associated virus vectors are manufactured in compliance with current Good Manufacturing Practices (cGMPs) as outlined in the Code of Federal Regulations (21CFR). To meet these requirements, manufacturing controls and quality systems are established, including 1) adequate facilities and equipment, 2) personnel who have relevant education or experience and are trained for specific assigned duties, 3) raw materials that are qualified for use and 4) a process (including production, purification, formulation, filling, storage and shipping) that is controlled, aseptic, reliable and consistent. Quality systems including Quality Control (QC) and Quality Assurance (QA) are also implemented. These manufacturing procedures and quality systems are designed so the product meets its release specifications to ensure that patients receive a safe, pure, potent and stable investigational drug.


The role of ferroelectric domain structure in second harmonic generation in random quadratic media.
We study theoretically and numerically the second harmonic generation in a nonlinear crystal with random distribution of ferroelectric domains. We show that the specific features of disordered domain structure greatly affect the emission pattern of the generated harmonics. This phenomena can be used to characterize the degree of disorder in nonlinear photonic structures.


Evaluation of toxicological and antimicrobial activity of lavender and immortelle essential oils.
Lavender and immortelle essential oils (EOs) are widely used to treat a spectrum of human conditions. The aim of this study was to investigate cyto/genotoxic effects of lavender and immortelle EOs using plant cells (Allium cepa) and human lymphocytes, as well as their antimicrobial potential using nine strains of bacteria and fungi. Our results for lavender and immortelle EOs showed that the frequency of chromosome aberrations (CAs) was increased in comparison with controls. For both oils, increased frequency of apoptosis for all concentrations, as well as the frequency of necrosis (0.10/0.30 µl/ml for lavender/immortelle, respectively) was demonstrated. In human lymphocytes, differences for minute fragments between immortelle oil (0.10 µl/ml) and controls were observed. Increased frequency of apoptosis was detected for immortelle oil (0.20 µl/ml), while both oils (0.20; 0.30 µl/ml lavender, and immortelle at all concentrations) induced higher frequency of necrosis in comparison with controls. Lavender EO was effective against all tested Gram-positive and Gram-negative bacteria, while immortelle EO inhibited only Gram-positive bacteria. Both oils exhibited antifungal effect. Our results demonstrated that lavender and immortelle EOs showed cyto/genotoxic effects in both, plant and human cells, as well as antimicrobial properties. Further studies are needed to strengthen these findings.


Structure and molecular mobility of soy glycinin in the solid state.
We report a multitechnique study of structural organization and molecular mobility for soy glycinin at a low moisture content (<30% w/w) and relate these to its glass-to-rubber transition. Small-angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy are used to probe structure and mobility on different length and time scales. NMR (approximately 10(-6) to 10(-3) s) reveals transitions at a higher moisture content (>17%) than DSC or SAXS, which sample for much longer times (approximately 10 to 10(3) s) and where changes are detected at >13% water content at 20 degrees C. The mobility transitions are accompanied by small changes in unit-cell parameters and IR band intensities and are associated with the enhanced motion of the polypeptide backbone. This study shows how characteristic features of the ordered regions of the protein (probed by SAXS and FTIR) and mobile segments (probed by NMR and DSC) can be separately monitored and integrated within a mobility transformation framework.


Virus-ligand interactions: identification and characterization of ligand binding by NMR spectroscopy.
We demonstrate the detection and characterization of ligand binding to viruses via NMR. To illustrate the methodology, the interaction of an antiviral compound with human rhinovirus serotype 2 (HRV2) was investigated. Specific interaction of a capsid-binding inhibitor and native HRV2 was monitored utilizing saturation transfer difference (STD) NMR. STD NMR experiments at atomic resolution allowed those regions of the ligand that are involved in the interaction with the virus to be determined. The approach allows for (i) the fast and robust assessment of binding, (ii) the determination of the ligand binding epitope at atomic resolution without the necessity to crystallize virus-ligand complexes, and (iii) the reuse of the virus in subsequent assays. This methodology enables one to easily identify binding of drugs, peptides, and receptor or antibody fragments to the viral capsid.


Genetic studies on temperature-sensitive mutants of Bacillus subtilis bacteriophage SPP 1.
A total of 30 ts mutants of Bacillus subtilis bacteriophage SPP1 were isolated and subjected to complementation test. On the basis of this test 21 mutants were classified into 4 functional groups; the classification of the remaining 9 mutants was unclear. The frequency of recombination by mutual crossing was determined in representatives of individual groups; this made it possible to place these mutants on a linear map comprising a total length of 7.62 recombination units.