Treatment of therapy-refractory B-lineage acute lymphoblastic leukemia with an apoptosis-inducing CD19-directed tyrosine kinase inhibitor.
Seven children and eight adults with CD19+ B-lineage acute lymphoblastic leukemia, as well as one adult with chronic lymphocytic leukemia, were treated with the CD19 receptor-directed tyrosine kinase inhibitor B43-Genistein. All patients had failed previous chemotherapy regimens, and six patients had relapsed after bone marrow transplantation. B43-Genistein was administered as a 1-hour i.v. infusion at 0.1-0.32 mg/kg/day dose levels for 10 consecutive days or 3 consecutive days weekly for a total of nine doses. B43-Genistein was well tolerated by all patients with no life-threatening side effects. There were six episodes of grade 2-3 fever, two of which were clearly drug related, one episode each of grade 3 myalgia, grade 2 sinus tachycardia, and grade 2 vascular leak syndrome. There was one durable complete remission and two transient responses. Pharmacokinetic analyses in 12 patients revealed a plasma half-life of 20 +/- 5 h, mean residence time of 24 +/- 5 h, and a systemic clearance rate of 20 +/- 3 ml/h/kg. Moderate levels of human antimouse antibody (HAMA) ranging from 20-87 ng/ml were detected in the day 28 blood samples from three of nine cases examined. Treatment of these three HAMA-positive patients with a second course of B43-Genistein did not yield measurable immunoconjugate levels in the plasma, indicating that the administered B43-Genistein molecules were rapidly cleared from circulation due to the HAMA. On the basis of its acceptable toxicity profile and its ability to elicit objective responses at nontoxic dose levels, B43-Genistein may provide the basis for an effective treatment strategy for B-lineage acute lymphoblastic leukemia patients who have failed standard therapy.


Updating Phospholipase A2 Biology.
The phospholipase A2 (PLA2) superfamily contains more than 50 enzymes in mammals that are subdivided into several distinct families on a structural and biochemical basis. In principle, PLA2 has the capacity to hydrolyze the sn-2 position of glycerophospholipids to release fatty acids and lysophospholipids, yet several enzymes in this superfamily catalyze other reactions rather than or in addition to the PLA2 reaction. PLA2 enzymes play crucial roles in not only the production of lipid mediators, but also membrane remodeling, bioenergetics, and body surface barrier, thereby participating in a number of biological events. Accordingly, disturbance of PLA2-regulated lipid metabolism is often associated with various diseases. This review updates the current state of understanding of the classification, enzymatic properties, and biological functions of various enzymes belonging to the PLA2 superfamily, focusing particularly on the novel roles of PLA2s in vivo.


Safety and effectiveness of ezetimibe in liver transplant recipients with hypercholesterolemia.
Hypercholesterolemia is a common problem among transplant recipients. Despite package-insert warnings about the potential side effects of the use of statins in patients with chronic liver disease, they are often prescribed for liver transplant recipients. Unlike statins, ezetimibe acts through inhibition of enterohepatic recirculation of lipids. We report the effectiveness and safety of ezetimibe among liver transplant recipients because this has been evaluated previously only in kidney and heart transplant patients. A consecutive cohort of 25 liver graft recipients with serum low-density lipoprotein (LDL) levels > 100 mg/dL (2.5 mmol/L) after a mean (+/-standard deviation) of 55 +/- 21 months following liver transplantation received ezetimibe (10 mg orally every day) for at least 6 months. Serum lipid profiles, liver and renal function tests, and dosages and blood levels of the immunosuppression drugs at baseline, 3 months, and 6 months were prospectively collected. The overall mean age was 58 +/- 12 years, and 56% were males. Statin therapy and fibrates were already being used in 32% and 20% of recipients for elevated LDL and/or triglycerides, respectively. The immunosuppression regimen included cyclosporine in 48% of subjects, tacrolimus in 32%, sirolimus in 48%, and mycophenolate mofetil in 44%; only 12% were on oral prednisone with a maximum daily dose of 5 mg. After ezetimibe was started, an 18% reduction in LDL values was observed [at baseline, 147 +/- 35 mg/dL (3.8 +/- 0.9 mmol/L), and at 6 months, 120 +/- 31 mg/dL (3.1 +/- 0.8 mmol/L); P = 0.010]. After 6 months, an additional 32% achieved the target LDL level of <100 mg/dL. None of the remaining variables, including immunosuppression drug levels, varied significantly during ezetimibe therapy. None of the subjects required adjustments in their pharmacological dosages. One discontinued ezetimibe 3 months later because of cost, 2 subjects had minimal nausea, 1 subject had myalgias without a rise in creatine phosphokinase, and 1 subject had a transient elevation (3-5 times) in liver enzymes from baseline with increases in the total and indirect bilirubin levels. In conclusion, among liver transplant recipients, hypercholesterolemia can be effectively treated with ezetimibe with few side effects and no interaction with immunosuppressive regimens.


