Therapy-related acute myeloid leukemia following radioactive iodine treatment for thyroid cancer.
Therapy-related acute myeloid leukemia (t-AML) associated with radioiodine treatment (RAI) is emerging as an important clinical entity with the rise in incidence of thyroid cancer. We conducted an electronic search of MEDLINE and EMBASE, and also searched reference lists of articles and abstracts from conference proceedings for case reports and review articles on t-AML following radioiodine therapy. A total of 37 patients with acute myeloid neoplasms following radioiodine treatment were analyzed. The median RAI dose was 324 mCi, and median age was 47.5 years with M/F ratio of 1:3. Latency period was 1-4 years, and the median time from RAI exposure to diagnosis of t-AML was 2.9 years. FAB M2 and M3 were the two most common t-AML subtypes reported. Seventy-one percent of the cases that reported cytogenetic abnormalities were classified as unfavorable. The most commonly reported abnormalities were del 5q and t(15:17). Survival outcomes were not reported due to lack of patient-level data. T-AML following radioiodine therapy for thyroid cancer appears to have a shorter latency period than other types of t-AML, which is an important consideration for post-therapy surveillance. Reporting of cases and outcomes will help provide data for further research. Identifying biomarkers that help risk-stratify patients prior to therapy and specific genetic-guided therapies may help improve outcomes.


Prevalence, incidence, deaths, and disability-adjusted life-years of drug use disorders for 204 countries and territories during the past 30 years.
Drug use disorders are increasingly recognized as the main cause of public health issues worldwide. The current analysis aims to provide the most comprehensive, updated estimates of the burden from drug use disorders at global, regional, and national levels during the past three decades. Prevalence, incidence, deaths, and disability-adjusted life-years (DALYs) were estimated from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 by age and sex for drug use disorder as well as its four main categories (opioid use disorders, cocaine use disorders, amphetamine use disorders, and cannabis use disorders) in 204 countries and territories between 1990 and 2019. DisMod-MR 2.1, and Bayesian meta-regression were used to analyze prevalence and incidence, while the Cause of Death Ensemble model (CODEm) was used to estimate death of diseases. Globally, the burden of drug use disorders, as measured by the average annual percentage change (AAPC) of deaths and DALYs, continues to increase. The patterns by regions of DALYs due to drug use disorders varied significantly, and it is mainly in developed countries and concentrated among young people and males. Programs for drug use disorders management should be improved, particularly in opioid use disorders. Governments will face increasing demand for treatment and support services, and effective prevention as well as control strategies are required to reduce the burden from these causes.


Redescription of Pinnixa haematosticta Sakai, 1934, its transfer to Indopinnixa Manning amp; Morton, 1987, and a reappraisal of Indopinnixa kumejima Naruse amp; Maenosono, 2012 (Decapoda: Brachyura: Pinnotheridae).
The poorly known pinnotherid crab, Pinnixa haematosticta Sakai, 1934, is redescribed on the basis of female holotype and additional specimens, including males and females, from Japan. The male characters of the species are documented for the first time. The species is transferred to Indopinnixa Manning Morton, 1987 because the male pleonal somites 35 are functionally fused, the telson is wide, and the maxilliped 3 with the dactylus is distinctly longer than the propodus. Indopinnixa kumejima Naruse Maenosono, 2012 is morphologically very similar to I. haematosticta n. comb., but a molecular phylogenetic analysis using partial fragments of the mitochondrial 16S rRNA gene supports the hypothesis that the two taxa as distinct. Morphologically, the two species are differentiated by the shape of the pereopod 4 merus (proportionally wider in I. haematosticta n. comb. than in I. kumejima). Our findings suggest that I. haematosticta n. comb. and I. kumejima are geographically distinct: I. haematosticta appears restricted to the Japanese mainland (Honshu to Kyushu) and Ohsumi Islands, while I. kumejima occurs in the Ryukyu and Ogasawara Islands.


The use of Mallory's phosphotungstic acid-hematoxilin (PTAH) stain in renal pathology.
High quality histology is needed in renal biopsy examination, especially when material for immunofluorescence and/or electron microscopy is not available. For these purposes Mallory PTAH stain was tried on 34 renal biopsies and the results were compared with the immunofluorescent and ultrastructural findings (used as a control of the reliability of the method). PTAH, besides showing extracellular structures, cytological details and rather subtle abnormalities, was able to detect the presence and the site of deposits. PTAH stains the material which appears as electron dense deposits in electron microscopy and as granular deposits in immunofluorescence, whereas it fails to stain linear deposits in immunofluorescence (which are not electron dense). Moreover, a good correspondence between PTAH and electron microscopic data was detected as far as the location of deposits is concerned.


In vitro cytotoxic drug sensitivity testing of human tumour xenografts grown as multicellular tumour spheroids.
Tumour cells from 7 patients with ovarian carcinoma and from 22 different human tumour xenografts representing a wide range of histological sub-types have been examined for multicellular spheroid forming ability. Spheroid formation was limited to cells derived from xenografts. Of the 22 lines tested, 5 formed spheroids capable of growth in isolation. There was no clear relationship between histological type and spheroid-forming ability. The plating efficiency of tumour cells obtained from spheroids was always greater than for the cells obtained from the dissociated tumour of origin and was in some cases as much as 6-fold greater. Spheroid growth was nearly exponential for 4 cell lines. Volume growth delay was used to investigate the activity of melphalan, adriamycin, the Vinca alkaloids, CCNU and cisplatin. Differences between lines in drug response broadly reflected patient and in vivo xenograft response.


Characterization of Borrelia burgdorferi associated antigens by monoclonal antibodies.
In this paper, we present a series of murine mAb recognizing B. burgdorferi antigens. The antibodies were characterized by immuno-blotting and immuno-fluorescence studies using isolates of B. burgdorferi from North America and Europe, respectively. Moreover, reactivity of the antibodies with recombinant B. burgdorferi flagellin and OspA was studied. The results suggest these anti-B. burgdorferi mAb as valuable tools for the serological analysis of B. burgdorferi isolates and for affinity-purification of the respective proteins. Moreover, these mAb appear suitable to classify antigenic variants of B. burgdorferi and to study the protective capacity of antibodies in a murine model for B. burgdorferi infection.


[Mechanisms of supralaryngeal airway obstruction in normal persons and habitual mouth breathers].
We examined oronasal flow partitioning in 27 volunteers with normal or slightly increased nasal resistance (mean +/- SD, 0.24 +/- 0.19 kPa/l/s). Mean percentage of inspiratory nasal flow contribution was measured during spontaneous oronasal breathing. The averaged nasal admixture of airflow differed considerably within and between all subjects (mean +/- SD, 20.9% +/- 16.5%; range 1%-70%), showing no correlation to nasal resistance. Five of 27 subjects with a history of habitual mouth breathing had a significantly lower nasal admixture as compared with controls (2.5% +/- 1.7% vs 25.1% +/- 15.4%; P less than 0.005), but with no statistical difference in nasal resistance. To evaluate the hypothesis that velopharyngeal narrowing is due to an increased tone of the soft palate, measurements were also performed under positive nasal pressure, inspiratory resistive loading at the mouth, and during breath-holding. There was no significant difference of airflow distribution between these modifications and unloaded breathing in either group. These data suggest, therefore, that oronasal flow distribution is due to active positioning of the soft palate, and that habitual mouth breathing without any nasal obstruction may be associated with closure of the velopharyngeal isthmus as a consequence of disturbed neural control mechanisms.


Short-Term Impact of Laparoscopic Cystectomy on Ovarian Reserve Tests in Bilateral and Unilateral Endometriotic and Nonendometriotic Cysts.
To evaluate the short-term changes in ovarian reserve markers after laparoscopic cystectomy performed for endometriotic and nonendometriotic cysts. Prospective case-control study (Canadian Task Force classification II-2). The Reproductive Endocrinology Clinic of a training and research hospital. Thirty-four women with endometrioma ≥ 4 mm (group 1) and 33 women with nonendometriotic cysts of matched size (group 2) who underwent surgery during the same period. The follicular phase follicle-stimulating hormone (FSH), estradiol (E2), and antimüllerian hormone (AMH) levels and the antral follicle count (AFC) of both groups were analyzed preoperatively and 2 months after laparoscopic cystectomy. The pre- and postoperative values were compared within the same group and between the 2 groups. Preoperative FSH and E2 levels were similar in both groups. However, preoperative AMH levels and AFC were significantly lower in group 1 (endometrioma) compared with group 2 (nonendometrioma; p = .004 and p = .025, respectively). In both groups there was a significant decrease in the AMH levels after surgery (3.1 ± 1.9 ng/mL to 2.5 ± 1.6 ng/mL, p < .001, and 5.7 ± 3.7 ng/mL to 4.8 ± 3.3 ng/mL, p = .04). AMH levels exhibited a significant decrease in the unilateral and bilateral endometrioma groups after cystectomy (p < .001 and p = .025, respectively). However, preoperative and postoperative changes in AMH and AFC were similar in groups 1 and 2 for both unilateral and bilateral cysts (p = .586 and p = .267). Preoperative AMH and AFC levels are lower in both unilateral and bilateral endometriomas compared with nonendometriotic cysts. The AMH levels decreased after cystectomy in both endometriotic and nonendometriotic cysts. However, in the short-term period the amount of change in ovarian reserve tests in both unilateral and bilateral cysts was similar for both endometrioma and nonendometriotic cysts.


Blood markers in remote ischaemic conditioning for acute ischaemic stroke: data from the REmote ischaemic Conditioning After Stroke Trial.
Remote ischaemic per-conditioning (RIC) is neuroprotective in experimental ischaemic stroke. Several neurohumoral, vascular and inflammatory mediators are implicated. The effect of RIC on plasma biomarkers was assessed using clinical data from the REmote ischaemic Conditioning After Stroke Trial (RECAST-1). RECAST-1 was a pilot sham-controlled blinded trial in 26 patients with ischaemic stroke, randomized to receive four 5-min cycles of RIC within 24 h of ictus. Plasma taken pre-intervention, immediately post-intervention and on day 4 was analysed for nitric oxide (nitrate/nitrite) using chemiluminescence and all other biomarkers by multiplex analysis. Biomarkers were correlated with clinical outcome (day 90 National Institutes of Health Stroke Scale, modified Rankin Scale, Barthel index). Remote ischaemic per-conditioning reduced serum amyloid protein (SAP) and tissue necrosis factor α (TNF-α) levels from pre- to post-intervention (n = 13, two-way ANOVA, p < 0.05). Overall (n = 26), increases in SAP pre- to post-intervention and pre-intervention to day 4 were moderately correlated with worse day 90 clinical outcomes. No consistent significant changes over time, or by treatment, or correlations with outcome were seen for other biomarkers. Remote ischaemic per-conditioning reduced SAP and TNF-α levels from pre- to post-intervention. Increases in plasma levels of SAP were associated with worse clinical outcomes after ischaemic stroke. Larger studies assessing biomarkers and the safety and efficacy of RIC in acute ischaemic stroke are warranted to further understand these relationships.


