First report of in vitro resistance of Psoroptes ovis to ivermectin in Argentina.
Sheep scab, or psoroptic mange, a disease caused by the mite Psoroptes ovis, is commonly treated with ivermectin (IVM) and other macrocyclic lactones. In Argentina, in vivo trials have shown a decrease in IVM effectiveness to treat both sheep and bovine scab. In this work, we used an in vitro technique to establish the efficacy of IVM and two other macrocyclic lactones, doramectin (DRM) and moxidectin (MXD), against P. ovis in sheep. Mites were exposed to plates with culture medium and either ethanol or each of the acaricides, and mite mortality at a diagnostic concentration of IVM was assessed. Total survival in one of the strains studied demonstrated the presence of resistance, associated with control failures previously described by the authors. These resistant mites also presented larger LC50 values for both DRM and MXD than expected. Since, in in vivo trials, we had also previously observed a decrease in DRM effectiveness, cross-resistance may exist between DRM and IVM. We propose the use of in vitro tests to evaluate the efficacy of acaricides, considering their practicality, low cost and proven usefulness in detecting resistance in cases of low effectiveness against sheep scab.


Coordination Polymer to Atomically Thin, Holey, Metal-Oxide Nanosheets for Tuning Band Alignment.
Holey 2D metal oxides have shown great promise as functional materials for energy storage and catalysts. Despite impressive performance, their processing is challenged by the requirement of templates plus capping agents or high temperatures; these materials also exhibit excessive thicknesses and low yields. The present work reports a metal-based coordination polymer (MCP) strategy to synthesize polycrystalline, holey, metal oxide (MO) nanosheets with thicknesses as low as two-unit cells. The process involves rapid exfoliation of bulk-layered, MCPs (Ce-, Ti-, Zr-based) into atomically thin MCPs at room temperature, followed by transformation into holey 2D MOs upon the removal of organic linkers in aqueous solution. Further, this work represents an extra step for decorating the holey nanosheets using precursors of transition metals to engineer their band alignments, establishing a route to optimize their photocatalysis. The work introduces a simple, high-yield, room-temperature, and template-free approach to synthesize ultrathin holey nanosheets with high-level functionalities.


[Synthesis of the capsular polysaccharide of Streptococcus pneumoniae type 14].
Synthesis of the regular branched polysaccharide [-6(Gal beta 1-4)GlcNAc beta 1-3Gal beta 1-4Glc beta 1-]n structurally corresponding to capsular polysaccharide of Streptococcus pneumoniae type 14 involves blockwise synthesis of a tritylated 1,2-O-(1-cyano)ethylidene tetrasaccharide derivative from lactosamine and lactose precursors followed by stereospecific polycondensation of the tetrasaccharide monomer.


Factors in the diagnosis and treatment of chronic pain.
Symptoms are the verbal and nonverbal communicative expressions of experience. At any one time, the symptom is dependent on structural changes, genetic variations, metabolic abnormalities, immunopathic and other disorders, and the totality of social, economic, and situational experience. Complaints of pain may vary with time depending on the interaction of these features in a manner not directly related to the intensity of a noxious stimulus.


HIV-1 inhibits haematopoiesis via microRNA secreted by virus-infected CD4+ T cells.
HIV-1-infected patients develop haematological disorders such as cytopenias. One possible explanation is the inhibition of haematopoiesis at the level of differentiation of CD34+ haematopoietic progenitor stem cells. Based on our previous studies, we hypothesised that there may be viral encoded, or host cellular factors which participate in the process of inhibition of haematopoiesis. Virus-depleted media from infected CD4+ T cells was prepared by filtration and added to CD34+ cell differentiation semisolid medium. We have also used the virus-depleted media to isolate host/viral factors including miRNA. Isolated miRNAs were screened for their haematopoietic inhibitory function using the miRNA mining approach. Addition of virus-depleted media caused a 40% inhibition of differentiation of CD34+ cells into myeloid and erythroid colony formation. Real-time RT-PCR showed miR-15a and miR-24 from both pIndie-C1 and pNL4.3 HIV-1-infected cells showed a significant differential expression when compared to control media. In this study, we have identified two miRNAs, miR-15a and miR-24 secreted from purified HIV-1-infected CD4+ T cells that inhibited CD34+ haematopoietic progenitor stem cell differentiation into myeloid and erythroid colonies in vitro.


A case of rectal carcinoma concomitant with Pagetoid lesion in the perianal region--histopathological and electron microscopic observations--.
A case of extramammary Paget's disease of the perianal area adjacent to a mucinous adenocarcinoma of the rectum is presented. The histopathological examination of the case revealed that within the epidermis adjacent to the invading rectal cancer nest, the formation of glandular structures can be observed occasionally, around which so-called Paget's cells are noted to be scattered and further many points of similarity between cancer cell and Paget's cell are proved by electron microscope. Perianal skin lesion looking like Paget's disease is proved to be due to intraepidermal spread of the rectal carcinoma. Referring to the literature, this is the first report to our knowledge, to elucidate the histogenesis of perianal extramammary Paget's disease associated with a rectal carcinoma using the electron microscopy.


Smoking habits and spontaneous abortion.
Smoking habits have been compared in three samples of pregnancies: (1) spontaneous abortions (n = 610); (2) induced abortions (n = 800); and (3) deliveries (n = 1337). The variables studied were, besides smoking habits, day of LMP, outcome of earlier pregnancies, maternal age, and, for the delivery sample, also diagnoses of mother and child, gestational length, sex, and birthweight. A statistical analysis of the association between smoking and the risk of having a spontaneous abortion was made. The comparisons were made with all types of intra-uterine pregnancies but spontaneous abortions, e.g., deliveries and induced abortions. The effects and consequences of that are discussed. The smoking rates according to pregnancy outcome differ among the samples. In the induced abortion sample 58% smoked compared with 50% in the spontaneous abortion sample and 44% in the delivery sample. The well-known effect of smoking on gestational length and birthweight was shown. No significant effect of smoking on the miscarriage risk was seen. The only trend was the opposite. Possible explanations for this are discussed.


Role of ADMA/DDAH-1 and iNOS/eNOS signaling in the gastroprotective effect of tadalafil against indomethacin-induced gastric injury.
Non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastric ulcers represent a significant clinical concern and adversely affect the quality of life. Inducible nitric oxide synthase/endothelial nitric oxide synthase (iNOS/eNOS) and asymmetric dimethylarginine/ dimethylarginine dimethylaminohydrolase-1 (ADMA/DDAH-1) signaling are key players in gastric ulcer pathogenesis. This work was planned to explore the role of iNOS/eNOS and ADMA/DDAH-1 signaling in rats with indomethacin-induced gastric ulcer, as potential pathways for the gastro-protective effect of tadalafil. Split into 5 separate groups, rats were assigned to control, tadalafil (10 mg/kg, p.o), indomethacin (single oral dose of 60 mg/kg), indomethacin + pantoprazole (40 mg/kg, p.o), and indomethacin + tadalafil (10 mg/kg, p.o). The results indicated that pretreatment with tadalafil significantly reduced ulcer index (UI), increased preventive index (PI), and counteracted indomethacin-induced histopathological aberrations. Tadalafil significantly reduced the gastric content of NO while it significantly elevated that of GSH and enhanced SOD activity. It significantly reduced the gastric expression of TNF-α and ADMA while it significantly elevated that of COX-2, PGE-2, and DDAH-1. Western blot analysis revealed that pretreatment with tadalafil significantly reduced iNOS protein expression while it significantly elevated that of eNOS. Collectively, these data suggest that tadalafil exerts potential protective effect against indomethacin-induced ulcer through suppression of inflammation, attenuation of oxidative stress, and boosting of antioxidants. Moreover, tadalafil protective effects are mediated via upregulation of PGE-2 with modulating the signaling pathways of ADMA/DDAH-1, and iNOS/eNOS. As a result, the current evidence corroborates the use of tadalafil in controlling gastric ulcers and preventing NSAID gastric side effects.


Long-term treatment of obese Zucker rats with LY255582 and other appetite suppressants.
LY255582, administered subcutaneously, decreased food intake and body weight gain of fed obese Zucker rats during the entire 30-day period of treatment. No tolerance to these biologic effects of LY255582 could be demonstrated. d-Amphetamine and naltrexone, administered subcutaneously, and d,l-fenfluramine and salbutamol, administered orally, decreased food intake for no more than 6 to 12 days, in contrast to the long-lasting effects of LY255582. Salbutamol suppressed the appetite of obese rats for 3-4 days only. After an additional 12 days of treatment, weight gain decreased significantly accompanied by no appetite suppression. Thus, there is a difference in the duration of action of the opioid antagonist, LY255582, when compared to amphetamine, fenfluramine, naltrexone, and salbutamol, on food intake and body weight gain of obese rats.


Sex differences in the prognostic value of troponin and D-dimer in COVID-19 illness.
Male sex, elevated troponin levels, and elevated D-dimer levels are associated with more complicated COVID-19 illness and greater mortality; however, while there are known sex differences in the prognostic value of troponin and D-dimer in other disease states, it is unknown whether they exist in the setting of COVID-19. We assessed whether sex modified the relationship between troponin, D-dimer, and severe COVID-19 illness (defined as mechanical ventilation, ICU admission or transfer, discharge to hospice, or death). We conducted a retrospective cohort study of patients hospitalized with COVID-19 at a large, academic health system. We used multivariable regression to assess associations between sex, troponin, D-dimer, and severe COVID-19 illness, adjusting for demographic, clinical, and laboratory covariates. To test whether sex modified the relationship between severe COVID-19 illness and troponin or D-dimer, models with interaction terms were utilized. Among 4,574 patients hospitalized with COVID-19, male sex was associated with higher levels of troponin and greater odds of severe COVID-19 illness, but lower levels of initial D-dimer when compared with female sex. While sex did not modify the relationship between troponin level and severe COVID-19 illness, peak D-dimer level was more strongly associated with severe COVID-19 illness in male patients compared to female patients (males: OR=2.91, 95%CI=2.63-2.34, p<0.001; females: OR=2.31, 95%CI=2.04-2.63, p<0.001; p-interaction=0.005). Sex did not modify the association between troponin level and severe COVID-19 illness, but did modify the association between peak D-dimer and severe COVID-19 illness, suggesting greater prognostic value for D-dimer in males with COVID-19.