Transcriptional response of Leptospira interrogans to iron limitation and characterization of a PerR homolog.
Leptospirosis is a globally significant zoonosis caused by Leptospira spp. Iron is essential for growth of most bacterial species. Since iron availability is low in the host, pathogens have evolved complex iron acquisition mechanisms to survive and establish infection. In many bacteria, expression of iron uptake and storage proteins is regulated by Fur. L. interrogans encodes four predicted Fur homologs; we have constructed a mutation in one of these, la1857. We conducted microarray analysis to identify iron-responsive genes and to study the effects of la1857 mutation on gene expression. Under iron-limiting conditions, 43 genes were upregulated and 49 genes were downregulated in the wild type. Genes encoding proteins with predicted involvement in inorganic ion transport and metabolism (including TonB-dependent proteins and outer membrane transport proteins) were overrepresented in the upregulated list, while 54% of differentially expressed genes had no known function. There were 16 upregulated genes of unknown function which are absent from the saprophyte L. biflexa and which therefore may encode virulence-associated factors. Expression of iron-responsive genes was not significantly affected by mutagenesis of la1857, indicating that LA1857 is not a global regulator of iron homeostasis. Upregulation of heme biosynthetic genes and a putative catalase in the mutant suggested that LA1857 is more similar to PerR, a regulator of the oxidative stress response. Indeed, the la1857 mutant was more resistant to peroxide stress than the wild type. Our results provide insights into the role of iron in leptospiral metabolism and regulation of the oxidative stress response, including genes likely to be important for virulence.


Atypical presentations of celiac disease.
Celiac disease (CD) has a wide variety of clinical presentations; together with the "classical form", in which the intestinal symptomatology is prevalent, there are "atypical forms" with predominating extra-intestinal clinical features, and the "silent form", with no clinical symptom. The "atypical forms" of the disease are characterized by few or no gastrointestinal symptoms, and predominating extra-intestinal features such as neurologic, dermatologic, hematologic, endocrinologic, reproductive, renal, psychiatric, skeletal, and liver involvement(s). Silent presentation of CD may be identified through screening of high-risk groups. Today, it is well known that CD might account for several chronic health issues, so it is essential for healthcare professionals to have a high level of suspicion for the atypical presentations of CD.


eGrants: University of Cincinnati's Digital grants preparation, workflow routing, and submission system.
Overabundance of largely unorganized and unfiltered information is the greatest information problem facing the faculty, staff, and students of the University of Cincinnati (UC). The goal of UC's IAIMS operations grant is to provide individuals with information that is organized, filtered, context -appropriate, and presented in personalized formats. This presentation will focus on one module, eGrants, of UC's IAIMS research administration system,which will fully digitize the pre-award, post-award, and compliance phases of the grant lifecycle . eGrants will streamline and reduce errors in the grant preparation, routing, and submittal process thus raising the overall quality of and consistency of grant submittals and greatly reducing the time and the cost of grant preparation.


Cervix Cancer in Sub-Saharan Africa: An Assessment of Cervical Cancer Management.
Underdeveloped nations carry the burden of most cervical cancer, yet access to adequate treatment can be challenging. This report assesses the current management of cervical cancer in sub-Saharan Africa to better understand the needs of underdeveloped nations in managing cervical cancer. A pre- and postsurvey was sent to all centers participating in the Cervical Cancer Research Network's 4th annual symposium. The pre- and postsurvey evaluated human papillomavirus and HIV screening, resources available for workup and/or treatment, treatment logistics, outcomes, and enrollment on clinical trials. Descriptive analyses were performed on survey responses. Twenty-nine centers from 12 sub-Saharan countries saw approximately 300 new cases of cervical cancer yearly. Of the countries surveyed, 55% of countries had a human papillomavirus vaccination program and 30% (range, 0%-65%) of women in each region were estimated to have participated in a cervical cancer screening program. In the workup of patients, 43% of centers had the ability to obtain a positron emission tomography and computed tomography scan and 79% had magnetic resonance imaging capabilities. When performing surgery, 88% of those centers had a surgeon with an expertise in performing oncological surgeries. Radiation therapy was available at 96% of the centers surveyed, and chemotherapy was available in 86% of centers. Clinical trials were open at 4% of centers. There have been significant advancements being made in screening, workup, and management of patients with cervical cancer in sub-Saharan Africa; yet, improvement is still needed. Enrollment in clinical trials remains a struggle. Participants would like to enroll patients on clinical trials with Cervical Cancer Research Network's continuous support.