Separation of amino- and acetylamino-polycyclic aromatic hydrocarbons by reversed- and normal-phase high-performance liquid chromatography.
In the field of chemical carcinogenesis, amino- and acetylamino-polycyclic aromatic hydrocarbons (PAHs) are among the most studied compounds. Many of these compounds have recently been detected in the environment. Presently, knowledge permitting predictions of the high-performance liquid chromatographic (HPLC) retention order of amino- and acetylamino-PAHs, particularly among their geometric isomers is lacking. In order to obtain a better understanding of the separation of these types of compounds, we have studied the separation of a series of structurally related amino- and acetylamino-PAHs derived from naphthalene, phenanthrene, anthracene, pyrene, benz[a]anthracene, benzo[a]pyrene, and benzo[e]pyrene by using reversed-phase and normal-phase HPLC columns of different types (monomeric, polymeric, and chiral stationary phase). The results indicate: (i) Pirkle-type chiral stationary phase columns and the Zorbax SIL column can efficiently separate both the amino-PAHs and acetylamino-PAHs; (ii) in general, there was no correlation between retention time and molecular size; (iii) when acetylamino-PAHs were separated on the monomeric Zorbax ODS column, the isomer with the acetylamino group located at the carbon position of higher electron density has a shorter retention time; and (iv) separation of the parent PAHs was better than that of the amino-PAHs and acetylamino-PAHs. Our results thus may provide useful information for the analysis of amino-PAHs, particularly for distinguishing the geometric isomers of environmental samples.


Efficacy and safety of selamectin against gastrointestinal nematodes in cats presented as veterinary patients.
A series of randomized, controlled, masked, field (veterinary patient) studies were conducted in the USA and Europe to evaluate the efficacy of selamectin, a novel macrocyclic lactone of the avermectin subclass, in the treatment of naturally acquired gastrointestinal nematode infections in cats. After confirmation of ascarid and/or hookworm infection, 298 cats of various ages and breeds were randomly assigned to treatment with selamectin (n=202) or an existing commercially approved positive-control product (n=96). Unit doses of selamectin (providing a minimum dosage of 6mgkg(-1)) were administered topically to the skin in a single spot at monthly intervals. Quantitative fecal examinations were performed on days 0 (before treatment), 30, and 60. In the selamectin-treated cats, fecal ascarid egg counts were reduced by 99.6 to 100% on day 30, and by 99.9 to 100% on day 60. Fecal hookworm egg counts were reduced by 98.3% on day 30, and by 100% on day 60 in the selamectin-treated cats. The positive-control products achieved reductions in egg counts of 96.5 to 100% (ascarids) and 98.9 to 99.9% (hookworms). These studies have shown that monthly topical administration of selamectin is safe and highly effective in the treatment of naturally acquired ascarid and hookworm infections in cats.


Tourism-induced pollution emission amidst energy mix: evidence from Nigeria.
In recent years, there is concerted efforts to boost the tourism industry in Nigeria, and regulatory bodies were created for the tourism industry. This study is contributing to the ongoing debate on the tourism-energy-environment literature. Thus, we explore the linkage between tourism development, energy consumption, carbon dioxide (CO2) emission, and renewable energy consumption in Nigeria for the period of 1995-2016. The present study leverages on Bounds testing to cointegration in a carbon-income function environment while incorporating renewable energy consumption to the econometric framework. Subsequently, autoregressive distributed lag methodology alongside dynamic ordinary least square (DOLS) is utilized for robustness of estimations. Empirical results give credence to the energy-induced emission hypothesis in Nigeria. This outcome is suggestive to policymakers as fossil fuel-based energy consumption deplete the quality of the environment. Similarly, the study also affirms the environmental Kuznets curve (EKC) phenomenon. The emphasis on Nigerian growth trajectory (real income level) relative to her quality of environment via the channel of economic development and energy consumption from fossil-fuel source is indicated. On the other hand, renewable energy consumption in Nigeria shows significant ability to reduce emission level in Nigeria. This result is insightful, which implies that environmental quality is not threatened with an increase in tourist arrivals, hence tourism does not degrade the environment but is sustainable to the environment. Interesting and laudable for stakeholders' international tourism arrival did not deplete the quality of the environment. The plausible explanation is attributed to the scale of tourism in Nigeria which at the moment is still low or much more there is caution/awareness on ecotourism for sustainable environment.


A STUDY OF METHODS USED FOR DISINFECTION OF ANAESTHETIC EQUIPMENT BETWEEN TWO SURGICAL OPERATIONS AT A LARGE TEACHING HOSPITAL.
A prospective study on the growth of bacteria on certain commonly used anaesthetic equipment was undertaken in a large teaching hospital with a view to assess the effectiveness of disinfection/sterilization procedures. Samples for microbiological assessment were drawn by the worker using standardised procedures and tested in the laboratory by a microbiologist, blinded to the type of sample. Criteria for growth positivity was taken as > 25 colony forming units. A total of 90 observations were taken. 30 each for 'before use', 'after use' and 'after disinfection'. Overall 54.6% of the equipment showed growth "before use" with maximum growth being seen in Suction catheters (66.6%) and Guedal airways (60.0%). On the other hand, the proportion of equipment showing growth "after use" was quite high (84.6%), with suction catheters and endotracheal tubes showing 90.0% growth each. There was significant difference as regards "before" and "after" use growth on Endotracheal tubes, Guedel airways and Face masks (p < 0.05). Analysis of growth "after" disinfection" revealed that the probability of growth remains as high as 70% in suction catheters (95% CI=54% to 86%) and 60% in laryngoscopes (95% CI=43% to 78%). The study revealed gross inadequacies in methods of disinfection being followed at present.


Clinical Utility of Ultrasound-Guided Attenuation Parameter for the Detection and Quantification of Hepatic Steatosis in Patients with Fatty Liver Diagnosed by Computed Tomography.
This retrospective study was aimed (i) at elucidating the correlation between fatty liver diagnoses based on the plain computed tomography (CT) value and those based on the attenuation coefficient (AC) value determined with the ultrasound-guided attenuation parameter (UGAP) and (ii) at evaluating the diagnostic power of AC values. We included 125 patients who underwent blood tests, abdominal ultrasonography and abdominal CT at our department between April 2020 and March 2021. Hepatic fat infiltration was categorized as S0 (<5%), S1 (≥5 and 30<%), S2 (≥30 and <50%) or S3 (≥50%). The diagnostic ability of UGAP-determined AC was evaluated using receiver operating characteristic (ROC) curve analysis, and the correlation between AC value and fatty liver grade by CT value. The coefficient of correlation (r) between the AC value and plain CT value was -0.6188, indicating a moderate relationship. For diagnosing grade ≥S1 (n = 44), the area under the ROC curve (AUROC) was 0.8541, sensitivity 84.1%, specificity 81.5% and cutoff value 0.676 dB/cm/MHz. In diagnosing grade ≥S2 (n = 35), the AUROC was 0.8603, sensitivity 88.6%, specificity 81.1% and cutoff value 0.694 dB/cm/MHz. In diagnosing grade = S3 (n = 18), the AUROC was 0.9016, sensitivity 94.5%, specificity 81.9% and cutoff value, 0.704 dB/cm/MHz. The AC value is useful in diagnosing fatty liver.


Regulation of the cystic fibrosis transmembrane conductance regulator Cl- channel by specific protein kinases and protein phosphatases.
Cystic fibrosis transmembrane conductance regulator (CFTR) is a regulated Cl- channel; in secretory epithelia, it is located in the apical membrane where it regulates transepithelial Cl- secretion. Previous studies have shown that cAMP-dependent protein kinase (PKA) can phosphorylate and activate CFTR Cl- channels. We asked whether other kinases would phosphorylate CFTR in vitro and activate CFTR Cl- channels in excised, inside-out patches of membrane from NIH 3T3 fibroblasts stably expressing recombinant CFTR. We found that both Ca(2+)-independent and Ca(2+)-dependent isoforms of protein kinase C (PKC) activated the CFTR Cl- channel. Consistent with this finding, PKC also phosphorylated CFTR in vitro. In contrast, the multifunctional Ca2+/calmodulin-dependent protein kinase failed to either activate or to phosphorylate CFTR Cl- channels, suggesting that this enzyme has no direct effect on CFTR. We found that cGMP-dependent protein kinase (cGK) (purified from bovine lung) phosphorylated CFTR in vitro. However, cGMP failed to increase the apical membrane Cl- permeability in human airway epithelia, and addition of cGMP, ATP, and cGK failed to activate CFTR Cl- channels. These results suggest that if cGK phosphorylates CFTR in vivo, it does so at sites not involved in CFTR Cl- channel activation. Because cAMP-dependent activation of CFTR Cl- channels and Cl- secretion in intact cells is reversible, we asked whether specific phosphatases can dephosphorylate and inactivate CFTR Cl- channels. Addition of protein phosphatase 2A (PP2A) decreased PKA-activated current by 67% within 10 min. The phosphatase inhibitor calyculin-A blocked the effect of PP2A. In contrast, neither protein phosphatases 1, 2B, nor two preparations of alkaline phosphatase inactivated PKA-phosphorylated CFTR Cl- channels. The effects of protein phosphatases on CFTR function were paralleled by their ability to dephosphorylate CFTR in vitro. Our data indicate that CFTR Cl- channels can be phosphorylated and activated by PKA as well as by Ca(2+)-dependent and Ca(2+)-independent isoforms of PKC and can be dephosphorylated and thus inactivated by PP2A.


Equilibrium control of nonlinear verticum-type systems, applied to integrated pest control.
Linear verticum-type control and observation systems have been introduced for modelling certain industrial systems, consisting of subsystems, vertically connected by certain state variables. Recently the concept of verticum-type observation systems and the corresponding observability condition have been extended by the authors to the nonlinear case. In the present paper the general concept of a nonlinear verticum-type control system is introduced, and a sufficient condition for local controllability to equilibrium is obtained. In addition to a usual linearization, the basic idea is a decomposition of the control of the whole system into the control of the subsystems. Starting from the integrated pest control model of Rafikov and Limeira (2012) and Rafikov et al. (2012), a nonlinear verticum-type model has been set up an equilibrium control is obtained. Furthermore, a corresponding bioeconomical problem is solved minimizing the total cost of integrated pest control (combining chemical control with a biological one).