Changes in cytoplasmic ATP concentration parallels changes in ATP-regulated K+-channel activity in insulin-secreting cells.
Changes in cytoplasmic ATP concentration were monitored in intact insulin-producing cells and correlated to changes in the activity of ATP-sensitive K+-channels (KATP channels). Luciferase was introduced into HIT M2.2 cells and whole pancreatic islets by transient expression of firefly (Photinus pyralis) luciferase cDNA. In transfected cells, extracellular addition of luciferin increased the luminescence signal to a maximum within 50-120 s. Addition of 1 microM of the mitochondrial uncoupler FCCP decreased the luminescence, an effect partly reversed upon withdrawal of the compound. High concentrations of glucose increased cytoplasmic free ATP concentration. Changes in the luminescence signal were accompanied by changes in activity of the ATP-sensitive K+-channel. Transfection per se did not deteriorate cell function, as verified by experiments showing similar changes in cytoplasmic free Ca2+-concentration, [Ca2+li, in both transfected and non-transfected cells. By measuring the cytoplasmic ATP concentration and KATP channel activity under similar experimental conditions, it was possible to establish, for the first time, a direct relationship between these two parameters. This indeed suggests that the cytoplasmic ATP concentration has a crucial role in the regulation of KATP channel activity under physiological conditions.


An evaluation of EU legislation concerning risk assessment and preventive measures in occupational safety and health.
The European Council Directive 89/391/EC of 12 June 1989 is concerned with the introduction of measures to encourage improvements in the occupational safety and health. For example, it deals with risk assessment and preventive measures. The Finnish legislation enacts the risk assessment and prevention measures in a similar way as the EU Directive 89/391/EC. The aim of this study was to examine: 1) the implementation of risk assessment process as a part of OSH management, and 2) the effectiveness of the OSH legislation concerned with risk assessment. The quantitative method involved an online questionnaire. The respondents were employers (N = 1478), workers (N = 1416) and occupational care (OHC) professionals' units (N = 469). Three quarters of the employer respondents and two thirds of the workers and OHC service providers felt that the EU legislative provisions have promoted the engagement of the management. According to the study, improvement is needed in ensuring the cooperation between employers and workers. The combined variables of Risk Assessment Process revealed positive impacts both on Cooperation and Management Measures and on the Concrete Preventive Measures among the employers and the workers. The combined variables of Use of Documents of Risk Assessments highlighted positive impacts on both the Exploiting of Results of Risk Assessments in Planning and Management and on the Exploiting of Results of Risk Assessment in Cooperation and Technology.


Removal of cardiodepressant antibodies in dilated cardiomyopathy by immunoadsorption.
The objective of this study was to investigate whether immunoadsorption (IA) removes cardiodepressant antibodies from the plasma of patients with dilated cardiomyopathy (DCM), as well as to describe their effects on isolated rat cardiomyocytes. Immunoadsorption induces early hemodynamic improvement in patients with DCM. The mechanisms for this improvement remain to be elucidated. Patients with DCM (n = 11; left ventricular ejection fraction < 30%, cardiac index [CI] < 2.5 l/min per m(2)) were treated with IA on three consecutive days, with one IA session daily, by application of specific antibody columns directed against human immunoglobulin (Ig). Immunoadsorption was also conducted on 500 ml of blood taken from nine healthy donors (control subjects). After passage of plasma, the IA columns were regenerated. Column eluent (CE) was collected and dialyzed (100 kD). Confocal laser scanning microscopy was used to analyze the effects of CE on cell contraction and on Ca(2+)-dependent fluorescence in isolated, field-stimulated adult rat cardiomyocytes loaded with cell-permeable Fluo-3. Immunoprecipitation with different preparations of myocardial protein fractions was used for characterization of cardiotropic antibodies. During IA, the IgG plasma level decreased from 10.7 +/- 0.6 to 2.4 +/- 0.1 g/l (mean +/- SEM), and the CI increased from 2.2 +/- 0.1 to 2.7 +/- 0.2 l/min per m(2) (p < 0.01). The CE obtained from control subjects did not influence Ca(2+) transients or cell shortening of cardiomyocytes. In contrast, in patients with DCM, the CE collected during the first regeneration cycle of the first IA session caused an immediate and dose-related decrease of Ca(2+) transients (dilution 1:5; -22.7 +/- 5.5%; p < 0.01) and cell shortening (dilution 1:5; -29.9 +/- 6.0%, p < 0.01). Early hemodynamic improvement among the patients correlated with the cardiodepressant effect of CE on the isolated cardiomyocytes. Purification of CE by protein A adsorption indicated that the cardiodepressant substances are antibodies. Immunoprecipitation revealed that the eliminated antibodies are capable of binding to various myocardial proteins. Cardiac autoantibodies play a functional role in DCM, and their removal may induce early hemodynamic improvement.


Land consumption monitoring: an innovative method integrating SAR and optical data.
In this paper, the use of synthetic aperture radar (SAR) for the monitoring of land consumption is analyzed. The paper presents an automatic procedure that integrates SAR and optical data, which can be effectively used to generate land consumption maps or update existing maps. The main input of the procedure is a series of SAR amplitude images acquired over a given geographical area and observation period. The main assumption of the procedure is that land consumption is associated with an increase of the SAR amplitude values. Such an increase is detected in the SAR amplitude time series using an automatic Bayesian algorithm. The results based on the SAR amplitude are then filtered using an NDVI map derived from optical imagery. The effectiveness of the proposed procedure is illustrated using SAR data from the Sentinel-1 and TerraSAR-X sensors, and optical data from the Sentinel-2 sensor.


Investigating biological activity spectrum for novel quinoline analogues 2: hydroxyquinolinecarboxamides with photosynthesis-inhibiting activity.
Two series of amides based on quinoline scaffold were designed and synthesized in search of photosynthesis inhibitors. The compounds were tested for their photosynthesis-inhibiting activity against Spinacia oleracea L. and Chlorella vulgaris Beij. The compounds lipophilicity was determined by the RP-HPLC method. Several compounds showed biological activity similar or even higher than that of the standard (DCMU). The structure-activity relationships are discussed.


Enzyme activities in tissues of clinically normal Large White pigs. Variations with age and sex.
The activities of eight enzymes (glutamate dehydrogenase, sorbital dehydrogenase, malate dehydrogenase, lactate dehydrogenase, alpha-hydroxy butyrate dehydrogenase, gamma-glutamyl transpeptidase, alkaline phosphatase and creatine kinase) were determined in tissue homogenates of liver, kidney, spleen, lung, small intestine, cardiac muscle and skeletal muscle, from 15 Large White pigs of three different ages (1.5 weeks, 18--22 weeks and 113 weeks). The results showed that variation in tissue enzyme concentration due to differences in sex is minimal. Variation due to differences in age, however, appears to be of greater importance, particularly when considering young animals. These age differences may affect the interpretation of plasma enzyme changes due to tissue damage, and the use of additional enzyme assays as an aid to interpretation in these cases is advisable.


Scopolamine impairs behavioural function and arginine metabolism in the rat dentate gyrus.
Alzheimer's disease (AD) is a neurodegenerative disorder with progressive memory loss. It has been shown that the cholinergic neurotransmission deficit is one of the neurochemical characteristics of AD, and that L-arginine and its metabolites also play a prominent role in AD pathogenesis. Scopolamine, a non-selective muscarinic receptor antagonist, blocks cholinergic neurotransmission and impairs behavioural function, including learning and memory. This study investigated the effects of scopolamine on animals' behavioural performance and L-arginine metabolism in the hippocampus and prefrontal cortex. Rats were given intraperitoneal injections of scopolamine (0.8 mg/kg) or saline (1 ml/kg) and tested in the Y-maze, open field, water maze and elevated plus maze 30 min post-treatment. After completion of the behavioural testing, the CA1, CA2/3 and dentate gyrus (DG) sub-regions of the hippocampus and the prefrontal cortex were harvested to measure the activity and protein expression of nitric oxide synthase (NOS) and arginase, and the levels of L-arginine, L-citrulline, L-ornithine, agmatine, putrescine, spermidine, spermine, glutamate and GABA. Scopolamine treated rats displayed reduced alternation and exploratory behaviour, increased swimming speed and impaired spatial learning and memory. There were significantly decreased NOS activity, increased arginase activity, and increased L-ornithine and putrescine levels in the DG, but not other regions examined, in the scopolamine treated rats as compared to the controls. These findings suggest that scopolamine impairs behavioural function and alters L-arginine metabolism in the DG sub-region of the hippocampus specifically. The underlying mechanisms of it remain to be explored further.


The effect of diagnostic methodology on the sensitivity of the TRH stimulation test for depression: a literature review.
The authors review over 50 reports comparing test sensitivity of the thyrotropin-releasing hormone (TRH) stimulation test using either DSM-III or Research Diagnostic Criteria (RDC) criteria for depression. Ten reports with a total of 410 patients and 458 test results were analyzed that met specific criteria for diagnosis for the TRH test. The sensitivity for depression with the TRH test in the DSM-III reports was 34.8% compared with six RDC reports in which the sensitivity was 51% (chi 2 10.41, p less than 0.001). The authors discuss possible endocrine and psychiatric implications of this finding and encourage researchers to use two methods for diagnosis in future clinical research in order that this type of comparison can be undertaken in the same patients. This will help in future modifications and revisions of the DSM.


Relationship between the degree of abdominal wall movement and the image quality of contrast-enhanced MRI: semi-quantitative study especially focused on the occurrence of transient severe motion artifact.
To reveal the relationship between abdominal movement and artifact, and to reveal if the transient artifact in arterial phase is caused by transient abdominal movement (TAM) in contrast-enhanced (CE) MRI. 325 CE-MRI series (206 with EOB and 119 with EGCM) were included. The abdominal movement was classified into three groups by respiratory bellows waveform (= bellows grade, BG 1-3), and MR image quality (= artifact score, AS) was graded 1-5 for the precontrast, arterial and portal venous phase, respectively. The relationship between the BG and AS was evaluated. The occurrence of transient artifact in arterial phase was compared to the degree of TAM. In the acquisitions with BG3, all images showed AS of > 2, while no images had AS of > 4 in the acquisitions with BG1. Numbers of transient artifact in the arterial phase with no-abdominal movement (NAM), mild-TAM, severe-TAM were 0 of 120, 4 of 27, 7 of 8 in EOB and 0 of 91, 1 of 4, 0 of 0 in EGCM, respectively. Image quality is highly correlated with abdominal movement. Moreover, artifact in arterial phase was not observed in NAM, which indicated abdominal movement is the direct cause of artifact.


Aligned porous materials by directional freezing of solutions in liquid CO2.
We report here a method for generating structures with aligned macropores by templating solidified carbon dioxide. The CO2 template phase can be removed by direct sublimation to yield a dry, solvent-free porous material that may be useful in applications such as tissue engineering and aligned cell growth.