Early feeding and early life housing conditions influence the response towards a noninfectious lung challenge in broilers.
Early life conditions such as feed and water availability immediately post hatch (PH) and housing conditions may influence immune development and therefore immune reactivity later in life. The current study addressed the consequences of a combination of these 2 early life conditions for immune reactivity, i.e., the specific antibody response towards a non-infectious lung challenge. Broiler chicks received feed and water either immediately p.h. or with a 72 h delay and were either reared in a floor or a cage system. At 4 weeks of age, chicks received either an intra-tracheally administered Escherichia coli lipopolysaccharide (LPS)/Human Serum Albumin (HUSA) challenge or a placebo, and antibody titers were measured up to day 14 after administration of the challenge. Chicks housed on the floor and which had a delayed access to feed p.h. showed the highest antibody titers against HuSA. These chicks also showed the strongest sickness response and poorest performance in response to the challenge, indicating that chicks with delayed access to feed might be more sensitive to an environment with higher antigenic pressure. In conclusion, results from the present study show that early life feeding strategy and housing conditions influence a chick's response to an immune challenge later in life. These 2 early life factors should therefore be taken into account when striving for a balance between disease resistance and performance in poultry.


Neurofilament light chain as a biomarker of neuronal damage in children with malaria.
Malaria can cause brain injury. Neurofilament light chain (NfL) is a biomarker of neuronal damage. Here we examined longitudinal plasma NfL levels in children aged 1-12 years with uncomplicated and severe malaria from Mozambique. NfL levels were similar in all malaria cases at hospital admission. However, levels increased over time and the increment was significantly higher in severe malaria cases with neurological manifestations (i.e., coma, impaired consciousness, or repeated seizures). NfL may be useful to identify and quantify brain injury in malaria.


Pharmacological profiles of CS-622, a novel angiotensin converting enzyme inhibitor.
CS-622 is a prodrug type ACE inhibitor with a thiazepin ring. Its active form, CS-622 diacid, was slightly more potent than enalaprilat in inhibiting ACE isolated from rabbit lung. The inhibitory potency of CS-622 diacid on isolated rat aorta was 3 times that of enalaprilat. The inhibitory action of enalaprilat was abolished quickly by washing the aortic strip with drug-free solution, whereas that of CS-622 diacid was abolished only slowly. This difference suggests that CS-622 diacid binds to vascular ACE more firmly than enalaprilat. By oral administration, CS-622 was 3 times more potent than enalapril, and its onset of action was faster than that of enalapril, suggesting that the conversion of CS-622 to its active diacid occurs faster than the conversion of enalapril. Although CS-622 diacid was only slightly more potent than enalaprilat by intravenous administration, it had a longer duration than enalaprilat. Elimination of renal excretory function potentiated the action of captopril but not that of CS-622, suggesting that unlike captopril, only a small portion of CS-622 is excreted through the kidney.


Glycohaemoglobin measurement: methodological differences in relation to interference by urea.
The aim of this study was to investigate the agreement between a cation-exchange HPLC method and a boronate affinity method of measuring glycohaemoglobin (HbA1c), with particular reference to the effect of elevated urea concentration. HbA1c was measured by both methods in samples from 75 subjects who were classified as diabetic with normal (n=36) or abnormal (n=12) renal function, and non-diabetic with normal (n=8) or abnormal (n=19) renal function. Urea was found to cause a clinically significant interference in the HPLC method at a level > or =17.0 mmol/l. Each increase of 1 mmol/l urea in serum was associated with an absolute increase of 0.04% in the HbA1c value as measured by the HPLC method. The boronate affinity method for HbA1c did not appear to be affected by elevated urea concentration. There was significant correlation (r=0.97, p<0.001) between HbA1c results obtained by the two methods, however, results obtained by the boronate affinity method were generally lower. The discrepancy between results obtained by the two methods was particularly marked in uraemic samples from diabetic subjects, as the HPLC/boronate affinity difference increased as the HbA1c increased and also as the urea concentration increased. Results indicate that blood from diabetic patients with renal failure may give erroneously high HbA1c values by HPLC. Results also highlight the importance of choosing appropriate clinical samples and statistical techniques when evaluating or comparing test methods.