Functional and structural analysis of acetylcholine receptor-rich membranes after negative staining.
Phosphotungstate (pH 7.4) used for negative staining of membranes from Torpedo electric tissue rich in acetylcholine receptor does not affect binding properties and cation permeability of the receptor and its ion channel. Uranyl salts, frequently used for negative staining, precipitate the receptor-rich membranes making measurements of ligand binding and ion-permeability regulation impossible. The gross ultrastructure in the two stains is not significantly different, but for future high-resolution electron microscopy aiming at visualizing structural details of functional receptor molecules it is necessary to resort to a stain preserving native and active receptor. Uranyl salts are not applicable for this purpose. The electron micrographs obtained with phosphotungstate reveal two distinct structures in the receptor-rich membrane: a closed ring ('doughnut') and an open ring ('horseshoe'), with a ratio of abundance of about 3:2.


[Quality requirements for vitamins in the premix and nutritional supplements].
A comparison of the functions of vitamins included in the premixes and food additives has been carried out. The normative documentation regulating the quality parameters, hygienic safety requirements and their usage in the food industry has been analyzed.


Revision total knee arthroplasty with porous-coated metaphyseal sleeves provides radiographic ingrowth and stable fixation.
Porous-coated metaphyseal sleeves are designed to fill bone defects and facilitate osseointegration when bone loss in encountered during revision total knee arthroplasty (TKA). The purpose of this study is to evaluate short-term results of porous-coated metaphyseal sleeves with regards to implant fixation and clinical outcomes. A retrospective review was conducted on 50 patients (79 sleeves-49 tibial and 30 femoral) who had a press-fit metaphyseal sleeve with revision TKA. Tibial and femoral bone loss was classified according to the Anderson Orthopaedic Research Institute (AORI) bone defect classification. Post-operative complications of infection, revision surgery, and dislocation were assessed. Follow-up radiographs were evaluated for signs of loosening using the criteria developed by the Knee Society. The median follow-up was 58.8 months (range 25.8-93.0 months). The bone loss classifications were 1 type 1, 30 type 2a, 2 type 2b, and 17 type 3, and with regards to the femur, 5 were type 1, 8 type 2a, 31 type 2b, and 6 type 3. At final follow-up, 41/45 (91.1%) tibial and 28/29 (96.6%) femoral sleeves showed radiographic evidence of ingrowth. Of these 69 patients, all showed radiographic evidence of bony ingrowth. Three sleeves were revised for infection and two for loosening. The re-operation rate for loosening was 5/74 (6.8%) and for any reason was 14/74 (18.9%). Modular porous-coated press fit metaphyseal sleeves fill defects and provide evidence of radiographic ingrowth. Short-term stable fixation can be achieved with sleeves, which is helpful as more patients undergo revision total knee arthroplasty with greater bone loss. Longer duration studies are needed to ascertain the survival rate of these implants. IV.


The impact of uridine diphosphate-glucuronosyltransferase 1A9 (UGT1A9) gene promoter region single-nucleotide polymorphisms T-275A and C-2152T on early mycophenolic acid dose-interval exposure in de novo renal allograft recipients.
Mycophenolic acid (MPA), an effective immunosuppressive drug used in renal transplantation, is extensively glucuronidated by several uridine diphosphate-glucuronosyltransferases (UGTs) into an inactive 7-O-glucuronide and, to a lesser extent, into a pharmacologically active acyl-glucuronide. Experiments using human liver microsomes have shown that T--275A and C--2152T single-nucleotide polymorphisms (SNPs) of the UGT1A9 promoter region are associated with higher hepatic expression of UGT1A9 and increased in vitro glucuronidation activity for MPA. The distribution of UGT1A9 promoter region T-275A and C-2152T SNPs and the less frequent UGT1A9*3 coding region mutation, which results in decreased in vitro activity, was determined in 95 de novo renal recipients. The impact of these UGT1A9 SNPs on early clinical MPA pharmacokinetics was evaluated. Only in patients taking 2 g mycophenolate mofetil daily was a decreased MPA exposure observed in those who carried either the T-275 A or the C-2152 T polymorphism (or both) compared with those who did not (area under concentration-time curve [AUC] from 0 to 12 hours, 31.7+/--17.6 mg.h/L versus 63.6+/--30.9 mg.h/L [P=.009]; predose trough plasma concentration, 1.23 +/--.25 mg/L versus 2.84+/--1.64 mg/L [P=.04]). The partial MPA AUC from 6 to 12 hours (AUC6--12)-an estimate of MPA enterohepatic recirculation-and the ratio between partial MPA AUC6--12 and dose-interval AUC from 0 to 12 hours decreased when either or both UGT1A9 promoter region SNPs were present (AUC6--12, 6.2+/-5.4 mg.h/L versus 21.5+/-14.9 mg.h/L [P=.002]; ratio, 18.4%+/- 7.8% versus 31.7%+/- 8.8% [P=.002]). The T-275A and C-2152T SNPs of the UGT1A9 gene promoter are associated with significantly lower MPA exposure in renal recipients treated with 2 g mycophenolate mofetil daily, and part of this effect is caused by interruption of enterohepatic recirculation of MPA.


Head and neck squamous cell carcinoma is not associated with interleukin-18 promoter gene polymorphisms: a case-control study.
To investigate the association of two functional single nucleotide polymorphisms in the promoter region of the interleukin-18 gene, at positions -607 and -137, with head and neck squamous cell carcinoma. Genomic deoxyribonucleic acid was extracted, by the salting-out method, from peripheral blood leukocytes. Single nucleotide polymorphisms of the interleukin-18 gene at positions -607 (cytosine/adenine) and -137 (guanine/cytosine) were analysed by sequence-specific polymerase chain reaction. One hundred and eleven patients (86 men and 25 women; mean age 56.7+/-13.7 years) and 212 regional controls (165 men and 47 women; mean age 53.3+/-12.2 years) were studied. Control subjects comprised healthy volunteers or cancer-free individuals presenting with otolaryngological disease. The diagnosis of squamous cell carcinoma was confirmed histopathologically. Various clinical parameters were collected at diagnosis, including tumour site, tumour size, lymph node involvement, distant metastasis and stage. There was no significant association between the allele, genotype or haplotype frequencies of the two single nucleotide polymorphisms of the interleukin-18 promoter and the head and neck squamous cell carcinoma susceptibility or clinical parameters at diagnosis. Interleukin-18 polymorphisms at positions -607 and -137 did not confer susceptibility to head and neck squamous cell carcinoma in southern Iranian patients.


Characterization of the O-antigen gene clusters and development of a molecular serotyping method for Vibrio fluvialis.
Vibrio fluvialis is an emerging foodborne pathogen that causes severe infections. Serotyping based on surface polysaccharide antigens is important for the clinical detection and epidemiological surveillance of pathogens such as V. fluvialis. For example, variation of the O-antigen, which is highly polymorphic and is responsible for the majority of antigenic variability on the bacterial cell surface, provides the basis for serotyping of Gram-negative bacteria. Currently, there has been no analysis of the O-antigen gene clusters in V. fluvialis. In this study, the putative O-antigen gene clusters of 18 V. fluvialis serogroups (O1-O18), which exhibit a high level diversity, were analyzed by whole-genome sequencing. A microsphere-based suspension array (MSA) based on O-serogroup-specific genes was developed for identification of V. fluvialis strains O1-O18 and evaluated for specificity and sensitivity in double-blind tests. Furthermore, analysis of 62 publicly available V. fluvialis genomes identified 13 new O-antigen gene cluster types. The detection sensitivity was determined to be 10-2 ng for genomic DNA and 103 CFU for pure cultures. When testing simulated samples in an oyster background, 2 to 20 CFU per gram inoculated could be detected after enrichment using this method. Our work provides an efficient tool for rapid detection and identification of V. fluvialis serogroups from clinical and environmental samples, with the potential for use in epidemiological investigations and food safety applications.


Lobular carcinoma in situ of the breast: clinical, radiological, and pathological correlation.
The purpose of this study was to review the imaging findings associated with lobular carcinoma in situ (LCIS) of the breast with clinical and pathological correlation. A database search of patients treated at our institution from 2002 to 2011 identified 26 patients with LCIS associated with an imaging abnormality that had imaging available for review. LCIS was diagnosed by core-needle or excision biopsy. Patients subsequently underwent excisional biopsy, mastectomy, or clinical follow-up. Patients' mammography, ultrasonography (US), and magnetic resonance imaging (MRI) images were reviewed using the American College of Radiology Breast Imaging Reporting and Data System lexicon together with relevant clinical and pathology data. The 26 patients had 31 imaging lesions that yielded a histological diagnosis of LCIS by image-guided core-needle biopsy (n = 29) or excision biopsy (n = 2). Twenty-eight of 31 (90%) lesions yielding LCIS had a mammographic abnormality, 3/20 (15%) lesions had a US abnormality, and 6/7 (86%) had an abnormality on contrast-enhanced MRI. Calcifications were the most common mammographic finding, seen in 25/31 (80%) lesions. All three lesions seen on US were masses; the majority was irregular, hypoechoic, avascular, and had posterior shadowing. Non-mass-like enhancement was seen in five (71%) lesions with an MRI abnormality. Two (7%) patients developed subsequent malignancy at follow-up. LCIS can have associated imaging abnormalities, most commonly grouped amorphous calcifications on mammography, a shadowing, avascular, irregular, hypoechoic mass on US, or heterogeneous non-mass-like enhancement with persistent enhancement kinetics on MRI.


Synthesis and anticonvulsant properties of N-methylpyridyl derivatives of m- and p-bromophenylsuccinimides.
The reaction of m- or p-bromophenylsuccinic acids with 2-aminomethylpyridines yielded respective N-methylpyridylimides 1-8. Only compounds 1 and 6 show anticonvulsant activity in the pentetrazole and electric seizures tests, but their therapeutic index is inferior to that of ethosuximide and valproic acid.


Comparison of relative risks obtained in ecological and individual studies: some methodological considerations.
This paper is concerned with the problem of estimating relative risks from ecological correlation studies. In the first part, some of the biases encountered when analysing aggregated data are discussed and in particular attention is focused on the shape of the dose-response relationship obtained from aggregated and non-aggregated data, on the need for extrapolation and on the scale of aggregation. In the second part some empirical observations are made on these points by means of four examples concerning the relative risk between smoking and different pathologies. The estimates of relative risks derived from French geographical data and from case control or cohort studies are compared. The performance of ecological studies is discussed with respect to the strength of the risk factor considered, the geographical distribution of counfounding factors and the adjustment of different models.