Soluble forms of the cell adhesion molecule L1 produced by insect and baculovirus-transduced mammalian cells enhance Schwann cell motility.
For biotechnological applications, insect cell lines are primarily known as hosts for the baculovirus expression system that is capable to direct synthesis of high levels of recombinant proteins through use of powerful viral promoters. Here, we demonstrate the implementation of two alternative approaches based on the baculovirus system for production of a mammalian recombinant glycoprotein, comprising the extracellular part of the cell adhesion molecule L1, with potential important therapeutic applications in nervous system repair. In the first approach, the extracellular part of L1 bearing a myc tag is produced in permanently transformed insect cell lines and purified by affinity chromatography. In the second approach, recombinant baculoviruses that express L1-Fc chimeric protein, derived from fusion of the extracellular part of L1 with the Fc part of human IgG1, under the control of a mammalian promoter are used to infect mammalian HEK293 and primary Schwann cells. Both the extracellular part of L1 bearing a myc tag accumulating in the supernatants of insect cultures as well as L1-Fc secreted by transduced HEK293 or Schwann cells are capable of increasing the motility of Schwann cells with similar efficiency in a gap bridging bioassay. In addition, baculovirus-transduced Schwann cells show enhanced motility when grafted on organotypic cultures of neonatal brain slices while they retain their ability to myelinate CNS axons. This proof-of-concept that the migratory properties of myelin-forming cells can be modulated by recombinant protein produced in insect culture as well as by means of baculovirus-mediated adhesion molecule expression in mammalian cells may have beneficial applications in the field of CNS therapies.


The evolution of eosinophilic granuloma of bone: a case report.
A case of eosinophilic granuloma in the humerus of a three and a half year old boy is described with serial roentgenographic evidence of the lesion developing over a period of two months prior to the commencement of treatment. After open biopsy and local steroid injection the lesion was observed to heal during the next ten months.


Effects of nutrient amendments on fine root biomass in a primary successional forest in Hawai'i.
We determined the effect of fertilization treatments (control (C), complete nutrient amendment without nitrogen (PT), nitrogen only (N) and a complete nutrient amendment (NPT)) on fine root biomass in a tropical montane forest in Hawai'i. Fertilization significantly decreased root biomass; live fine root mass (<2 mm diameter) for the C, PT, N and NPT treatments were 335, 145, 110 and 105 g·m-2, respectively. Nutrient availability appears to control fine root mass in this primary successional forest.


Aspects of glucose homeostasis in uremia as assessed by the hyperinsulinemic euglycemic clamp technique.
A three-step hyperinsulinemic euglycemic clamp was performed in 14 nondialyzed uremic and ten age-matched healthy subjects. Nine of the uremics were restudied for a mean of 42 days (range, 21 to 88 days) after initiation of dialysis therapy. Insulin was infused at the following three rates: 0.5 mU X kg-1 X min-1, 2.0 mU X kg-1 X min-1, and 4.0 mU X kg-1 X min-1. Each dose was given for 120 minutes. Glucose uptake during the last 30 minutes of each clamp were consistently lower in uremic patients pre-dialysis than in controls (2.3 +/- 0.3 v 6.6 +/- 0.8 mg X kg-1 X min, 7.8 +/- 0.6 v 13.2 +/- 1.1 mg X kg-1 X min-1 and 9.6 +/- 0.7 v 15.5 +/- 1.0 mg X kg-1 X min-1, all P less than 0.001). Serum insulin levels were similar in the two groups, and blood glucose values during steady state were maintained at 79 +/- 2.77 +/- 2, and 77 +/- 2 mg/100 mL in uremic subjects and at 72 +/- 3, 73 +/- 2, and 75 +/- 2 mg/100 mL in healthy subjects. The insulin levels required to elicit half-maximal biological response in uremics (82 +/- 5 microU/mL) were markedly higher than in controls (54 +/- 8 microU/mL, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


Radioimmunoassay of 11-dehydrothromboxane B2 in human plasma and urine.
Because of the discrepancy between the capacity of platelets to synthesize thromboxane B2 ex vivo and the actual synthetic rate in vivo, measurement of thromboxane B2 in plasma is highly influenced by sampling-related artifacts. We have developed and validated a radioimmunoassay for a major enzymatic derivative of thromboxane B2 with an extended plasma half-life, i.e., 11-dehydrothromboxane B2. The binding of the tracer is displaced by as low as 1 pg/ml of the homologous ligand, with a high degree of specificity for the open ring structure as well as for the omega side-chain. This method can detect changes in the plasma concentration and urinary excretion of 11-dehydrothromboxane B2 associated with stimulated short-term increases of thromboxane B2 secretion in the human circulation.


Surgical stabilization of severe rib fractures decreases incidence of retained hemothorax and empyema.
Retained hemothorax (RH) is relatively common after chest trauma and can lead to empyema. We hypothesized that patients who have surgical fixation of rib fractures (SSRF) have less RH and empyema than those who have medical management of rib fractures (MMRF). Admitted rib fracture patients from January 2009 to June 2013 were identified. A 2:1 propensity score model identified MMRF patients who were similar to SSRF. RH, and empyema and readmissions, were recorded. Variables were compared using Fisher exact test and Wilcoxon rank-sum tests. One hundred thirty-seven SSRF and 274 MMRF were analyzed; 31 (7.5%) had RH requiring 35 interventions; 3 (2.2%) SSRF patients had RH compared with 28 (10.2%) MMRF (P = .003). Four (14.3%) MMRF subjects with RH developed empyema versus zero in the SSRF group (P = .008); 6 (19.3%) RH patients required readmission versus 14 (3.7%) in the non-RH group (P = .002). Patients with rib fractures who have SSRF have less RH compared with similar MMRF patients. Although not a singular reason to perform SSRF, this clinical benefit should not be overlooked.


The epidural venogram as a diagnostic procedure in the young athlete with symptoms of lumbar disk disease.
We recommend lumbar epidural venography as a screening procedure before myelography in the young athlete. It can be done on an outpatient basis, has a low complication rate, leaves no residual contrast material, and is more pleasant to the patient than a myelogram.


Quantitative Microbial Risk Assessment for Clostridium perfringens in Natural and Processed Cheeses.
This study evaluated the risk of Clostridium perfringens (C. perfringens) foodborne illness from natural and processed cheeses. Microbial risk assessment in this study was conducted according to four steps: hazard identification, hazard characterization, exposure assessment, and risk characterization. The hazard identification of C. perfringens on cheese was identified through literature, and dose response models were utilized for hazard characterization of the pathogen. For exposure assessment, the prevalence of C. perfringens, storage temperatures, storage time, and annual amounts of cheese consumption were surveyed. Eventually, a simulation model was developed using the collected data and the simulation result was used to estimate the probability of C. perfringens foodborne illness by cheese consumption with @RISK. C. perfringens was determined to be low risk on cheese based on hazard identification, and the exponential model (r = 1.82×10(-11)) was deemed appropriate for hazard characterization. Annual amounts of natural and processed cheese consumption were 12.40±19.43 g and 19.46±14.39 g, respectively. Since the contamination levels of C. perfringens on natural (0.30 Log CFU/g) and processed cheeses (0.45 Log CFU/g) were below the detection limit, the initial contamination levels of natural and processed cheeses were estimated by beta distribution (α 1 = 1, α 2 = 91; α 1 = 1, α 2 = 309)×uniform distribution (a = 0, b = 2; a = 0, b = 2.8) to be -2.35 and -2.73 Log CFU/g, respectively. Moreover, no growth of C. perfringens was observed for exposure assessment to simulated conditions of distribution and storage. These data were used for risk characterization by a simulation model, and the mean values of the probability of C. perfringens foodborne illness by cheese consumption per person per day for natural and processed cheeses were 9.57×10(-14) and 3.58×10(-14), respectively. These results indicate that probability of C. perfringens foodborne illness by consumption cheese is low, and it can be used to establish microbial criteria for C. perfringens on natural and processed cheeses.


Risk Groups of Developing Active Tuberculosis in Liver Transplant Recipients in a Tuberculosis Endemic Area: Risk Stratification by Chest Image and Interferon Gamma Release Assay.
We implemented a stratified risk analysis to predict the development of active tuberculosis (TB) in liver transplantation (LT) recipients based on IGRA and chest images in a TB-endemic area. In this retrospective cohort study, LT recipients who tested for IGRA between May 2008 and December 2017 were included. Chest images compatible with old TB lesions were considered as positive images. LT recipients were divided into six groups: LT recipients with history of treated TB, image (+)/IGRA (+), image (+)/IGRA (-), image (-)/IGRA (+), image (-)/IGRA (-) and LTBI treated. The Cox regression model was used to analyze risk groups. Among the 717 eligible LT recipients included in this study, 21 patients developed active TB. Incidence rates of TB were 2,261, 724, and 119 cases/100,000 person-years in the 1st, 2nd, and ≥ 3rd year after transplantation, respectively. History of treated TB (HR 18.92; 95% CI 4.10-87.25) and image (+)/IGRA (+) (HR 10.86; 95% CI 2.75-42.89) were independent risk factors for developing active TB. IGRA (+) with a negative image was not a risk factor. Our findings suggested that both IGRA and chest images should be considered to identify risk groups for LTBI treatment.


Stress reduction by technology? An experimental study into the effects of brainmachines on burnout and state anxiety.
Stress and burnout are widely acknowledged as major causes of societal and individual problems in the Western world. In order to reduce material and immaterial expenses, increased efforts are made to enhance relaxation and stress reduction. Based on neuropsychological findings, alternative ways have been explored, one of them being the application of so-called brain wave synchronizers, which are said to induce a relaxation response by entraining alpha brain-wave activity (8-13 Hz) through audiovisual stimulation. A double blind, quasi-experiment was conducted among employees at a Dutch addiction care center to investigate the possible effects of two distinct brainmachine programs on burnout and anxiety. Subjects in both conditions showed a significant, immediate decrease in state anxiety as assessed by Spielberger's State-Trait Anxiety Inventory (STAI) and reported a range of subjective effects. However, a long-term effect on burnout, as measured with Maslach's Burnout Inventory (MBI-NL), could not be established. A long-term effect on anxiety (STAI), as investigated by interrupted time-series measurement, could not be established either. These and other findings suggest that the major claims with respect to these machines cannot hold over time, although pleasant short-term effects do occur. Individual differences in baseline responsivity, the stable character of burnout dimensions, or the ill-defined nature of relaxation, or a combination of these, may account for these results.