MID-TERM ONCOLOGICAL OUTCOME AND TECHNICAL MODIFICATIONS FOR LAPAROSCOPIC RADICAL CYSTECTOMY AT OUR INSTITUTION: 60 CASES ANALYSIS.
(Objective) Although laparoscopic radical cystectomy (LRC) is becoming a standard care for invasive and high-risk non-invasive bladder cancer in Japan, the data about mid-and long-term oncological outcome is still lacking. We previously reported our initial experience of LRC compared to open radical cystectomy. In this study, we evaluated mid-term oncological outcome for LRC by updating our clinical data. In addition, we evaluated the effect of technical modifications for LRC. (Patients and methods) From March 2005 to September 2015, 60 patients underwent LRC at our institution. Treatment outcomes including surgical and oncological outcomes were analyzed. We also assessed the effect of technical modifications between first 30 cases and second 30 cases as to blood loss, operating time and complication rate. (Results) The overall complication rate was 47%, including 18% serious complications (Clavien score 3 or greater). The 5-year recurrence-free survival, cancer-specific survival, and overall survival were 56.2%, 74.4%, and 63.6%, respectively. The recurrence occurred in 19 (32%) cases, including distant metastasis in 12 (20%) cases, local recurrence in 6 (10%) cases, and both in 1 (2%) cases. As for the effect of technical modifications for LRC, the blood loss decreased and postoperative recovery was faster in second 30 cases. (Conclusion) These results indicate that LRC could be performed safely with acceptable oncological outcomes.


Characterization of cell-banking parameters for the cryopreservation of mammalian cell lines in 100-mL cryobags.
This article describes a cell banking process for rBHK cell lines in 100-mL cryobags. As the use of larger volume cell banks requires greater cell numbers and longer preparation time, extensive characterization of key process parameters beyond the conventional ranges was performed to support a cGMP banking process. All experiments were conducted using two recombinant BHK21 cell lines, one of them cotransfected with Hsp70. The results show that the entire cell banking process for these BHK cell lines can be performed at room temperature. A DMSO exposure time up to 5 h either directly in a bioreactor or in shaker flasks did not result in any significant negative effect after cell thaw, when the cryocontainers were frozen immediately after filling. Extensive characterization did not indicate any significant apoptotic effects after thaw. However, the Hsp70 cotransfected cell line did show a slightly better protection from potential cryopreservation-induced apoptosis. Surprisingly, it was found that cells transferred into cryobags showed a low recovery rate after thaw if the incubation time exceeded 1.5 h before freezing. Additional experiments confirmed that the DMSO exposure time inside the cryocontainer in contrast to the DMSO exposure in a reactor or shaker flasks is much more critical. The cryobag cell banking process should therefore be performed within a 1(1/2)-2 h window; a banking process for vials should not exceed 2(1/2) h.


Interstitial cells of Cajal and Auerbach's plexus. A scanning electron microscopical study of guinea-pig small intestine.
Interstitial cells of Cajal (ICC) appear to be involved in the regulation of intestinal motility, probably as pacemaker cells. We investigated the complex organization of ICC associated with Auerbach's plexus of guinea-pig small intestine in the scanning electron microscope. The plexus was exposed by microdissection of zinc iodide/osmic acid stained tissue. After separation of the muscle layers by microdissection alone, the exposed Auerbach's plexus was seen to be covered by a smooth mat of reticular fibrils, thin enough to allow the detailed examination of the intact nerve plexus and interstitial tissue. ICC were distinguished as small, ovoid cell bodies from which 2-5 long, branching, roughly cylindrical processes emerge, associating to form a complex network. Characteristically, ICC processes participated in the formation of small bundles along their course, individual processes passing from one bundle to another. Cell bodies and processes of ICC were intimately associated with tertiary nerves of Auerbach's plexus. Axons were identified and distinguished these from ICC processes by their varicose structure and by th smaller diameters as compared with ICC processes. We found no single axons in our material. The characteristic morphology of ICC clearly distinguished these as a separate cell population different from neurons, glial cells, fibroblasts, and smooth muscle cells. After removal of the mat of reticular fibrils by chemical digestion the detailed organization of the interstitial tissue was preserved. Macrophage-like cells were previously demonstrated by other techniques to constitute a constant and rather dense population of cells in the studied location. As an indication that we preserve the full complement of interstitial cells by our technique, these macrophage-like cells wer for the first time identified in material processed for scanning electron microscopy. The cells had characteristically irregular cell surfaces with short, veil-like, folded extensions intertwined between the other cells in the interstices. Our study establishes an improved correlation between results obtained by the application of scanning electron microscopy to dissected tissue and results from light and transmission electron microscopy of the intact tissue.