Effects of perinatal exposure to delta 9-tetrahydrocannabinol on operant morphine-reinforced behavior.
The present study examined the effects of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) when administered during the perinatal period on morphine self-administration in adulthood. To this end, pregnant Wistar rats were daily exposed to Delta(9)-THC from the fifth day of gestation up to pup weaning, when they were separated by gender and left to mature to be used for analyses of operant food- and morphine-reinforced behavior in a progressive ratio (PR) schedule. We also analyzed dopaminergic activity (DOPAC/DA) in reward-related structures during specific phases of the behavioral study. In both reinforcement paradigms, food and morphine, females always reached higher patterns of self-administration than males, but this occurred for the two treatment groups, Delta(9)-THC or vehicle. These higher patterns measured in females corresponded with a higher DOPAC/DA in the nucleus accumbens prior to the onset of morphine self-administration in comparison to males. Interestingly, DOPAC/DA was lower in Delta(9)-THC-exposed females compared to oil-exposed females and similar to oil- and Delta(9)-THC-exposed males. In addition, Delta(9)-THC-exposed females also exhibited a reduction in DOPAC/DA in the ventral tegmental area, which did not exist in males. All these changes, however, disappeared after 15 days of morphine self-administration and they did not reappear after 15 additional days of extinction of this response. Our data suggest that females are more vulnerable than males in a PR schedule for operant food and morphine self-administration; perinatal Delta(9)-THC exposure is not a factor influencing this vulnerability. The neurochemical analysis revealed that the activity of limbic dopaminergic neurons prior to morphine self-administration was higher in females than males, as well as that the perinatal Delta(9)-THC treatment reduced the activity of these neurons only in females, although this had no influence on morphine vulnerability in these animals.


Immunostimulatory properties of ethylene-2,2' -bis(dithio)bis(ethanol) and related compounds in vivo.
ADA 202-718, as well as HEDS and higher homologues of ADA 202-718, were found to profoundly stimulate the delayed type hypersensitivity reaction in mice when given i.p. or orally in a dose range of 0.1 - 10 mg/kg. While even a single application of ADA 202-718 at the time of sensitization resulted in a stimulation of the hypersensitivity reaction, administration of the compound at the time of challenge was without effect. When ADA 202-718 was given to animals which were subjected to immunosuppressive therapy by cyclosporine, the suppressed hypersensitivity reaction was restored to normal. At much higher doses (50-200 mg/kg) ADA 202-718 enhanced the local graft-vs-host reaction in the rat. ADA 202-718 did not interfere with the suppressed graft-vs-host reaction obtained by immunosuppressive treatment with cyclosporine nor with the immunosuppressed skin transplant rejection. Single applications of HEDS or ADA 202-718 enhanced the humoral response of mice to sheep erythrocytes as well as to haptenized sheep or chicken erythrocytes. Although antibody levels at the time of maximal antibody production (day 4 for IgM) were only moderately enhanced, elevated antibody titres (IgM and IgG) were found even 23 days after sensitization. The age-dependent decreased humoral response of mice to sheep erythrocytes tended to be partially restored by twice weekly oral applications of HEDS or ADA 202-718 (0.1 to 1 mg/kg for 4 weeks). ADA 202-718 did not decrease the swelling in the Freund's adjuvant induced arthritis in the rat, but reduced the pain in this model. Swelling in a locally induced oedema was reduced in a dose-independent fashion. ADA 202-718 was more effective than acetyl salicylic acid in alleviating the oedema-associated pain.


Gastrin/CCK-ergic innervation of cutaneous mucous gland by the supramedullary cells of the puffer fish Takifugu niphobles.
The supramedullary cells (SMCs) are spinal neurons lying at the dorsal surface of teleosts. In the present study, we examined whether the SMCs of the puffer fish (Takifugu niphobles) might express gastrin/cholecystokinin-immunoreactivity, as observed in some other teleosts. All the SMCs were immunoreactive for gastrin/cholecystokinin. On the other hand, many immunoreactive varicose nerve fibers were also found terminating in the mucous glands in the skin. In addition, immunoreactive fibers were sparsely distributed in the epidermal layer. No neuronal cells other than the SMCs showed gastrin/cholecystokinin-immunoreactivity centrally or peripherally. The results suggest that gastrin/cholecystokinin-immunoreactive axons in the cutaneous mucous glands and epidermal layer are axons of the SMCs. In view of the present findings, the possible nature of SMCs was discussed.


Gold nanoparticles produce transient reactive gliosis in the adult brain.
Gold nanoparticles (GNPs) have unique physical and chemical properties that allow them to function as a drug-delivery system for several tissues: skin, eye, liver, and others. However, information about the biological response of brain tissue against GNPs is limited. Astrocytes and microglia cells are the first line of defense against brain insults and proper indicators of the level of brain damage. This study was aimed to evaluate the astrocytic and microglia response after an intracerebral injection of polyethylene-glycol-coupled GNPs (PEGylated GNPs). We injected spherical PEGylated GNPs (85 × 106 nanoparticles /nl) with a glass micropipette (inner diameter =35 μm) into the striatum of P60 CD1 mice. We evaluated the cellular response of astrocytes and microglia on days 3, 7, 14, 30, and 90 after intracerebral injection. For both astrocytes and microglia cells, our findings indicated that the glial response was transient and mainly circumscribed to the injection site. This evidence suggests that PEGylated GNPs are well-tolerated by the neural tissue. Understanding the effects of GNPs in the adult brain is a crucial step to design proper pharmacological vehicles to deliver long-lasting drugs.


Prenatal sonographic diagnosis of limb-body wall complex: case series of a rare congenital anomaly.
Three case reports of a rare congenital anomaly "limb-body wall complex" also known as "body stalk syndrome" are presented with prenatal ultrasonographic diagnostic features, immediate after delivery evaluation, and histopathologic analysis.


Distribution of pesticides and bisphenol A in sediments collected from rivers adjacent to coral reefs.
To investigate the deteriorating health of coral reefs in Okinawa, Japan, natural sediment samples were analyzed for diuron, Irgarol 1,051, chlorpyrifos, and bisphenol A (BPA) which are hazardous to corals. Samples were analyzed by solid-phase extraction (SPE) followed by high-performance liquid chromatography with tandem mass spectrometry (LC-MS-MS). Although diuron and chlorpyrifos usage is only well recorded for farms and not for cities, these chemicals were detected in both rural and urban areas. Additionally, diuron concentration in urban areas was in some cases higher than in rural areas, which might be caused by greater consumption of these chemicals in home gardens in city areas. Irgarol 1051 was detected in downstream river areas, which are situated far from the source sites such as pier or fishery harbor (0.6-3.2 km). This result suggested that Irgarol 1051 could be transported from the river mouths to the sampling sites during flood tides. High BPA concentrations were associated with urban areas (<1.2-22.0 microg kg(-1)), while low concentrations were associated with rural areas (nd-6.8 microg kg(-1)). The river sediments under study are delivered to coral reefs in large quantity through runoff caused by typhoons and other heavy rains. The highly hazardous chemicals are carried into coral reefs on these sediments. Therefore, these hazardous chemical substances may already be influencing the coral reefs.


Meso-dihydroguaiaretic acid isolated from Saururus chinensis inhibits cyclooxygenase-2 and 5-lipoxygenase in mouse bone marrow-derived mast cells.
Meso-dihydroguaiaretic acid (MDGA) is a medicinal herbal product isolated from the aerial parts of Saururus chinensis that inhibits the cyclooxygenase-2 (COX-2)-dependent phase of prostaglandin D(2) (PGD(2)) generation in bone marrow-derived mast cells (BMMC) (IC(50) 9.8 microM). However, this compound did not inhibit COX-2 protein expression in BMMC at concentrations up to 30 microM, indicating that MDGA directly inhibits COX-2 activity. In addition, this compound consistently inhibited the production of leukotriene C(4) (IC(50) 1.3 microM). These results demonstrate that MDGA inhibits both COX-2 and 5-lipoxygenase. Furthermore, this compound strongly inhibited the degranulation reaction in BMMC (IC(50) 11.4 microM). Therefore, this compound might provide a basis for novel anti-inflammatory drug development.


A tandem-repeat galectin-4 from Nile tilapia (Oreochromis niloticus) is involved in immune response to bacterial infection via mediating pathogen recognition and opsonization.
Galectins are the family of carbohydrate-binding proteins that participate in host-pathogen interaction. In this study, a galectin-4 homolog (OnGal-4) from Nile tilapia (Oreochromis niloticus) was characterized. The open reading frame of OnGal-4 was 1194 bp, encoding a peptide of 397 amino including two CRD regions and two carbohydrate recognition sites. OnGal-4 mRNA was expressed in all examined tissues with the highest level in spleen. After Streptococcus agalactiae (S.agalactiae) challenge, the OnGal-4 expression was up-regulated in the spleen, head kidney, brain, and monocytes/macrophages (Mo/MΦ). The in vitro experiments showed that recombinant OnGal-4 (rOnGal-4) protein could bind and agglutinate S.agalactiae and A.hydrophila. Also, rOnGal-4 could induce cytokines expressions and increased bactericidal activity of Mo/MΦ. Further in vivo analysis indicated that OnGal-4 overexpression could protect O.niloticus from S.agalactiae infection through modulating inflammation response. Our study suggested that OnGal-4 could improve immune response against bacterial infection by mediating pathogen recognition and opsonization.


Sedation and analgesia in paediatric intensive care units: a guide to drug selection and use.
The indications for sedation in the paediatric intensive care unit (PICU) patient are varied ranging from short term use for various procedures to prolonged administration to provide comfort during mechanical ventilation. When faced with the decision to institute sedation, the healthcare provider must make three decisions: the agent to be used, the route of delivery, and the mode of administration (intermittent versus continuous). There are several agents that have been used to provide sedation in the PICU patient including the inhalational anaesthetic agents, benzodiazepines, opioids, ketamine, propofol, chloral hydrate, phenothiazines, and the barbiturates. This review describes the various agents for sedation and discusses their advantages and disadvantages as they pertain to the PICU. Consequences of and treatment strategies for long term problems with prolonged sedation including tolerance, physical dependency, and withdrawal are reviewed.


N-acetyltransferase-2 gene polymorphisms and prostate cancer susceptibility in Latin American patients.
We investigated the role of N-acetyltransferases (NAT) in prostate cancer (PCa) susceptibility. NAT are polymorphic in the population and metabolize important carcinogenic products directly involved in the tumor initiation process. This prospective case-control study utilized the polymerase chain reaction-based restriction fragment length polymorphism method and comprised a cohort of consecutive 478 individuals: 126 men with prostate cancer; 101 men with benign prostatic hyperplasia (BPH); and a control health population of 177 female and 74 male blood donors from the same region. NAT2 slow or fast acetylators genotypes were determined by the combination of four variant alleles. Lifetime occupational history, dietary patterns, cigarette smoking and other anamnestic data were obtained by interviews. We were not able to find any correlation among smoking, dietary patterns, parameters of tumor aggressiveness or patient outcome and any NAT2 genotypes or phenotypes considered in separate or in different combinations. However, there was an association between NAT2T481C (OR=0.47; 95% CI=0.26-0.84; P=0.01) and NAT2A803G (OR=0.57; 95% CI=0.33-0.97; P=0.04) polymorphisms and PCa protection. Conversely, the presence of NAT2G857A genotype increased the risk of PCa more than 3 times (OR=3.57; 95% CI=1.39-9.15; P=0.005). Slow acetylator NAT2*7A and NAT2*6B genotypes occurred in 10.31% of PCa but in none of BPH patients (P=0.0007). The control health population confirmed the results and allowed the exclusion of possible biases caused by gender influence on genotype inheritance and by the inclusion of not diagnosed prostate diseases patients among the control individuals. We suggest that the investigation of germline polymorphisms of NAT2 gene may be useful in the assessment of Latin American patients at risk of BPH and PCa.