Subtotal duodenopancreatectomy for pancreatic duct, distal bile duct and periampullary carcinoma: short- and long-term results.
Ninety patients with pancreatic duct, distal bile duct, and ampullary carcinoma underwent pancreatic resection. Following a standard policy of resection based on surgical findings, all the patients who had resection first underwent subtotal extended pancreatectomy (n = 68) and if they were considered not to fulfill the criteria for this operation, total pancreatectomy (n = 22). Thus, 68 of the 90 patients (72%) were managed with subtotal pancreatic resection irrespective whether they had ampullary, pancreatic duct, or distal common bile duct carcinoma. On the basis of our results, subtotal duodenopancreatectomy is regarded as the method of choice for many patients with pancreatic duct, distal bile duct, or ampullary carcinoma.


Spiritual health locus of control and health behaviors in African Americans.
To examine relationships between spiritual health locus of control beliefs and various health behaviors. A cross-sectional survey of a national sample of African Americans assessed spiritual beliefs, fruit and vegetable consumption, physical activity, and alcohol consumption. Active spiritual beliefs were positively associated with fruit consumption and negatively associated with alcohol consumption. Passive spiritual beliefs were associated with lower vegetable and increased alcohol consumption. Among male participants, passive spiritual beliefs were associated with higher alcohol consumption. Findings suggest that dimensions of spiritual health locus of control beliefs have complex and varying relationships with health behaviors.


Measurement of the alpha 2 component of a novel oncodevelopmental antigen by a rapid electroimmunoassay.
A method was required for the quantification of a novel oncodevelopmental antigen which increases in the serum of pregnant women as well as patients with ovarian cancer. The native antigen is composed of two components having alpha 2 and beta electrophoretic mobilities. An assay method, involving electroimmunodiffusion according to Laurell, was developed for the measurement of the alpha 2 component of the antigen. The method is sufficiently sensitive to determine significant differences in the levels of antigen in the serum of non-pregnant and pregnant subjects, and patients with ovarian cancer. In addition to routine quantitation, the technique will also be an indispensable analytical tool in the purification of the protein.


PET/CT in a patient with cardiac paraganglioma.
A 22-year-old female with SDHB-positive who presented with palpitation and hypertension after adrenalectomy was performed 18F-FDG PET/CT to detect the primary ectopic pheochromocytoma (PCC) and rule out metastasis. PET/CT is useful for detecting and localizing the primary ectopic PCC.


Prevalence and features of delirium in older patients admitted to rehabilitation facilities: a multicenter study.
Delirium is thought to be common across various settings of care; however, still little research has been conducted in rehabilitation. We investigated the prevalence of delirium, its features and motor subtypes in older patients admitted to rehabilitation facilities during the three editions of the "Delirium Day project". We conducted a cross-sectional study in which 1237 older patients (age ≥ 65 years old) admitted to 50 Italian rehabilitation wards during the three editions of the "Delirium Day project" (2015 to 2017) were included. Delirium was evaluated through the 4AT and its motor subtype with the Delirium Motor Subtype Scale. Delirium was detected in 226 patients (18%), and the most recurrent motor subtype was mixed (37%), followed by hypoactive (26%), hyperactive (21%) and non-motor one (16%). In a multivariate Poisson regression model with robust variance, factors associated with delirium were: disability in basic (PR 1.48, 95%CI: 1.17-1.9, p value 0.001) and instrumental activities of daily living (PR 1.58, 95%CI: 1.08-2.32, p value 0.018), dementia (PR 2.10, 95%CI: 1.62-2.73, p value < 0.0001), typical antipsychotics (PR 1.47, 95%CI: 1.10-1.95, p value 0.008), antidepressants other than selective serotonin reuptake inhibitors (PR 1.3, 95%CI: 1.02-1.66, p value 0.035), and physical restraints (PR 2.37, 95%CI: 1.68-3.36, p value < 0.0001). This multicenter study reports that 2 out 10 patients admitted to rehabilitations had delirium on the index day. Mixed delirium was the most prevalent subtype. Delirium was associated with unmodifiable (dementia, disability) and modifiable (physical restraints, medications) factors. Identification of these factors should prompt specific interventions aimed to prevent or mitigate delirium.


Pre-hospital exposures to antibiotics among children presenting with fever in northern Uganda: a facility-based cross-sectional study.
The rise in the indiscriminate use of antibiotics has become a major global public health problem and presents the biggest global health challenge in the twenty-first century. In developing countries, caregivers initiate treatment with antibiotics at home before presentation to a health facility. However, there is a paucity of evolving data towards surveillance of this trend in low-income countries. We investigated antibiotic use among febrile children presenting to a tertiary health facility in northern Uganda. We conducted a cross-sectional study in a tertiary health facility in northern Uganda between March and September 2021. Children aged 6-59 months with fever were selected using systematic random sampling. A pre-tested interviewer-administered questionnaire was used the collect clinical data from the caregivers. Data were analyzed using SPSS version 23. Descriptive statistics and multiple logistic regression models were applied. P-value < 0.05 was considered for statistical significance. Eighty-three (39.5%) of the 210 children with fever in this study used antibiotics prior to the hospital visit, 55.4% of which were on a self-medication basis, while 44.6% were empiric prescriptions. The most commonly used antibiotics were amoxicillin 33/83 (39.8%), erythromycin 18 (21.7%), metronidazole 14 (16.9%), ciprofloxacin 13 (15.7%) and ampicillin 6 (7.2%). The main sources of the antibiotics included buying from drug shops 30/83 (36.1%), issuance from clinics (33.7%), remnants at home (12.0%), picking from a neighbour (7.2%) and others (10.8%). The factors associated with antibiotic use among the febrile children were residence (p < 0.001); distance from the nearest health facility (p = 0.005); caregivers' gender (p = 0.043); cough (p = 0.012); diarrhoea (p = 0.007); duration of fever (p = 0.002); perceived convulsion complicating fever (p = 0.026), and caregivers' perception that fever (p = 0.001), cough (p = 0.003), diarrhoea (p < 0.001) and any infection (p < 0.001) are indications for antibiotics. Inappropriate use of antibiotics for childhood febrile illnesses is prevalent in the study setting, facilitated by the ease of access and use of leftover antibiotics. There is a need to address communities' health-seeking behaviour and the health providers' practice alike.


Quantification of brain lipids by FTIR spectroscopy and partial least squares regression.
Brain tissue is characterized by high lipid content. Its content decreases and the lipid composition changes during transformation from normal brain tissue to tumors. Therefore, the analysis of brain lipids might complement the existing diagnostic tools to determine the tumor type and tumor grade. Objective of this work is to extract lipids from gray matter and white matter of porcine brain tissue, record infrared (IR) spectra of these extracts and develop a quantification model for the main lipids based on partial least squares (PLS) regression. IR spectra of the pure lipids cholesterol, cholesterol ester, phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingomyelin, galactocerebroside and sulfatide were used as references. Two lipid mixtures were prepared for training and validation of the quantification model. The composition of lipid extracts that were predicted by the PLS regression of IR spectra was compared with lipid quantification by thin layer chromatography.


Complications of Penumbra Indigo Aspiration Device in Pulmonary Embolism: Insights From MAUDE Database.
The Penumbra Indigo aspiration system (Penumbra Inc., Alameda, CA, USA) is a suction embolectomy device that was cleared by the Food and Drug Administration for use in acute pulmonary embolism (PE). While this device has proven to be safe in clinical trials, real-world data are minimal. The "Manufacturer and User Facility Device Experience" MAUDE database was queried for reports of Penumbra indigo system from January 2020 to August 2021. A total of 2118 reports were found during the study period. After the exclusion of duplicate and incomplete reports as well as reports not related to PE, our final cohort included 67 reports related to Penumbra indigo device failure. The most common failure mode was Lightning unit malfunction (35.8%, n = 24) followed by rotating hemostasis valve malfunction (31.3%, n = 21). Three (4.5%) patients died; two (3%) from fatal pulmonary vessel perforation, and one from fatal right-sided heart failure. There was one case (1.5%) of pericardial effusion, while there were no cases of hemoptysis or blood transfusion. The overall number of reports in the MAUDE registry related to the Penumbra Indigo aspiration system is small (67 reports in 20 months). The most common reported failure mode was Lightning unit malfunction. These data serve to inform operators about potential issues when using the Penumbra Indigo thrombus aspiration system and identify areas on which to focus further device iteration.


Predictors of long-term clinical response to interferon beta therapy in relapsing multiple sclerosis.
The aim of this study was to identify clinical, magnetic resonance imaging (MRI) and biological markers predictive of long-term clinical response to interferon beta (IFN beta) therapy in patients with relapsing-remitting multiple sclerosis (RRMS). Sixty-eight patients treated with IFN beta were followed over a 6-year period. Relapse rate and disability progression were evaluated throughout the study. We considered suboptimal clinical response to be either the presence of sustained disability progression, or more than two relapses. Baseline and 12-month demographic, clinical and MRI findings, as well as the development of neutralizing antibodies (NAbs) against IFN beta during the first year of therapy were analyzed as predictors of long-term clinical outcome. "Black holes" on MRI were the best baseline predictor of disability progression (odds ratio [OR] 6.8; p < 0.001). At 1 year, both male gender (OR 4.9; p = 0.009) and NAbs (OR 7.3; p = 0.003) were independently associated with a high risk of developing subsequent disability. The presence of gadolinium enhancement, both at baseline (OR 4.7; p = 0.005) and on the 1-year MRI scan (OR 7.9; p = 0.002), was the unique variable associated with the number of relapses over the study period. Variables assessable within the first year of treatment significantly influence relapse rate and disability progression in patients with RRMS treated with IFN beta. These findings may help clinicians to make decisions regarding therapy regimen over time, and highlight the need for a prognostic algorithm.


Involvement of AMPA receptors of lateral habenula in the expression and acquisition phases of morphine-induced place preference.
The lateral habenula (LHb), known as the brain structure of the epithalamic, plays the main role in depression and drug addiction. The glutamatergic system influences morphine reward. The effect of activation/inhibition of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors (AMPARs) in the LHb on different phases of morphine-induced conditioned place preference (CPP) remains unknown. In this research, the effect of bilateral intra-LHb microinjection of AMPARs agonist and antagonist on the acquisition and expression phases of CPP in male rats has been investigated. Different doses of NBQX, the antagonist of AMPARs, in combination with the effective dose of morphine, increased the CPP score during the acquisition phase. While AMPA, the agonist of AMPARs, significantly reduced the conditioning scores in the acquisition phase. Pretreatment with NBQX (0.5 and 1 μg/rat) reversed the inhibitory effect of AMPA (1 μg/rat) on the acquisition phase of morphine-induced CPP. The antagonist (1 μg/rat) increased the effect of a high dose of agonist (2 μg/rat) on CPP. On the other hand, NBQX significantly increased CPP scores during the expression phase. AMPA did not significantly affect CPP scores in the expression phase, but significantly reduced locomotor activity in the test phase. These results confirmed the importance of AMPARs in the LHb in morphine reward. Our data also suggest that injection of an AMPARs antagonist into the LHb may alter the AMPA-induced morphine response in a dose-dependent manner.


Evolution of teaching in short-term courses: A systematic review.
Short-term courses are a useful tool for continuous training to update and deepen knowledge in various fields. In this article, we analyse the evolution of the teaching methods used in short-term courses through a systematic review conducted using the PRISMA methodology. The inclusion criteria for selecting articles were those that described the methodological structure of the teaching methods used in designing short-term courses. The exclusion criteria were courses longer than 90 days and unfinished documents. The search was conducted on April 9, 2022, using the SCOPUS database. The list of papers was reviewed and analysed three times by different researchers to ensure that they met the criteria. Articles approved by at least two researchers were selected. The results were systematically analysed based on criteria that allowed us to understand the learning methods used, such as the educational modality, content presentation, teaching methodology for teamwork and individual work, technological resources, and assessment methods. We selected 42 articles, and the results are presented in four parts: the learning experience, teaching methodology, technological resources, and assessment methods. One of the main findings is that short-term courses are primarily designed for experiential learning, and memory-related activities commonly used in traditional training are not typically included in short-term courses.


Functional disability in the rheumatoid hand.
The investigation of sixty-one rheumatoid patients relates their hand function to measured hand deformity. Certain deformities are related to a reduction in function; others are not. The dominant hand, used more frequently, deteriorates more quickly than the non-dominant. The benefit on hand function of synovectomy is limited in duration and should be accompanied by some procedure to defer or correct deformity. Study of the metacarphophalangeal joints by radiography and at operation shows that degeneration starts where the metacarpal head first loses articulation with the base of the phalanx, and spreads out from there across the metacarpal head as deformity increases.


The location of intraparenchymal bleeding determines functional outcome after spontaneous subarachnoid hemorrhage.
Non-traumatic subarachnoid hemorrhage (SAH) is a devastating disease associated with high morbidity and mortality. A higher blood burden and the presence of intraparenchymal extension of the bleeding (intracerebral hemorrhage [ICH]) are well known predictors of poor outcome. Only few studies have addressed the role of hematoma location on patient's functional outcome. The main aims were to compare clinical and radiographic characteristics between SAH patients with and without ICH and to compare different ICH localizations in relation to long-term functional outcome. We prospectively collected data on 280 consecutive SAH patients (aneurysmal and non-aneurysmal) admitted to a tertiary care hospital between 2010 and 2017 and assessed the initial computed tomography scans of the brain acquired after intensive care unit admission. Poor functional outcome was defined as a modified Rankin Scale score >2, 3 months after SAH. We used multivariable logistic linear regression to investigate associations between ICH location and clinical variables as well as functional outcome. Intraparenchymal extension of the hemorrhage was observed in 59/280 patients (21%). The median (interquartile range) ICH volume was 11.3 (4.9-16.2) ml and the location was supratentorial in 55/59 patients (93%). Most parenchymal hemorrhages were located in the frontal (n = 24.41%) and temporal lobes (n = 12.21%), followed by insular ICH (n = 7.12%), corpus callosum (n = 6.10%), parietal (n = 2.3%) and occipital locations (n = 2.3%). Among SAH patients with ICH, those with lesions located in the corpus callosum (n = 6/59) had a significantly higher risk of 3-month poor functional outcome in comparison to all other ICH locations, even after adjusting for Hunt and Hess grade and age (adjusted odds ratio [adjOR] 50.5, 95% confidence interval [CI] 1.3-2004.2, p = 0.034). These results remained robust when comparing the whole SAH cohort (adjOR 21.7, 95% CI 1.4-347.8, p = 0.030). CONCLUSIONS: Intraparenchymal bleeding in patients with non-traumatic SAH, in particular that involving the corpus callosum, strongly predicts functional outcome.


Prenatal alcohol exposure and thermotaxic behavior in neonatal rats.
The effect of prenatal alcohol exposure on thermotaxic behavior was investigated in 5-day-old rat pups. Pregnant dams were administered a liquid diet which contained 35% ethanol-derived calories (35% EDC) on days 6 to 20 of gestation. Two control groups were included: a liquid diet control which was pair-fed and had sucrose substituted for ethanol (0% EDC), and a group fed standard lab chow (LC) throughout pregnancy. Pups from each of these prenatal treatments were tested on a thermal gradient (thermocline). On each of 5 trails, pups were placed in the cool end of the thermocline and their position along the gradient was measured after 10 min. All prenatal treatment groups displayed thermotaxic behavior by moving towards the warm end. However, pups in the 35% EDC treatment group moved significantly further towards the warm end in the later trials. Despite their position on a warmer surface, their body temperature did not rise concurrently. Thermoregulatory deficits caused by prenatal alcohol exposure might account for these results.


Nucleosides, nucleotides and their biological applications--XIV International Roundtable. Recent Advances in Nucleosides Chemistry and Chemotherapy. 10-14 September 2000, San Francisco, CA, USA.
This satellite symposium honoring Dr Jack J Fox, provided a forum for reviewing recent advances in nucleoside research. The topics covered were: novel chemistries, applications to current problems in biology, antiviral and antitumor agents, and aspects of enzymology and mechanism of action of important nucleoside analogs.


The role of subunits in tubulin. I. Renaturation of tubulin after treatment with urea and sodium dodecyl sulfate.
Bovine brain tubulin treated with urea and SDS partially recovered colchicine binding capacity after removal of SDS in the presence of urea followed by stepwise dialysis against urea solutions of lower concentrations. Tubulin subjected to the above procedure showed the same circular dichroism spectrum between 215 and 260 nm as the native one but showed a slightly different fluorescence spectrum when excited at 290 nm.


A comparison of soil Staphylococcus aureus and fecal indicator bacteria concentrations across land uses in a Hawaiian watershed.
Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), and fecal indicator bacteria (FIB; Enterococcus spp., Clostridium perfringens) concentrations increase in Hawaiian streams and estuaries following storms and pose a health threat to recreational water users. To reduce this risk, watershed bacteria sources need to be identified for management actions. This study's goals were to identify soil bacteria sources among different land uses and to determine if their concentrations were associated with different soil properties. Soil samples were collected three times on 24 d between October 2017 and November 2018 at urban, agriculture, and native-forest land uses in the Hilo Bay watershed, Hawai'i Island, Hawai'i. Soil bacteria concentrations were quantified using culturing techniques with selective media. Staphylococcus aureus, MRSA, and FIB were present in soil from all land uses. Bacteria concentrations were highest in urban soils and lowest in native-forest soils, with up to three orders of magnitude differences among land uses. Staphylococcus aureus, MRSA, and FIB soil concentrations were positively correlated with each other and with soil temperature and pH, but inversely correlated with soil moisture and organic matter content. Our results demonstrate that soils are a watershed bacteria source and that some soil properties affect their concentrations. Identifying these sources is critical for implementing management actions to reduce pathogen loads to estuaries and transmission to recreational water users.


Antimetastatic action of the prostacyclin analogue cicaprost in experimental mammary tumors.
In breast cancer, the survival rate strongly depends on the number of lymph nodes involved. A drug with a specific inhibitory activity on lymph node and organ metastases would therefore be a candidate for adjuvant therapy after surgery. Prostacyclin and its stable analogues have been shown to interfere with certain steps of the metastatic cascade and to inhibit the number of lung colonies after i.v.-inoculation of various tumor cell lines. Our data reveal that cicaprost, a metabolically stable and orally active analogue of prostacyclin, has pronounced antimetastatic effects in a series of spontaneously metastasizing rodent tumors. In the SMT 2a and 13762 MTLn3 mammary carcinomas of the rat, cicaprost given daily from the day of tumor implantation strongly inhibits the number of lung metastases as well as lymph node weights without exerting an effect on the primary tumor. Even starting treatment when palpable primary tumors are present gives a pronounced antimetastatic activity. To demonstrate that cicaprost has an effect on metastases already settled in the respective organ, treatment was started after surgical removal of the primary tumor. In the SMT 2a tumor, a strong inhibition of the number of metastases was shown. Interestingly, a perioperative treatment schedule was also effective in both models used. As primary tumor growth in vivo or proliferation in vitro remained unchanged by cicaprost, its mode of action seems to be related to one or more mechanisms of the metastatic process. In tumor cell lines expressing a functional prostacyclin receptor, stimulated tumor cell migration is inhibited and changes of differentiation status are obvious. In conclusion, cicaprost strongly inhibits lymph node and organ metastases of spontaneously metastasizing rodent mammary tumors with a mode of action different from cytostatic or antihormonal drugs.


Antithrombotic strategies after transcatheter aortic valve implantation: A systematic review and network meta-analysis of randomized controlled trials.
Meta-analyses comparing different antithrombotic strategies were conducted to determine the optimal therapeutic regimen post transcatheter aortic valve implantation (TAVI). However, there were restricted high-quality direct comparisons across the different antithrombotic therapeutic regimens. We sought to explore the safety and efficacy of different antithrombotic therapy strategies after TAVI using network meta-analyses of randomized controlled trials (RCTs). We searched CENTRAL, PubMed, Embase and Medline through August 2021 for RCTs that directly compared different antithrombotic schemes in adults who had undergone TAVI. We conducted a pairwise and network meta-analysis measuring all-cause mortality, stroke, myocardial infarction, all bleeding and life-threatening or major bleeding events. The surface under the cumulative ranking (SUCRA) curve was estimated to rank the therapies. We evaluated the risk of bias and graded the quality of the evidence using established methods. Six RCTs of 2824 patients who underwent TAVI were analysed. The risk of all bleeding [relative risk (RR) 1.88 (1.34-2.64)] and life-threatening or major bleeding [RR 2.03 (1.27-3.24)] was significantly higher for dual antiplatelet therapy (DAPT) than single antiplatelet therapy (SAPT), whereas there was no significant difference in the risk of all-cause mortality [RR 1.01 (0.61-1.68)] between DAPT and SAPT. Oral anticoagulant (OAC) + SAPT (OACSAPT) had significantly higher rates of all bleeding and life-threatening or major bleeding events compared with SAPT ([RR 3.46 (2.23-5.36)], [RR 2.86 (1.50-5.45)]). The risk of all-cause mortality [RR 1.72 (1.14-2.59)] and all bleeding [RR 1.84 (1.38-2.44)] were significantly higher for OACSAPT than DAPT, whereas there was no significant difference in the risk of life-threatening or major bleeding events [RR 1.41 (0.89-2.23)] between DAPT and OACSAPT. There was no significant difference in stroke or myocardial infarction among the different antithrombotic strategies (SAPT, DAPT and OACSAPT). Additionally, patients receiving OACSAPT had the highest risks for all-cause mortality (SUCRA 3.5%) and life-threatening or major bleeding (SUCRA 2.3%). SAPT seemed to be superior to DAPT in terms of all-cause mortality (SUCRA SAPT: 76.7%, DAPT: 69.8%) and stroke (SUCRA 69.6%, 59.7%). Except for OACSAPT having a higher all-cause mortality than DAPT, patients who underwent TAVI had similar all-cause mortality, stroke and myocardial infarction rates among different antithrombotic regimens. Patients on SAPT had a significantly lower bleeding risk than those on DAPT and OACSAPT. Our study indicates that SAPT is the preferred therapeutic strategy when there is no indication for OAC or DAPT. Furthermore, the application of OACSAPT was ranked the worst among all antithrombotic regimens and should be averted due to an increased risk of all-cause mortality and all bleeding.