Expression of beta-catenin, E-cadherin and APC in canine mammary tumors.
Mammary tumors are a very common neoplasm in the dog and show histological features and biological behaviour similar to human mammary carcinomas. Recently, a pathway named Wnt-1, involving beta-catenin and APC protein, has emerged as an important player in many human tumor types, including mammary neoplasms. Thirty-five samples of canine mammary tumors (10 benign and 25 malignant) were studied in order to evaluate the co-expression of beta-catenin, APC protein and E cadherin with confocal laser microscopical observation, by western blot analysis and by correlating data obtained with the histological grade of tumours. A progressive decrease of E-cadherin together with disruption of beta-catenin expression was observed in less differentiated malignant tumors. In addition, a loss of beta-catenin membranous distribution and a cytoplasmic accumulation was often coexpressed with disrupted expression of APC protein. Western blot analysis showed a progressive increase of beta-catenin in malignant tumors, which could be the expression of disrupted /-catenin catabolism leading to cytoplasmic accumulation. In some less differentiated malignant tumors, a marked beta-catenin decrease was also observed. This feature could be linked to mutations in beta-catenin gene coding for a truncated and lighter protein. These results may indicate the multifunctional role played by beta-catenin in canine mammary oncogenesis.


[Information campaigns in the fight against tuberculosis until about 1940].
Already before the advent of vaccination and antibiotics in Norway in the 1940s, mortality from tuberculosis was heavily reduced. Initiatives from central and local authorities, the efforts of housewives in the homes and the activity of voluntary organizations were attempts to obtain this result. This article focuses on information campaigns staged by the National Association Against Tuberculosis between 1910 and 1920. Annual reports from the National Association, the Association's journal, the archive from the Lyster Sanatorium in the Bergen Town Archives, and earlier literature on this theme. The Association Against Tuberculosis organised extensive information campaigns through lectures, leaflets, its journal, and "travelling teachers", targeting the general public as well as defined groups. Men were especially admonished to stop spitting, women to keep the home clean, and patients to follow doctor's instructions. The information campaigns were part of comprehensive efforts made by voluntary organizations, public authorities, doctors and housewives to reduce the mortality of tuberculosis before the advent of vaccination. Higher standards of living also contributed to goal attainment.


Heme precursor 5-aminolevulinic acid alters brain tryptophan and serotonin levels without changing pineal serotonin and melatonin concentrations.
The daytime administration of the heme precursor 5-aminolevulinate (5-ALA) has been shown to reduce brain tryptophan and serotonin levels owing to saturation of liver tryptophan pyrrolase. Saturation of this enzyme with heme results in enhanced activity, leading to increased catabolism of tryptophan and thus making less tryptophan available to the brain. Tryptophan is also the precursor of melatonin, a primary secretory product of the pineal gland. Reduced melatonin levels, which could be a consequence of altered tryptophan metabolism, have been associated with depressive disorders in humans. In view of this, in the present study we examined the effects of 5-ALA administration on forebrain tryptophan and serotonin levels as well as pineal serotonin, melatonin, and the pineal melatonin-forming enzymes N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT). 5-ALA induced a reduction in forebrain tryptophan and serotonin levels during the light phase and caused the opposite effect in the dark phase. Allopurinol, an inhibitor of hepatic tryptophan pyrrolase activity, prevented the reduction in the indole levels induced by 5-ALA. Although 5-ALA induced these changes in the forebrain, it did not alter either daytime or nighttime pineal NAT, HIMOT, serotonin, or melatonin levels. It appears that high serotonin levels and melatonin production in the pineal are conserved even in the face of low circulating tryptophan levels, changes which alter brain tryptophan and serotonin concentrations.


Interface inflammation after laser in situ keratomileusis. Sands of the Sahara syndrome.
To determine the source of the interface debris that causes the interface inflammation known as "sands of the Sahara" after laser in situ keratomileusis (LASIK). Department of Ophthalmology, LSU Eye Center, Louisiana State University Medical Center School of Medicine, New Orleans, USA. A microkeratome (Automated Corneal Shaper) was used to make a LASIK flap in 8 eyes of 4 rabbits. In 4 eyes, the blade was used directly from the sterile pack; in the contralateral 4 eyes, the blade was cleaned prior to use. In vivo confocal microscopy of the corneas was performed 1 day after surgery. An unused, cleaned blade and an unused, uncleaned blade, as well as blades used in the rabbit eyes, were examined by scanning electron microscopy. Confocal microscopy revealed numerous fragments of debris surrounded by inflammatory cells in the LASIK flap interfaces created by blades taken directly from the sterile package. Interfaces created by the cleaned blades showed only rare, scattered bits of debris. Scanning electron microscopy of the unused blades showed debris on the uncleaned blade removed directly from the sterile package. Post-LASIK interface inflammation may be caused by debris on the microkeratome blade, although other sources are possible. The interface debris and inflammation can be reduced or eliminated by cleaning the microkeratome blade before use.


The molecular assembly of amyloid aβ controls its neurotoxicity and binding to cellular proteins.
Accumulation of β-sheet-rich peptide (Aβ) is strongly associated with Alzheimer's disease, characterized by reduction in synapse density, structural alterations of dendritic spines, modification of synaptic protein expression, loss of long-term potentiation and neuronal cell death. Aβ species are potent neurotoxins, however the molecular mechanism responsible for Aβ toxicity is still unknown. Numerous mechanisms of toxicity were proposed, although there is no agreement about their relative importance in disease pathogenesis. Here, the toxicity of Aβ 1-40 and Aβ 1-42 monomers, oligomers or fibrils, was evaluated using the N2a cell line. A structure-function relationship between peptide aggregation state and toxic properties was established. Moreover, we demonstrated that Aβ toxic species cross the plasma membrane, accumulate in cells and bind to a variety of internal proteins, especially on the cytoskeleton and in the endoplasmatic reticulum (ER). Based on these data we suggest that numerous proteins act as Aβ receptors in N2a cells, triggering a multi factorial toxicity.


[Surgical repair of coronary sinus type partial anomalous pulmonary venous drainage with intact atrial septum].
We experienced a rare form of PAPVD without atrial septal defect. The patient was a 33-year-old male and he was referred to our institute because of mild right pulmonary congestion detected by a routine chest X-P. Enlarged coronary sinus, right atrium and right ventricle were documented by UCG. The Qp/Qs was 1.9 and pulmonary artery pressure was 38/7 mmHg (mean: 17 mmHg) by cardiac catheterization. Selective pulmonary angiogram showed that all right pulmonary veins drained into the coronary sinus without evidence of an atrial septal defect. Enhanced chest CT clearly demonstrated the connection between the right pulmonary vein and the coronary sinus. Intracardiac repair without atrial baffle was carried out under hypothermic cardiopulmonary bypass. Under cardiac arrest with cardioplegia, the common wall between the right pulmonary vein and the left atrium was incised and the connection between the right pulmonary vein and the left atrium was established. The flap made by this incision was brought posterior to close the right pulmonary vein opening to the coronary sinus. The postoperative course was uneventful and the minimum diameter of the right pulmonary vein was found to be 15.5 mm by a postoperative pulmonary artery angiogram. This operative method without an atrial baffle could be an alternative procedure for coronary sinus type PAPVD.


Normal pregnancies and live births after autograft of frozen-thawed hemi-ovaries into ewes.
To evaluate long-term outcome of autotransplantation of cryopreserved hemi-ovaries into ewes. Animal study. University fertility center, Hospices Civils de Lyon; and Ecole Nationale Vétérinaire de Lyon. Grivette ewes. Six hemi-ovaries from 6 ewes aged 6 to 12 months were frozen with a slow cooling protocol using 2 M of dimethyl sulfoxide as cryoprotectant. After dissection of the medulla, the hemi-ovarian cortex was stored at -196 degrees C in liquid nitrogen. Freezing procedure was performed with a programmable freezer. Semiautomatic seeding was performed before crystallization. Four to 6 weeks after the first laparotomy, the left ovary was removed and the frozen-thawed hemi-ovary was sutured. Mean plasma concentrations of FSH, LH, and progesterone after autotransplantation of frozen-thawed hemi-ovary. Ultrasonography was done to confirm pregnancy. Blood samples were collected weekly to measure FSH, LH, and progesterone. After the first birth, the autografted ovary was removed for histologic examination. Plasma progesterone concentration increased in a regular manner in all ewes except one 4 weeks after the graft. Concentrations of FSH and LH did not reach the menopausal level. Four pregnancies occurred, from which 6 lambs were born. The first delivery of a normal lamb occurred after 135 days of gestation; the lamb died immediately after birth. The second delivery of two normal lambs occurred after 130 days of gestation. A caesarean section was performed on the third pregnant ewe the 110th days of gestation because the ewe had a vaginal prolapsus. The two normal lambs and the ewe died after surgery. The fourth birth of a normal lamb occurred after 132 days of gestation. Histologic examination of the grafted frozen-thawed ovary showed a regressing corpus luteum and few primordial and antral follicles. These four pregnancies in a ewe model may indicate that women who undergo preservation of their ovaries before chemotherapy or radiotherapy can have successful pregnancy.


Is mediastinal shift on chest X-ray of pneumothorax always an emergency?
To determine the incidence of mediastinal shift on chest X-ray due to pneumothorax. A retrospective chart review was undertaken of all patients with pneumothorax presenting to the ED over the period 1 January 1995 to 31 December 1999. The primary outcome was mediastinal shift on initial CXR. The incidence of clinical tension pneumothorax was noted. There were 176 presentations with pneumothorax in the study period. Two cases of clinical tension pneumothorax were identified and treated prior to CXR. Thirty patients with mediastinal shift on initial CXR, none of which clinically merited emergency needle decompression, were all managed with intercostal catheter (ICC) insertion. Overall, 141 of 176 (80.1%) had an ICC inserted as part of their management. Mean pulse rate (91.8 SD 29.5 vs 86.7 SD 23.6, P = 0.02) and respiratory rate (21.9 SD 14.4 vs 15.1 SD 11.5, P = 0.03) were greater in patients with mediastinal shift on CXR. True clinical tension pneumothorax is an uncommon condition. Radiological evidence of mediastinal shift is more common. No patient in this latter group deteriorated while awaiting X-ray.