G-6PD loading of G-6PD-deficient erythrocytes.
G-6PD-deficient erythrocytes were loaded during hypotonic hemolysis with G-6PD extracted from yeast. It was shown that enzyme was really trapped into red blood cells and remained functionally active.


Cattle tick vaccines: many candidate antigens, but will a commercially viable product emerge?
The cattle tick, Rhipicephalus microplus, is arguably the world's most economically important external parasite of cattle. Sustainable cattle tick control strategies are required to maximise the productivity of cattle in both large production operations and small family farms. Commercially available synthetic acaricides are commonly used in control and eradication programs, but indiscriminate practices in their application have resulted in the rapid evolution of resistance among populations in tropical and subtropical regions where the invasive R. microplus thrives. The need for novel technologies that could be used alone or in combination with commercially available synthetic acaricides is driving a resurgence of cattle tick vaccine discovery research efforts by various groups globally. The aim is to deliver a next-generation vaccine that has an improved efficacy profile over the existing Bm86-based cattle tick vaccine product. We present a short review of these projects and offer our opinion on what constitutes a good target antigen and vaccine, and what might influence the market success of candidate vaccines. The previous experience with Bm86-based vaccines offers perspective on marketing and producer acceptance aspects that a next-generation cattle tick vaccine product must meet for successful commercialisation.


Dietary supplementation with Weissella cibaria C-10 and Bacillus amyloliquefaciens T-5 enhance immunity against Aeromonas veronii infection in crucian carp (Carassiu auratus).
With the aim to discover novel lactic acid bacteria and Bacillus strains from fish as potential probiotics to replace antibiotics in aquaculture, the present study was conducted to isolate lactic acid bacteria and Bacillus from intestinal tract of healthy crucian carp (Carassiu auratus) and largemouth bass (Micropterus salmoides) and evaluate their resistance against Aeromonas veronii. Based on the evaluation of antibacterial activity and tolerance test, one strain of lactic acid bacteria (Weissella cibaria C-10) and one strain of Bacillus (Bacillus amyloliquefaciens T-5) with strong environmental stability were screened out. The safety evaluation showed that these two strains were non-toxic to crucian carp and were sensitive to most antibiotics. In vivo study, the crucian carps were fed a basal diet supplemented with W. cibaria C-10 (C-10), B. amyloliquefaciens T-5 (T-5) and W. cibaria C-10 + B. amyloliquefaciens T-5 (C-10+T-5), respectively, for 5 weeks. Then, various immune parameters were measured at 35 days of post-feeding. Results showed both probiotics could improve the activities of related immune enzymes, immune factors and non-specific immune antibodies in blood and organs (gill, gut, kidney, liver, and spleen) of crucian carp in varying degrees. Moreover, after 7 days of challenge experiment, the survival rates after challenged with A. veronii of W. cibaria C-10 (C-10), B. amyloliquefaciens T-5 (T-5) and W. cibaria C-10 + B. amyloliquefaciens T-5 (C-10+T-5) supplemented groups to the crucian carps were 20%, 33% and 22%, respectively. Overall, W. cibaria C-10 and B. amyloliquefaciens T-5 could be considered to be developed into microecological preparations for the alternatives of antibiotics in aquaculture.


A Multiscale Agent-Based Model for the Investigation of E. coli K12 Metabolic Response During Biofilm Formation.
Bacterial biofilm formation is an organized collective response to biochemical cues that enables bacterial colonies to persist and withstand environmental insults. We developed a multiscale agent-based model that characterizes the intracellular, extracellular, and cellular scale interactions that modulate Escherichia coli MG1655 biofilm formation. Each bacterium's intracellular response and cellular state were represented as an outcome of interactions with the environment and neighboring bacteria. In the intracellular model, environment-driven gene expression and metabolism were captured using statistical regression and Michaelis-Menten kinetics, respectively. In the cellular model, growth, death, and type IV pili- and flagella-dependent movement were based on the bacteria's intracellular state. We implemented the extracellular model as a three-dimensional diffusion model used to describe glucose, oxygen, and autoinducer 2 gradients within the biofilm and bulk fluid. We validated the model by comparing simulation results to empirical quantitative biofilm profiles, gene expression, and metabolic concentrations. Using the model, we characterized and compared the temporal metabolic and gene expression profiles of sessile versus planktonic bacterial populations during biofilm formation and investigated correlations between gene expression and biofilm-associated metabolites and cellular scale phenotypes. Based on our in silico studies, planktonic bacteria had higher metabolite concentrations in the glycolysis and citric acid cycle pathways, with higher gene expression levels in flagella and lipopolysaccharide-associated genes. Conversely, sessile bacteria had higher metabolite concentrations in the autoinducer 2 pathway, with type IV pili, autoinducer 2 export, and cellular respiration genes upregulated in comparison with planktonic bacteria. Having demonstrated results consistent with in vitro static culture biofilm systems, our model enables examination of molecular phenomena within biofilms that are experimentally inaccessible and provides a framework for future exploration of how hypothesized molecular mechanisms impact bulk community behavior.


Amino acid sequence of the heavy chain of human alpha-factor XIIa (activated Hageman factor).
The amino acid sequence of the heavy chain of human alpha-factor XIIa (activated Hageman factor) was determined by automated Edman degradation using the peptides produced by chemical and enzymatic cleavages of intact factor XII and alpha-factor XIIa. Combining this sequence with the previously determined sequence of beta-factor XIIa (Fujikawa, K., and McMullen, B. A. (1983) J. Biol. Chem. 258, 10924-10933), the complete amino acid sequence of human factor XII has been established. The heavy chain of alpha-factor XIIa is composed of 353 amino acid residues containing one Asn-linked and six probable O-linked carbohydrate chains. The heavy chain of alpha-factor XIIa appears to contain four different domains including a "kringle," a "growth factor" domain, and the "type I" and "type II" domains of fibronectin. The domain organization of factor XII is analogous to those of several fibrinolytic proteins, including tissue plasminogen activator and urokinase, suggesting that factor XII belongs to the same protease subfamily as these two proteins.


Crystal structure of human epidermal kallikrein 7 (hK7) synthesized directly in its native state in E. coli: insights into the atomic basis of its inhibition by LEKTI domain 6 (LD6).
Human kallikrein 7, a major protease of human skin, has been synthesized directly in its native conformation in Escherichia coli by forcing the secretion of the newly synthesized polypeptide into the bacterial periplasm. The procedure yields a stable kallikrein 7 with highly specific activity that is inhibited efficiently by its specific inhibitor LEKTI domain 6. The protein was crystallized, and its three-dimensional structure was solved in the absence of protease inhibitors. The structure obtained agrees with that reported recently for human tissue kallikrein 7 crystallized in the presence of protease inhibitors from a preparation obtained in a baculovirus protein expression system. A model of the interaction between the protease and its inhibitor is proposed on the basis of both the three-dimensional structure of human tissue kallikrein 7 reported here and that of the LEKTI domain 6 solved previously by NMR.


Reconstitution and post-thaw storage of cryopreserved human mesenchymal stromal cells: Pitfalls and optimizations for clinically compatible formulants.
The regenerative and immunomodulatory properties of multipotent mesenchymal stromal cells (MSCs) make them an intriguing asset for therapeutic applications. An off-the-shelf approach, using pre-expanded cryopreserved allogenic MSCs, bypasses many practical difficulties of cellular therapy. Reconstitution of a MSC product away from cytotoxic cryoprotectants towards a preferred administration solution might be favorable for several indications. Variations in MSC handling accompanied by a non-standardized use of reconstitution solutions complicate a general clinical standardization of MSC cellular therapies. In this study, we aimed to identify a simple and clinically compatible approach for thawing, reconstitution, and post-thaw storage of cryopreserved MSCs. Human adipose tissue-derived MSCs were expanded in human platelet lysate (hPL) supplemented culture medium and cryopreserved using a dimethyl sulfoxide (DMSO)-based cryoprotectant. Isotonic solutions (saline, Ringer's acetate and phosphate buffered saline (PBS)) with or without 2% human serum albumin (HSA) were used as thawing, reconstitution, and storage solutions. MSCs were reconstituted to 5 × 106 MSCs/mL for evaluating MSC stability. Total MSC numbers and viability were determined using 7-aminoactinomycin D (7-AAD) and flow cytometry. For thawing cryopreserved MSCs the presence of protein was proven to be essential. Up to 50% of MSCs were lost when protein-free thawing solutions were used. Reconstitution and post-thaw storage of MSCs in culture medium and widely used PBS demonstrated poor MSC stability (>40% cell loss) and viability (<80%) after 1 h of storage at room temperature. Reconstitution in simple isotonic saline appeared to be a good alternative for post-thaw storage, ensuring >90% viability with no observed cell loss for at least 4 h. Reconstitution of MSCs to low concentrations was identified as critical. Diluting MSCs to <105/mL in protein-free vehicles resulted in instant cell loss (>40% cell loss) and lower viability (<80%). Addition of clinical grade HSA could prevent cell loss during thawing and dilution. This study identified a clinically compatible method for MSC thawing and reconstitution that ensures high MSC yield, viability, and stability. The strength of the method lies within the simplicity of implementation which offers an accessible way to streamline MSC therapies across different laboratories and clinical trials, improving standardization in this field.


c-Jun N-terminal kinase signaling in cellular senescence.
Cellular senescence leads to decreased tissue regeneration and inflammation and is associated with diabetes, neurodegenerative diseases, and tumorigenesis. However, the mechanisms of cellular senescence are not fully understood. Emerging evidence has indicated that c-Jun N-terminal kinase (JNK) signaling is involved in the regulation of cellular senescence. JNK can downregulate hypoxia inducible factor-1α to accelerate hypoxia-induced neuronal cell senescence. The activation of JNK inhibits mTOR activity and triggers autophagy, which promotes cellular senescence. JNK can upregulate the expression of p53 and Bcl-2 and accelerates cancer cell senescence; however, this signaling also mediates the expression of amphiregulin and PD-LI to achieve cancer cell immune evasion and prevents their senescence. The activation of JNK further triggers forkhead box O expression and its target gene Jafrac1 to extend the lifespan of Drosophila. JNK can also upregulate the expression of DNA repair protein poly ADP-ribose polymerase 1 and heat shock protein to delay cellular senescence. This review discusses recent advances in understanding the function of JNK signaling in cellular senescence and includes a comprehensive analysis of the molecular mechanisms underlying JNK-mediated senescence evasion and oncogene-induced cellular senescence. We also summarize the research progress in anti-aging agents that target JNK signaling. This study will contribute to a better understanding of the molecular targets of cellular senescence and provides insights into anti-aging, which may be used to develop drugs for the treatment of aging-related diseases.


Metabolomics of meat exudate: Its potential to evaluate beef meat conservation and aging.
In this study we analyzed the exudate of beef to evaluate its potential as non invasive sampling for nuclear magnetic resonance (NMR) based metabolomic analysis of meat samples. Exudate, as the natural juice from raw meat, is an easy to obtain matrix that it is usually collected in small amounts in commercial meat packages. Although meat exudate could provide complete and homogeneous metabolic information about the whole meat piece, this sample has been poorly studied. Exudates from 48 beef samples of different breeds, cattle and storage times have been studied by (1)H NMR spectroscopy. The liquid exudate spectra were compared with those obtained by High Resolution Magic Angle Spinning (HRMAS) of the original meat pieces. The close correlation found between both spectra (>95% of coincident peaks in both registers; Spearman correlation coefficient = 0.945) lead us to propose the exudate as an excellent alternative analytical matrix with a view to apply meat metabolomics. 60 metabolites could be identified through the analysis of mono and bidimensional exudate spectra, 23 of them for the first time in NMR meat studies. The application of chemometric tools to analyze exudate dataset has revealed significant metabolite variations associated with meat aging. Hence, NMR based metabolomics have made it possible both to classify meat samples according to their storage time through Principal Component Analysis (PCA), and to predict that storage time through Partial Least Squares (PLS) regression.


Photofrin as a specific radiosensitizing agent for tumors: studies in comparison to other porphyrins, in an experimental in vivo model.
The use of ionizing radiation for tumor treatment represents a well established therapeutic modality. The efficiency and selectivity of radiotherapeutic protocols can be often enhanced by the addition of specific chemical compounds that optimise the response of the tumor to the incident radiation as compared with peritumoral tissue districts. The results of this study showed that Photofrin, a porphyrin derivative which is presently used as a tumor-photosensitizing agent in photodynamic therapy (PDT), can also act as an efficient tumor radiosensitizer. To test this possibility, we used nude mice subcutaneously implanted with human bladder cancer RT4. The mice were injected with different porphyrin-type photosensitizing agents, including Photofrin, 5-aminolevulinic acid, chlorin e(6), haematoporphyrin, protoporphyrin, Zn-tetrasulphophtalocyanine, and irradiated with 5 and 15 Gy using a Siemens X-ray device. Even though all the porphyrins accumulated in significant amounts in the neoplastic lesion, only Photofrin significantly improved the response of the tumor to irradiation by increasing the doubling time of the tumor volume from 6.2 days in the untreated control group to 10.9 days in the 5 and 15 Gy-irradiated groups. The tumor response was maximal with injected Photofrin doses of 7.5 mg/kg, and was not further enhanced by injection of higher doses. Our hypothesis is, that the radiosensitizing effect of Photofrin seems to be due to some oligomeric constituents which could specifically react with radiogenerated-radicals thereby amplifying the effect of the X-ray radiation.


Distribution of fluoroquinolone MICs in Helicobacter pylori strains from Korean patients.
The aim of this study was to assess the prevalence rate of primary fluoroquinolone resistance in Helicobacter pylori isolates from Korean patients over the past 16 years. One hundred and thirty-five strains of H. pylori (34 strains in 1987, 36 in 1994 and 65 in 2003) were isolated from antral gastric mucosal biopsy specimens. The determination of MICs for the H. pylori isolates of ciprofloxacin, levofloxacin and moxifloxacin was examined by using the serial 2-fold agar dilution method. DNA sequences of the gyrA gene in fluoroquinolone-resistant strains were determined. The distribution of fluoroquinolone MICs (ciprofloxacin, levofloxacin and moxifloxacin) shifted to higher concentrations during 1987-2003. All of the levofloxacin- or moxifloxacin-resistant strains were resistant to ciprofloxacin. Sequence analysis in fluoroquinolone-resistant strains showed point mutation of the gyrA gene at A272G and G271A, indicating mutations of the codon Asp-91 in the fluoroquinolone-resistance-determining region of the DNA gyrase. These results suggest that resistance to fluoroquinolones has been increasing in the Korean population and the resistance is most likely mediated through point mutation in gyrA.


Competition between an avoidance response and a safety signal: evidence for a single learning system.
Two experiments examined competition between an instrumental avoidance response and a Pavlovian safety signal for association with omission of electric shock in a human fear conditioning paradigm. Self-reported shock expectancies and skin conductance responses were consistent with blocking of learning of the instrumental contingency by prior training of the Pavlovian contingency, and vice versa. The results support the idea that a common learning mechanism underlies both Pavlovian and instrumental conditioning. The expectancy data suggest that this learning mechanism is cognitive in nature, and that Pavlovian and instrumental learning involve external and internal attributions, respectively. The procedure may thus serve as a laboratory model for attributional processes involved in the acquisition of threat expectancies in anxiety and anxiety disorders.


Cord blood androgen levels of females from same sex and opposite sex twins - A pilot study.
Opposite-sex twins have shown behavioural and reproductive differences between females and males. These differences may be determined by higher intrauterine levels of androgens among females that were exposed to a male co-twin. The aim of this study was to compare cord blood androgen levels in females from same-sex and opposite-sex twins. A prospective study. In this pilot study, we compared cord blood androgens (DHEA-S, Δ-4 androstenedione, total testosterone-TT) and sex hormone-binding globulin (SHBG) levels in 20 females from same sex and 20 females from opposite-sex dichorionic diamniotic twins. We used generalized estimating equation (GEE) modelling to assess differences in cord blood androgens between females from same-sex twin pregnancies and females from opposite-sex twin pregnancies. Twenty opposite-sex twin pairs (female-male twins) and 20 same-sex twin pairs (female-female). Cord blood total testosterone, Δ-4 androstenedione, DHEA-S and sex hormone-binding globulin (SHBG) levels. No difference in the levels of androgens as Δ-4 androstenedione, total testosterone and SHBG was identified between females that were exposed to a female co-twin compared with females that were exposed to a male co-twin. DHEA-S levels were significantly lower among females from opposite-sex twins compared with females from same-sex twins. Our preliminary data do not support the hypothesis that females exposed to male co-twins are exposed to higher levels of androgens in utero compared with females exposed to female co-twins. Further studies are needed to explain the reported behavioural and reproductive differences among opposite-sex twins.


Child sexual abuse: victim age, victim gender, and observer gender as factors contributing to attributions of responsibility.
The purpose of this study was to investigate the effects of victim gender, and observer gender on the tendency to attribute responsibility for extrafamilial child sexual abuse to the victim and the nonoffending parents. A 2 (Victim Age) x 2 (Victim Gender) x 2 (Observer Gender) between-subjects design was employed. Undergraduate students (N = 145) read a vignette describing a sexually abusive interaction between an adult male neighbor and a child. In this vignette, the child's gender and age (6 years old, 13 years old) varied. After reading the vignette, participants used a 5-point scale to indicate the degree to which they believed the victim and the parents (a) were responsible for, (b) were to blame for, (c) caused, and (d) could have prevented the abuse. Greater responsibility was assigned to older than younger victims. Both parents were ascribed similar levels of responsibility, and were ascribed greater responsibility when the child victim was younger than older. Male observers attributed greater responsibility and causality to the victim and the parents than did female observers. The results indicate that responsibility attributions directed toward the victim and the nonoffending parents may be a function of the victim's age. In addition, the findings support previous research suggesting that male observers may tend to hold victims more responsible for their abuse than female observers. Implications for treatment and research are discussed.


[Carotid body and glomus vagale tumours (author's transl)].
Twentyfour chemodectomas (non-chromaffin paragangliomas) of the neck seen in 20 patients are presented. The investigation including angiography and the surgery in respect to risk factors and preoperative assessment is discussed. The long term results are also presented. Special note is made of the familial incidence since two twin brothers who had bilateral tumours are included.


Endovascular treatment of tiny ruptured anterior communicating artery aneurysms.
Because of its high complication rate, the endovascular treatment (EVT) of anterior communicating artery (ACoA) aneurysms less than 3 mm in maximum diameter remains controversial. We evaluated EVT of tiny ruptured ACoA aneurysms with Guglielmi detachable coils (GDCs). We treated 19 ruptured ACoA aneurysms with a maximum diameter of <or=3 mm with GDCs. The pretreatment Hunt and Hess score was grade 1 in four patients, grade 2 in six, grade 3 in six, and grade 4 in three. The patients were clinically assessed before and after treatment and with multiple angiographic follow-up studies. All EVTs were successful; there were no aneurysm perforations or any other treatment-related complications. In five patients older than 80 years the transfemoral approach was difficult, and the direct carotid approach was used. Complete and near-complete occlusion was achieved in 16 patients (84.2%) and 3 patients (15.8%), respectively. Of the 19 patients, 16 (84.2%) were followed angiographically for a median of 38.5 months (range 16-72 months). None demonstrated recanalization of the aneurysm requiring additional treatment. In 15 patients (78.9%) the final outcome was good (modified Rankin scale, mRS, score 0-2), and 3 patients (15.8%) died or suffered severe disability (mRS score 4-6). None of 18 patients who were followed clinically for a median of 39.5 months (range 17-84 months) experienced rebleeding. Even tiny ruptured ACoA aneurysms can be safely treated by EVT by expert neurointerventionalists using advanced techniques.