Photodynamic therapy with local photosensitizer delivery inhibits experimental intimal hyperplasia.
Photodynamic therapy (PDT), the light activation of photosensitizer dyes for the production of free radicals, effectively inhibits experimental intimal hyperplasia with systemic administration of the photosensitizer. The local application of the photosensitizer directly into a vascular lesion to avoid systemic side effects and tightly control dose administration has theoretical appeal. The aim of this study was to quantify serum and arterial tissue uptake after site-specific photosensitizer delivery and, following PDT, determine its effectiveness at inhibiting intimal hyperplasia. The rat common carotid artery was balloon-injured, pressurized at 400 mm Hg for 2 minutes with the photosensitizer dye benzoporphyrin-derivative (BPD), and irradiated with 690 nm laser light at a fluence of 100 J/cm2. Control animals were pressurized with saline only, or received no additional treatment than balloon-injury. Pressurization with BPD resulted in complete penetration of the intima and media and was associated with relatively high tissue, but almost no detectable serum BPD concentrations. No skin photosensitization or other systemic side effects were observed with photosensitizer administration. After 9 days, PDT-treated arteries displayed a significantly lower number of smooth muscle cells in the arterial wall than balloon-injured (P < 0.001) or saline-pressurized arteries (P < 0.0002), and no intimal hyperplasia. At 21 days, IH after PDT was significantly reduced as compared with balloon-injured (P < 0.0004), or saline-pressurized arteries (P < 0.003) with no arterial dilatation. Site-specific delivery of liposomal BPD followed by PDT represents a safe method to treat arteries, and may be effectively used in vivo to inhibit the development of intimal hyperplasia.


Effect of some pesticides on certain micro-organisms, contributing to soil fertility.
A pot experiment was run for studying the effect of Temik (insecticide and nematocide), Orthocide (fungicide), and Treflan (herbicide) on certain desirable soil micro-organisms. Total counts of bacteria, actinomycetes or fungi were mostly lower in the treated than in the untreated soil. Aerobic cellulose-decomposers were either stimulated or depressed. Despite the temporarily slight stimulation, observed in some instances at the initial periods, the effect of the pesticides on counts of Azotobacter, N-fixing clostridia, and ammonifiers was afterwards depressed. The period of retardation or stimulation differed according to type of pesticide and type of micro-organisms under study. However, the autotrophic nitrifying bacteria, especially ammonium-oxidizers, seemed to be more sensitive and their counts in treated soil were sharply depressed.


Treatment of MRI-Diagnosed Trigeminal Peripheral Nerve Sheath Tumors by Stereotactic Radiotherapy in Dogs.
Stereotactic radiotherapy (SRT) is an emerging technique for treating tumors in animals. To assess the outcome of dogs with suspected intracranial trigeminal nerve peripheral nerve sheath tumors (PNST) treated with SRT. Eight dogs with presumptive PNST. This was a retrospective study of dogs identified by searching UC Davis Veterinary Medical Teaching Hospital medical records for dogs treated with SRT for a presumed PNST. Presumptive diagnosis was based on magnetic resonance imaging. SRT was delivered in 3 dose fractions of 8 Gray (Gy) on consecutive days or every other day to a total dose of 24 Gy. Median disease-specific survival was 745 days (range: 99-1375 days, n = 6). No signs of acute adverse effects of radiation treatment were recorded. Late radiation effects versus tumor progression could not be confirmed histopathologically because of few animals undergoing necropsy. This study provides preliminary evidence that dogs with PNST benefit from SRT in terms of long-term survival. The treatment appears to be well tolerated and requires fewer anesthetic events for animals compared to full-course radiation.


First evidence of cytochrome P-450 induction in the mouse brain by phenytoin.
Long-term administration of phenytoin (60 mg/kg) to male C57Bl/6J mice causes an average drug serum level of 16-19 micrograms/ml. Cytological changes consisting of focal axonal swellings in the deep cerebellar nuclei are characterized by an increasing accumulation of vesiculotubular membranes in the dense, but ribosome-deficient axoplasm. Microsomal fractions of brain and liver were prepared at intervals until the 80th day of treatment to determine their cytochrome P-450 activities and isoenzyme characteristics. The cerebellar tissue was shown to be distinguished by a 15-fold enhancement of cytochrome P-450 PB3a activity, that means twice the extent of that found in liver and cerebrum.


Implementation of permeation rules leads to a FabI inhibitor with activity against Gram-negative pathogens.
Gram-negative bacterial infections are a significant public health concern, and the lack of new drug classes for these pathogens is linked to the inability of most drug leads to accumulate inside Gram-negative bacteria1-7. Here, we report the development of a web application-eNTRyway-that predicts compound accumulation (in Escherichia coli) from its structure. In conjunction with structure-activity relationships and X-ray data, eNTRyway was utilized to re-design Debio-1452-a Gram-positive-only antibiotic8-into versions that accumulate in E. coli and possess antibacterial activity against high-priority Gram-negative pathogens. The lead compound Debio-1452-NH3 operates as an antibiotic via the same mechanism as Debio-1452, namely potent inhibition of the enoyl-acyl carrier protein reductase FabI, as validated by in vitro enzyme assays and the generation of bacterial isolates with spontaneous target mutations. Debio-1452-NH3 is well tolerated in vivo, reduces bacterial burden in mice and rescues mice from lethal infections with clinical isolates of Acinetobacter baumannii, Klebsiella pneumoniae and E. coli. This work provides tools for the facile discovery and development of high-accumulating compounds in E. coli, and a general blueprint for the conversion of Gram-positive-only compounds into broad-spectrum antibiotics.


Long-Term Outcomes of Catheter-Directed Thrombolysis for Acute Lower Extremity Occlusions of Native Arteries and Prosthetic Bypass Grafts.
Catheter-directed thrombolysis is a well-accepted treatment for acute lower extremity occlusions of native arteries and bypass grafts. Several variables that affect outcomes of thrombolysis have been identified. The hypothesis of this study was that the long-term outcome after catheter-directed thrombolysis would be better for acute lower extremity occlusions of native arteries compared with prosthetic bypass grafts. This observational study retrospectively analyzed 159 consecutive patients (114 men), median age, 65 years (range 57-73 years), with 89 native artery (56%), and 70 prosthetic bypass graft (44%) occlusions of the lower extremity. All patients were treated with catheter-directed thrombolysis between 2006 and 2009 in 2 vascular referral centers in the Netherlands. The severity of ischemia was Rutherford class I (52%), class IIa (27%), class IIb (12%) and unknown (9%) in native arteries and class I (64%), class IIa (19%), class IIb (1%), and unknown (16%) in bypass grafts. Median (range) duration of symptoms before the start of thrombolysis was 3.5 (1-14) days in native arteries and 3 (1-9) days in bypass grafts. All patients were treated with a continuous dosage of urokinase (100,000 IU/h). Amputation-free survival was estimated by conduit type using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate analyses were performed using a Cox proportional hazards model. Complete (>95%) lysis was achieved in 69% of native arteries and bypass grafts (P = 1.00). Major hemorrhagic complications occurred in 12% (4% hemorrhagic strokes, of which 2% were fatal) of native arteries and in 7% (0% hemorrhagic stroke) of bypass grafts (P = 0.28). The 30-day mortality rate was 6% in native arteries and 1% in bypass grafts (P = 0.17), and the 30-day amputation rate was 10% in native arteries and 13% in bypass grafts (P = 0.45). Mean follow-up was 27 ± 19 months. Amputation-free survival at 1 year was 76% for native arteries and 78% for bypass grafts and at 5 years was 65% for native arteries and 51% for bypass grafts (P = 0.32). Multivariate analysis showed 2 negative predictors for amputation-free survival: age >65 years and cerebrovascular disease. Conduit type was not an independent predictor for amputation-free survival (P = 0.78). Despite initial promising results, long-term follow-up of catheter-directed thrombolysis for acute lower extremity occlusions showed a disappointing amputation-free survival. In multivariate analysis, no significant differences in amputation-free survival between native arteries and prosthetic bypass grafts were determined.


Consistency evaluation of Liferiver, Yaneng, Darui, and the Cobas 4800 test for high-risk human papillomavirus screening.
In recent years, several high-risk human papillomavirus (HR-HPV) tests have been developed. The assay capabilities need to be systematically reviewed. Here, we compared the clinical sample performance of three novel HR-HPV assays (Liferiver, Yaneng, and Darui) based on different platforms with the widely adopted cobas4800 test. A total of 346 cervical swabs from women who were screened for cervical cancer were analyzed for the presence of 14 HR-HPV genotypes. The distinction between the four assays was investigated by the genotyping and direct sequencing. The positive rates of the four assays ranged from 61.56% to 64.16%. The overall concordance was 88.15%. The Yaneng assays displayed the best sensitivity (100%) and specificity (98.43%). The sensitivity (98.17%) and specificity (98.43%) of the Darui assay were superior to those of the cobas4800 test (97.72% and 93.70%, respectively). The Liferiver assay displayed comparable sensitivity with the cobas4800 test (95.89% and 97.72%, respectively). The specificity of the cobas4800 was lower than that of the Liferiver assay (93.70% vs. 97.64%). The three novel HR-HPV assays displayed good agreement with the cobas4800 test. The analytical performance of all four fulfilled the requirements of sensitivity and specificity for HR-HPV detection.


Integrative analysis of hexaploid wheat roots identifies signature components during iron starvation.
Iron (Fe) is an essential micronutrient for all organisms. In crop plants, Fe deficiency can decrease crop yield significantly; however, our current understanding of how major crops respond to Fe deficiency remains limited. Herein, the effect of Fe deprivation at both the transcriptomic and metabolic level in hexaploid wheat was investigated. Genome-wide gene expression reprogramming was observed in wheat roots subjected to Fe starvation, with a total of 5854 genes differentially expressed. Homoeologue and subgenome-specific analysis unveiled the induction-biased contribution from the A and B genomes. In general, the predominance of genes coding for nicotianamine synthase, yellow stripe-like transporters, metal transporters, ABC transporters, and zinc-induced facilitator-like protein was noted. Expression of genes related to the Strategy II mode of Fe uptake was also predominant. Our transcriptomic data were in agreement with the GC-MS analysis that showed the enhanced accumulation of various metabolites such as fumarate, malonate, succinate, and xylofuranose, which could be contributing to Fe mobilization. Interestingly, Fe starvation leads to a significant temporal increase of glutathione S-transferase at both the transcriptional level and enzymatic activity level, which indicates the involvement of glutathione in response to Fe stress in wheat roots. Taken together, our result provides new insight into the wheat response to Fe starvation at the molecular level and lays the foundation to design new strategies for the improvement of Fe nutrition in crops.