Defining pathogenicity of NOTCH2 variants for diagnosis of Alagille syndrome type 2 using a large cohort of patients.
Alagille syndrome (ALGS) type 2 caused by mutations in NOTCH2 has genotypic and phenotypic heterogeneity. Diagnosis in some atypical patients with isolated hepatic presentation could be missed. Using 2087 patients with paediatric liver manifestations, NOTCH2 allele frequencies, in-silico prediction, protein domains and clinical features were analysed to define the pathogenicity of NOTCH2 variants for diagnosis of ALGS type 2. Among 2087 patients with paediatric liver manifestations, significantly more NOTCH2 variants were absent in gnomAD in patients with elevated γ-glutamyltransferase (GGT) (p = .041). Significantly more NOTCH2 variants which were absent in gnomAD were located in protein functional domains (p = .038). When missense variants were absent in gnomAD and predicted to be pathogenic by at least three out of seven in-silico tools, they were found to be significantly associated with liver manifestations with elevated GGT (p = .003). Comparing this to patients with likely benign (LB) variants, the patients with likely-pathogenic (LP) variants have significantly more liver manifestations with elevated GGT (p = .0001). Significantly more patients with LP variants had extra-hepatic phenotypes of ALGS compared with those patients with LB variants (p = .0004). When NOTCH2 variants are absent in gnomAD, null variants and missense variants which were predicted to be pathogenic by at least three in-silico tools could be considered pathogenic in patients with high GGT chronic liver diseases.


STA-MCA/STA-PCA Bypass Using Short Interposition Vein Graft.
Superficial temporal artery (STA) is the mainstay of donor vessels for extra-intracranial bypass (EC-IC bypass) in cerebral revascularization. However, the typically used STA frontal or parietal branch is not always adequate in its flow-carrying capacity. In the present study, we provide an update on an alternative strategy: the use of the STA main trunk as a donor vessel, with a short vein interposition graft. Seven patients in whom the STA main trunk was used as a donor site for anastomosis of a short interposition vein graft were included. The grafts were implanted into the M2 of the middle cerebral artery for adjunctive treatment of IC anterior wall blood-blister aneurysms in two patients, for revascularization of an internal carotid artery occlusion in one patient, into the P2/3 of the posterior cerebral artery (PCA) for adjunct treatment of complex PCA aneurysms in three patients and into the P3 of PCA for adjunct treatment of basilar artery (BA) trunk giant aneurysm in one patient. All the bypasses were patent. Intraoperative flow measurements confirmed a moderate flow-carrying capacity of the STA main trunk-interposition short vein graft (20-50 ml; mean 43 ml/min). The STA main trunk has a larger diameter than the distal branch; therefore, it would be expected to have a significantly higher flow capacity than its branches. STA main trunk to proximal MCA/PCA bypass using short interposition vein grafts can provide sufficient blood flow, and may be a reasonable alternative to ECA to MCA/PCA bypass using long vein grafts.


Significance of white matter high intensity lesions as a predictor of stroke from arteriolosclerosis.
To determine whether the extent of white matter high intensity lesions (WML) on magnetic resonance imaging (MRI) is an independent predictor of risk for stroke from arteriolosclerosis, and whether serial evaluation of WML can be used to identify patients who are at risk of strokes. Prospective follow up with serial MRI scans was done in 89 patients who were either diagnosed as having symptomatic lacunar infarcts or were stroke-free, neurologically normal individuals with headache or dizziness. None had significant stenosis of major cerebral arteries or atrial fibrillation. Multivariable analysis with the Cox proportional hazards model was used to test the predictive value for subsequent stroke of risk factor status at entry and during follow up, lacunar infarction, and the extent of WML (scored from 0 to 16) on the baseline scans. During follow up (mean (SD), 51 (19) months), seven strokes occurred (five lacunar infarcts and two haemorrhages): four in nine patients with severe WML (score 9-16), and three in 40 patients with mild WML (score 1-8) (log-rank test; p < 0.005). None of 40 patients without WML experienced stroke. The extent of WML was an independent predictor of subsequent stroke (relative risk for a 1 point score increase, 1.60; 95% confidence interval, 1.02 to 2.54; p < 0.05). In three strokes among 80 patients without severe WML, two occurred in four patients with an increase in WML score during follow up, and one occurred in the other 76 patients without an increased score (p < 0.0001). Severe WML at baseline is an independent predictor of risk for stroke from arteriolosclerosis, while progression of WML during follow up may be associated with subsequent stroke in patients with initially mild WML.


Management of cuts, abrasions and lacerations.
The treatment of minor wounds makes up a significant proportion of the workload in the A&E department. Valerie Small examines the treatment options available.


Trisomy 12 mosaicism in an infertile man.
Cytological studies of peripheral blood lymphocytes from an infertile man revealed the presence of a mosaic trisomy 12. To our knowledge this has not been previously reported in patients. The clinical manifestations in this case enhance the interest of the cytological findings.


True brachial artery aneurysm: A case report and review of literature.
A true brachial artery aneurysm is a rare pathology with an incidence of 0.17% of all peripheral artery aneurysms. This pathology can manifest devastating complications if overlooked, however, a high index of suspicion coupled with a thorough history and physical allows easy diagnosis. We present a rare case of the oldest documented patient with a true brachial artery aneurysm with idiopathic etiology. An 83-year-old gentleman presented with left upper extremity pain, erythema, and swelling for 1 week. He denied trauma to the area. Examination revealed a pulsatile mass of the antecubital fossa and decreased distal pulses. Imaging illustrated a 9mm aneurysm of the brachial artery with stenosis of the radial artery and non-enhancement of the origin of the ulnar artery. The patient underwent a brachial aneurysm excision, radial and ulnar embolectomy, and brachial to ulnar and radial artery bypass. Postoperatively, palpable pulses were appreciated in the radial and ulnar arteries. Pathology demonstrated a true aneurysm. The patient's postoperative course was uneventful and follow-up 6 months later revealed normal perfusion. This case highlights the importance of maintaining a high index of suspicion coupled with a thorough history and physical examination when encountering neurovascular complaints of the upper extremities. Operative intervention even in asymptomatic patients is warranted due to a high complication rate of 33%. More research into the pathophysiology of this rare pathology is needed to further understand, prevent, or mitigate its complications.


A new technique for femoral and tibial tunnel bone grafting using the OATS harvesters in revision anterior cruciate ligament reconstruction.
Revision anterior cruciate ligament (ACL) reconstruction is becoming more frequent, especially in specialized centers, because of the large numbers of primary ACL procedures performed. In 2-stage revisions, bone grafting of the tunnels may be undertaken if the primary position was inaccurate or if osteolysis has caused widening of the tunnels. This will allow the desired placement of the new tunnels without the risk of loss of structural integrity. It is technically difficult to deliver and impact bone graft into the femoral tunnel with the standard surgical and arthroscopic instruments. We describe a new technique for femoral and tibial tunnel impaction grafting in 2-stage ACL revisions, using the OATS grafting instruments (Osteochondral Autologous Transfer System; Arthrex, Naples, FL). The appropriately sized OATS harvester is chosen 1 mm larger than the tunnel size and is used to harvest bone graft from the iliac crest through a percutaneous approach. This provides a cylindrical graft, which is delivered to the femoral tunnel through the arthroscopic portal. The inside punch of the harvester is tapped and this allows delivery of the graft in a controlled manner and its impaction into the tunnel. The same is repeated for the tibial tunnel while providing support for the proximal end of the tunnel.


A major shift of viral and nutritional risk factors affects the hepatocellular carcinoma risk among Ivorian patients: a preliminary report.
Hepatocellular carcinoma (HCC) is a major public health concern in Sub-Saharan Africa. Early research in Ivory Coast showed that chronic hepatitis B and aflatoxin B1 exposure were the two most important etiological agents of HCC in the country but, surprisingly, no survey analyzing HCC etiologies has been conducted since decades. In a preliminary report, we characterized for hepatitis B and C markers 30 consecutive cases of HCC recruited from Abidjan hospitals between June 2011 and December 2012. Nutritional and lifestyle features of patients were analyzed as well. The mean age of the patients was 53 ± 15 years with a sex ratio (M:F = 2.7). HBsAg was the most frequent viral marker in the series (63 %). All HBV isolates belonged to genotype E. With regards to regional standard, anti-HCV reached a very high level (47 %) in the present series. Hepatitis C was more frequent among patients living outside Abidjan (83 vs 23 %, P = 0.009). Patients living in Abidjan were significantly younger than individual living elsewhere in the country (48 ± 14 vs 60 ± 16 years old, P = 0.038) reflecting a possible role for local environmental pollution in tumor progression. Finally, we observed that patients born in Mandé/Gur-speaking regions (North) were younger (48 ± 14 vs 59 ± 15, P = 0.05) and consumed maize more frequently (80 vs 26 %, P = 0.009) than other patients. Interestingly, maize consumption was associated with a trend for aminotransferases elevation (mean = 1.7-1.8 fold, P = 0.06) suggesting a direct hepatic toxicity of this staple food in Ivory Coast. In conclusion, our work indicates that HCC epidemiology underwent recently major drifts in Ivory Coast.


Oxytocin response to insulin-induced hypoglycemia in obese subjects before and after weight loss.
The response of plasma oxytocin to an iv bolus injection of crystalline insulin (0.15 U/kg) was evaluated in 14 normal weight [mean body mass index (BMI) = 23] and in 9 obese (mean BMI = 42) men. Similar blood glucose decrements after insulin injection were observed in the two groups. Obese and normal weight subjects presented similar basal oxytocin levels. In both groups, oxytocin rose significantly during the insulin tolerance test (ITT); however, the peak oxytocin response in the obese men was significantly lower than in the normal weight subjects. Obese men were restudied after substantial weight loss. Basal oxytocin levels and glucose response to insulin did not change after weight reduction. The oxytocin response to the ITT was significantly higher than before slimming and did not differ from that observed in the normal weight subjects. A significant negative correlation between BMI values and oxytocin peak levels during ITT was observed in the lean controls and obese subjects (r = 0.516, p less than 0.02). These results demonstrate that in obese subjects the oxytocin secretory response during an insulin tolerance test is reduced, suggesting the existence of a hypothalamic-pituitary disorder in obesity.


Histopathology of experimental Schistosoma incognitum infection in mice following exposure to normal and irradiated cercariae.
The tissue reactions in mice, experimentally infected with normal and irradiated cercariae of S. incognitum were studied. The lesions observed in the skin, liver, lungs and the intestine of mice infected with normal cercariae are briefly described, and compared with those observed with cercariae irradiated at 3000 r of gamma rays. In general, the reactions in mice exposed to normal cercariae were more intense than in those infected with irradiated cercariae. The severity of the reactions appeared largely due to the deposition of eggs in the tissues of the mice infected with normal cercariae. The experimental evidence suggested that most of the flukes from the irradiated cercariae are destroyed in the liver by tissue reaction.