Coupling frontal elution paper chromatography with desorption corona beam ionization mass spectrometry for rapid analysis of chlorphenamine in herbal medicines and dietary supplements.
We developed a convenient method by coupling frontal elution paper chromatography with desorption corona beam ionization mass spectrometry (DCBI-MS) for rapid determination of chlorphenamine added in herbal medicines or dietary supplements. In this method, the ethanol extract of the herbal products was spotted directly onto an isosceles triangular filter paper sheet, and then the paper sheet was developed under strong elution condition with the sample zone migrating at the solvent front. The analyte was finally condensed at the V-shaped tip which could then be placed under the visible plasma beam of DCBI for ionization. The overall procedure took less than 5 min. The frontal elution paper chromatography on a triangular plate used in this work improved the signal intensity of chlorphenamine by 30-fold due to the analyte condensing at the tip and the reduction of the background suppression. Furthermore, the paper sheet also functioned as a filter in the analysis of solid or powder samples, which can increase the analytical throughput by omitting the step of centrifugation. The proposed method in current study was successfully applied in the determination of chlorphenamine in herbal medicines. Chlorphenamine was detected in four of the twelve types of herbal medicines examined in this study. The limit of detection was 200 ng/mL (2.0 ng absolute) in full-scan positive-ion mode and the linear range was from 5.0 μg/mL to 50 μg/mL with satisfactory linear coefficient (R(2) (the square of the correlation coefficient)=0.895). Good reproducibility was achieved with relative standard deviations (RSDs) less than 15.0% and the recoveries of chlorphenamine ranged from 84.3 to 90.6%.


The declining trend of HIV-Infection among pregnant women in Cameroon infers an epidemic decline in the general population.
HIV remains a generalised epidemic in Cameroon, with regular sentinel surveillance surveys (SSS) conducted among pregnant women to monitor the epidemiological dynamics, and for strategic policy making. Our main objective was to actualise data on HIV epidemiology, and compare the trends overtime among pregnant women versus data from the general population in Cameroon. Sentinel surveillance was conducted in 2016 among pregnant women in the 10 regions (60 sites) of Cameroon, targeting 7,000 first antenatal care (ANC-1) attendees (4,000 in urban; 3,000 in rural). HIV testing was done following the serial national algorithm at the National Public Health Laboratory. Results of 2016 were compared with 2009 and 2012 dataset, alongside reports from the general population; with p < 0.05 considered statistical significant. A total of 6,859 ANC-1 (97.99% sampling) were enrolled in 2016, with 99.19% (6,513/6,566) acceptability for HIV testing; similar to performances in 2009 and 2012 (>99%). National prevalence of HIV was 5.70% (389/6,819), similar between urban (5.58%) and rural (5.87%) settings. HIV prevalence among pregnant women declined significantly from 2009 (7.6%), 2012 (7.8%) to 2016 (5.7%), p < 0.0001; with a similar declining trend in the general population: from 2004 (5.5%), 2011 (4.3%) to 2017 (3.4%), p < 0.0001. Difference between SSS and the population-based survey was non-significant (r = 0.6; p = 0.285). Following geographical settings, HIV prevalence was higher in urban vs. rural settings from 2009-2012 (p < 0.0001), followed by similar rates in 2016. Early-age infection (15-24 years) decreased from 6.7% in 2009 to 3.4% in 2016, with remarkable declines in new infections within the age ranges 15-19 years (5.1%-1.57%) and 20-24 years (7.8%-4.39%). With high acceptability in HIV testing, the prevalence of HIV-infection through SSS indicates a declining but generalised epidemic among pregnant women in Cameroon. Of note, as the declining prevalence among pregnant women also reflects an epidemic reduction in the general population, SSS represents an efficient strategy to understand the dynamics of HIV epidemics in the general Cameroonian population, pending validation by periodic population surveys.


Effect of doxapram on control of breathing in cats.
The effects of doxapram infusion (0.25 mg.kg-1. min-1) were studied in cats anaesthetized with pentobarbitone (35 mg . kg-1 intraperitoneally). Cats were studied breathing 50 per cent oxygen and the responses to two concentrations of inspired carbon dioxide were measured. Doxapram infusion increased pulmonary ventilation by increasing both tidal volume and respiratory frequency, and also caused increases in the volume inspired in the first 0.5 second after the onset of an inspiration (V0.5) and the pressure generated in the airway 0.5 second after the onset of an inspiration when the airway had been occluded (P degrees 0.5). V 0.5, P degrees 0.5 and the mean inspiratory flow rate (VT/VI) were essentially equivalent indices of inspiratory drive. Doxapram infusion did not alter the effective impedance of the respiratory system (P degrees 0.5/V 0.5). Doxapram infusion increased the ventilatory response to carbon dioxide. The slope of the ventilatory response to carbon dioxide was increased and the response line was shifted to the left. We conclude that the increase in pulmonary ventilation caused by doxapram infusion is due almost entirely to increased inspiratory neuromuscular drive (P degrees 0.5).


Identification of chlamydosporol, a mycotoxin isolated from a culture of fusarium tricinctum.
Fusarium tricinctum strain (KF 260) isolated from wheat in Poland, produced on maize cultures a compound (C11H14O5, MW226) toxic toArtemia salina. The compound, identified by various spectroscopical tecniques as 5-hydroxy-4-methoxy-6,8a-dimethyl-6, 7-dihydro-2H, 8aH-pyrano/2, 3-b/pyran-2-one, was identical to chlamydosporol, a mycotoxin recentlydiscovered in cultures ofF._ chlamydosporum isolated from rice. The compound showed inhibitory effect on human lymphocyte proliferation at concentration of 25 μg/mL. LD50 onA. salina was 56 μg/mL.


Cathepsin K induces platelet dysfunction and affects cell signaling in breast cancer - molecularly distinct behavior of cathepsin K in breast cancer.
Breast cancer comprises clinically and molecularly distinct tumor subgroups that differ in cell histology and biology and show divergent clinical phenotypes that impede phase III trials, such as those utilizing cathepsin K inhibitors. Here we correlate the epithelial-mesenchymal-like transition breast cancer cells and cathepsin K secretion with activation and aggregation of platelets. Cathepsin K is up-regulated in cancer cells that proteolyze extracellular matrix and contributes to invasiveness. Although proteolytically activated receptors (PARs) are activated by proteases, the direct interaction of cysteine cathepsins with PARs is poorly understood. In human platelets, PAR-1 and -4 are highly expressed, but PAR-3 shows low expression and unclear functions. Platelet aggregation was monitored by measuring changes in turbidity. Platelets were immunoblotted with anti-phospho and total p38, Src-Tyr-416, FAK-Tyr-397, and TGFβ monoclonal antibody. Activation was measured in a flow cytometer and calcium mobilization in a confocal microscope. Mammary epithelial cells were prepared from the primary breast cancer samples of 15 women with Luminal-B subtype to produce primary cells. We demonstrate that platelets are aggregated by cathepsin K in a dose-dependent manner, but not by other cysteine cathepsins. PARs-3 and -4 were confirmed as the cathepsin K target by immunodetection and specific antagonists using a fibroblast cell line derived from PARs deficient mice. Moreover, through co-culture experiments, we show that platelets activated by cathepsin K mediated the up-regulation of SHH, PTHrP, OPN, and TGFβ in epithelial-mesenchymal-like cells from patients with Luminal B breast cancer. Cathepsin K induces platelet dysfunction and affects signaling in breast cancer cells.


Control and isotopic quantification of affinity of antithrombin III for heparin-like surfaces.
Heparin-like materials, characterized by a defined superficial density of functional groups which activate antithrombin III (AT III), when in contact with blood specifically inhibit thrombin as soon as it appears. This paper describes an isotopic method to estimate this density and to visualize the distribution of the affinity sites concerned, both directly with AT III labelled with 125Iodine and indirectly with an anti AT III monoclonal antibody labelled with 111Indium.


[Sensitivity of Plasmodium falciparum to different antimalarials. A study in 1988 in a village in the Hauts-Plateaux of Madagascar].
Since a few years, malaria has reappeared in the Central Highland Plateaux of Madagascar. From 1983 to 1987, Plasmodium falciparum resistance to chloroquine remained stable, with a low frequency of R2 therapeutic failures. In 1988, a study was conducted in the village of Manarintsoa, 15 km from Tananarive. Ninety-one WHO in vivo standard tests were performed. In vitro efficacy of amodiaquine and quinine was also studied. In vitro, the efficacy of chloroquine, quinine, and mefloquine was measured against 104, 64, and 23 P. falciparum isolates, respectively, by an isotopic semi-microtest.


Sodium-dependent and sodium-independent nicotine-evoked catecholamine release from cat adrenals.
Cat adrenal glands were stimulated with nicotine under Na-free conditions; subsequently, Na was gradually introduced as a continuously increasing gradient from 0 to 134 mM. With this experimental approach two catecholamine secretory peak responses were obtained: one was Na-independent and the second was dependent of this cation. This second response was greater in magnitude than the first and selectively blocked by (+)PN200-110, a potent dihydropiridine Ca channel blocker. The results suggest that Na, although not essential to evoke some degree of secretion, plays, however, a prominent role in amplifying the nicotine-secretory response by causing cell depolarization and opening of voltage-dependent Ca channels.


Empathize with the well patient.
The role of empathy in Doctor-Patient interactions with those with MS is explored through a candid account from both sides of the relationship. As "well patients" with MS become more common, the practice of humanistic medicine and intentional displays of empathy become essential for positive interactions.


Low energy harvesting of hydrophobic microalgae (Tribonema sp.) by electro-flotation without coagulation.
Microalgae have great potential for biofuel production and wastewater treatment, but the high cost of harvesting hinders their practical application. In this study, economical harvesting of hydrophobic microalgae by electro-flotation without coagulation was assessed. The harvesting performance of this method for selected species of freshwater microalgae with different degrees of hydrophobicity (Tribonema sp., highly hydrophobic; Scenedesmus sp., moderately hydrophobic; and Pandorina sp., hydrophilic) were compared. It was found that microalgal hydrophobicity played a critical role in electro-flotation. Under the same condition (current 0.3 A, velocity gradient 200 s-1, biomass concentration 1 g/L), Tribonema sp. could be effectively harvested (96.2 ± 0.4%) after 20 min of electro-flotation, while the harvesting efficiency decreased significantly with Scenedesmus sp. (70.1 ± 5.2%, 20 min) and Pandorina sp. (<10%, 1 h). The influences of current, electrolysis time, mixing intensity (velocity gradient) and biomass concentration on Tribonema sp. (hydrophobic) harvesting were further investigated. Increasing the current within a certain range (0.1 A-0.4 A) was beneficial to harvesting, while it's further increase decreased floating velocity, which was similar to the effect of the velocity gradient. Under the optimal condition, the harvesting efficiency of Tribonema sp. was 96.3% and the energy consumption (0.19 kWh/kg biomass) was much lower than other harvesting techniques, indicating that electro-flotation is a time-saving and economical approach for hydrophobic microalgae harvesting.


Studies on accuracy of trichothecene multitoxin analysis using stable isotope dilution assays.
Critical parameters in mycotoxin analysis were examined by using stable isotope-labelled tricho-thecenes. Sample weight was downsized to 1 g without loosing precision when sufficiently homogenized samples were taken for analysis. Complete extraction of trichothecenes could be achieved with a solvent mixture of acetonitrile+water (84+16; v+v) even without the use of stable isotope labelled standards. However, in particular for the analysis of deoxynivalenol the absolute amount of water in the solvent volume used for extraction appeared critical. Depending on the matrix a low water amount resulted in too low quantitative values when no stable isotope-labelled standards are applied to correct for incomplete extraction. In this case the used extraction volume had to be at least 10 ml for 1 g sample when acetonitrile + water (84+16; v+v) was used as extraction solvent.Losses during sample preparation using two different clean-up columns were not observed. On the contrary, matrix suppression in the ESI-interface of the LC-MS equipment was found to be a serious problem. Depending on the matrix, the latter effect resulted in considerably lower values for trichothecenes when no stable isotope-labelled standards were used to counterbalance this suppression.


Periodate-oxidized adenosine inhibits the formation of dimethylselenide and trimethylselenonium ion in mice treated with selenite.
The metabolic detoxification of selenite and many other selenium compounds involves a series of S-adenosylmethionine-dependent methylations yielding dimethylselenide (DMSe), which is exhaled, and trimethylselenonium ion (TMSe), which is excreted in the urine. This paper shows that periodate-oxidized adenosine (Adox) inhibits these methylation reactions in vivo and increases the toxicity of selenite. When Adox was injected in mice at 100 mumol/kg 30 min before injection of [75Se]selenite at 0.4 mg Se/kg the appearances of [75Se]DMSe in the breath and [75Se]TMSe in the liver were completely inhibited for 90 min. This was mediated by accumulation of S-adenosylhomocysteine, the methyltransferase inhibitor, in the livers of Adox-treated mice due to inhibition of its hydrolase enzyme. During 24 h, Adox-treated mice excreted no detectable urinary [75Se]TMSe and exhaled only 20% as much [75Se]DMSe as controls. The urine of Adox-treated mice also contained S-adenosylhomocysteine at a level (ca. 4 mM), 200 times that of untreated mice, which provided a convenient index of methylation potential in the intact animal. When three groups of three mice each were injected with 100 mumol Adox/kg, selenite at 4 mg Se/kg, or a combination of the two, the mice receiving the combination were dead within 2 days, while the mice in the other two groups all survived at least 4 days. These results verify the enzymatic nature of selenium methylation in vivo, support its importance in detoxification, and indicate the value of Adox in further studies of selenium metabolism.


Detection of mcr-1-harbouring Escherichia coli by quantum dot labelling of synthetic small peptides mimicking lipopolysaccharide receptors.
Overuse of antibiotics and the emergence of multidrug-resistant bacteria has made colistin the last line of defence against complex infections. In previous studies, MCR-1-mediated colistin resistance was mainly detected through PCR or antimicrobial susceptibility testing. However, intuitive detection methods for phenotype are rarely reported. In this study, two small peptide antibodies were constructed for immunofluorescence detection of mcr-1-harbouring Escherichia coli: one was a small peptide labelled with a quantum dot antibody; and the other was a small peptide labelled with a fluorescein isothiocyanate (FITC) antibody. Whether using FITC or quantum dots, colistin-resistant bacteria in the sample could be qualitatively detected. The assembled antibodies achieved the desired goals in terms of sensitivity, specificity, precision and repeatability. The non-specific problem of sandwich antigen recognition of lipid A binding to small peptides in modified lipopolysaccharide (LPS) was resolved, and this relatively developed immunofluorescence technique standardised the detection process. Together, in addition to PCR, both fluorescent antibodies can be used for immunofluorescent detection of mcr-1-harbouring E. coli.


Growth-related changes in the ultrastructure of the quadriceps tendon.
The purpose of this study was to investigate the effect of growth on the ultrastructural characteristics of the quadriceps tendon (QT). Eighteen included patients were classified into three groups based on age and epiphyseal plate condition: the 'immature group' consisted of patients with open epiphyseal plates (11.5 ± 1.6 years old; mean ± standard deviation), the 'young group' consisted of patients aged <20 years with closed epiphyseal plates (15.8 ± 1.0 years), and the 'adult group' consisted of all patients aged >20 years (29.8 ± 11.3 years) irrespective of epiphyseal plate condition. Tendon tissue samples were used for ultrastructural analysis by transmission electron microscopy. Minimum collagen fibril diameters were measured from the cross sections of collagen fibril images using Image J software. The average number of collagen fibers per sample was 797 ± 109, and the average collagen fibril diameter of each sample was compared using one-way analysis of variance. The mean collagen fibril diameter was 89.7 ± 14.4 nm in the immature group, 94.8 ± 16.4 nm in the young group, and 107.2 ± 12.1 nm in the adult group, with significant differences between the immature and adult groups, and between the young and adult groups (P = 0.001 and P = 0.021, respectively); however, no significant differences were observed between the immature and young adult groups (P = 0.49). The collagen fibril diameter of the QT was found to have increased with growth. The study provided insights into graft selection.


An inter-laboratory comparison of low-level measurements in ground-level aerosol monitoring.
After the nuclear reactor accident of Chernobyl, the "Integrated Measurement and Information System (IMIS) for Monitoring the Environmental Radioactivity and Detecting Emissions from Nuclear Plants was implemented in Germany. IMIS is a nationwide comprehensive measuring system which permanently monitors the radioactivity in all important environment media in the whole federal territory. At approximately 40 sites, the activity concentration of radioactive substances is measured in air and precipitations. At least 14 of them are responsible for trace monitoring of radionuclides in the air. The legal bases of IMIS prescribe regular inter-laboratory comparison analyses in cooperation with the Physikalisch-Technische Bundesanstalt (PTB), with the use of reference materials prepared by the Federal Coordinating Laboratories. In order to fulfil this requirement in the field of trace survey measurements in ground-level air, the Federal Office for Radiation Protection ("Bundesamt für Strahlenschutz", BfS) and the PTB have conducted a comparison with real, dust-loaded reference filters in 2005. The comparison was organized within the framework of a cooperation of trace survey stations from Austria, Germany and Switzerland. The paper describes the preparation of the real, dust-loaded reference filters, the procedure for spiking the filters with the activity standard solution containing (22)Na, (88)Y, (89)Sr, (90)Sr, (125)Sb, (133)Ba, (134)Cs, and (241)Am. Some results are discussed and conclusions are given.


The regulation of membrane-bound and secreted immunoglobulins in the human lymphoid cell line LICR-LON and human hybridomas.
The synthesis of membrane-bound and secreted immunoglobulin was investigated in the human line LICR-LON-HMy2, a cell line often used for the derivation of human hybridomas. PAGE-SDS analysis of immunoprecipitates obtained from 35S-methionine labelled cell lysates shows that LICR-LON synthesize a hitherto undetected membrane form of IgG (with a heavy chain of mol. wt 62,000) in addition to the secretor form of IgG already described (55,000 heavy chain). Tunicamycin treatment, pulse-chase experiments and Western blot analysis showed that both chains are synthesized as independent proteins. Hybridomas obtained after fusion of LICR-LON and human peripheral blood lymphocytes retained the ability of the parental cell line to synthesize gamma m and gamma s. Some of these hybrids synthesize and secrete IgM which presumably originates from the parental B-lymphocytes. Precipitation and PAGE-SDS analysis of membrane proteins after iodination of intact cells revealed only one heavy chain band, corresponding in size to that of the gamma m. No indication of the synthesis of the membrane form of IgM was found in the hybrids. These data show that the parental (lymphoid) phenotype (m and s-IgG) is codominant with the more differentiated phenotype (s-IgM) of the fusion partner cell (plasma cell). These observations are compatible with a class-specific m-s regulation operating on a different chromatin structure at the expressed Ig loci of each parental chromosome.


Uptake and intracellular activity of moxifloxacin in human neutrophils and tissue-cultured epithelial cells.
The penetration by moxifloxacin of human neutrophils (polymorphonuclear leukocytes [PMN]) and tissue-cultured epithelial cells (McCoy cells) was evaluated by a fluorometric assay. At extracellular concentrations of 5 mg/liter, the cellular-to-extracellular concentration ratios (C/E) of moxifloxacin in PMN and McCoy cells were 10.9 +/- 1.0 and 8.7 +/- 1.0, respectively (20 min; 37 degrees C). The uptake of moxifloxacin by PMN was rapid, reversible, nonsaturable (at extracellular concentrations ranging from 1 to 50 microg/ml), and not affected by cell viability. The uptake of moxifloxacin was affected by external pH and the environmental temperature. The incubation of PMN in the presence of sodium fluoride, sodium cyanide, and carbonyl cyanide m-chlorophenylhydrazone significantly decreased the C/E of this agent. Neither PMN stimulation nor phagocytosis of opsonized Staphylococcus aureus significantly affected the uptake of moxifloxacin by human PMN. This agent, at concentrations of 0.5, 1, and 5 mg/liter, induced a significant reduction in the survival of intracellular S. aureus in human PMN. In summary, moxifloxacin reaches much higher intracellular concentrations within phagocytic and nonphagocytic cells than extracellular ones, remaining active inside the neutrophils.


[Therapy of genital herpes with interferon].
78 women suffering from herpes genitalis have been treated by interferon during two weeks symptomatically. 34 women have been cured. In 30 women an improvement could be observed.


Gene expression profiling of monocytes in recent-onset schizophrenia.
Immune-related mechanisms have been suggested to be involved in schizophrenia. Various studies have shown changes in monocytes isolated from the blood of schizophrenia patients, including changes in monocyte numbers, as well as altered protein and transcript levels of important markers. However, validation of these findings and understanding how these results are related to immune-related changes in the brain and schizophrenia genetic risk factors, is limited. The goal of this study was to better understand changes observed in monocytes of patients with early-onset schizophrenia. Using RNA sequencing, we analyzed gene expression profiles of monocytes isolated from twenty patients with early-onset schizophrenia and seventeen healthy controls. We validated expression changes of 7 out of 29 genes that were differentially expressed in previous studies including TNFAIP3, DUSP2, and IL6. At a transcriptome-wide level, we found 99 differentially expressed genes. Effect sizes of differentially expressed genes were moderately correlated with differential expression in brain tissue (Pearson's r = 0.49). Upregulated genes were enriched for genes in NF-κB and LPS signaling pathways. Downregulated genes were enriched for glucocorticoid response pathways. These pathways have been implicated in schizophrenia before and play a role in regulating the activation of myeloid cells. Interestingly, they are also involved in several non-inflammatory processes in the central nervous system, such as neurogenesis and neurotransmission. Future studies are needed to better understand how dysregulation of the NF-κB and glucocorticoid pathways affects inflammatory and non-inflammatory processes in schizophrenia. The fact that dysregulation of these pathways is also seen in brain tissue, provides potential possibilities for biomarker development.