Evaluation of cucurbitacin-based gustatory stimulant to facilitate cucumber beetle (Coleoptera: Chrysomelidae) management with foliar insecticides in melons.
The bitter plant-derived compounds cucurbitacins are known to stimulate feeding of adult cucumber beetles (Coleoptera: Chrysomelidae). A cucurbitacin-based gustatory stimulant applied as a flowable bait combined with either spinosad or carbaryl was compared with foliar sprays of spinosad and carbaryl for controlling two cucumber beetle species (Diabrotica undecimpunctata undecimpunctata Mannerheim and Acalymma trivittatum Mannerheim) in honeydew melons (Cucumis melo L.). Field studies were conducted on the University of California-Davis plant pathology farm in 2008 and 2009. Beetle densities after applications and fruit damage from beetle feeding were compared among treatments. In addition, beetle survival was compared within field cages placed over the treated foliage infested with beetles. Using all three measures of efficacy, we determined that the addition of cucurbitacin bait had no effect on the level of cucumber beetle control with carbaryl in either 2008 or 2009. In both years, spinosad did not significantly reduce cucumber beetle densities in either field cages or field plots and did not reduce fruit damage relative to the untreated control. The addition of the bait to spinosad did not improve its efficacy. A laboratory bioassay of the spinosad formulation used in the field showed it had significant lethal effects on adults of both cucumber beetle species. Results indicated that the bait formulation used did not improve cucumber beetle control but may benefit from the addition of floral attractants or using a different type of cucurbitacin.


Accelerated landings in stingless bees are triggered by visual threshold cues.
Most flying animals rely primarily on visual cues to coordinate and control their trajectory when landing. Studies of visually guided landing typically involve animals that decrease their speed before touchdown. Here, we investigate the control strategy of the stingless bee Scaptotrigona depilis, which instead accelerates when landing on its narrow hive entrance. By presenting artificial targets that resemble the entrance at different locations on the hive, we show that these accelerated landings are triggered by visual cues. We also found that S. depilis initiated landing and extended their legs when the angular size of the target reached a given threshold. Regardless of target size, the magnitude of acceleration was the same and the bees aimed for the same relative position on the target suggesting that S. depilis use a computationally simple but elegant 'stereotyped' landing strategy that requires few visual cues.


Ocular myocysticercosis: an unusual case of ptosis.
Cysticercosis is common in endemic countries like India. It can have various clinical manifestations depending on the tissue involved. It refers to a parasitic infestation by Cysticercus cellulosae, the larval form of the pork tapeworm or Taenia solium. To report an unusual case of ocular cysticercosis involving the levator palpebrae superioris and superior rectus muscle of the right eye. A young, male adult was diagnosed by Magnetic Resonance Imaging (MRI) scan of the skull and orbit to have right-sided ocular cysticercosis. The patient was treated with oral prednisolone and albendazole, to which he showed a significant improvement. Ocular myocysticercosis can be diagnosed by MRI and be treated medically with steroid and albendazole.


[Surgical treatment of heart echinococcosis].
Echinococcosis of the heart is a rare but dangerous for life disease, very difficult for diagnosis. 5 patients with echinococcosis of the heart were examined, 2 were operated. Introduction into clinical practice of complex echocardiography contributed to precise diagnosis. The viability of the parasite was determined after application of the latex-test. Defection of the living echinococcus parasites in the heart was indication for surgery. Removal of the echinococcus from the myocardium of the left ventricle in 1 patient was carried out without artificial circulation and was accompanied by a significant risk, the complete excision of fibrous capsula being impossible. Intraventricular location of the echinococcus cyst in the other patient has required artificial circulation and cardioplegia. Intraventricular cyst was successfully and radically removed after preliminary sterilization by glycerine solution.


An Improved Trilinear Model-Based Angle Estimation Method for Co-Prime Planar Arrays.
Angle estimation methods in two-dimensional co-prime planar arrays have been discussed mainly based on peak searching and sparse recovery. Peak searching methods suffer from heavy computational complexity and sparse recovery methods face some problems in selecting the regularization parameters. In this paper, we propose an improved trilinear model-based method for angle estimation for co-prime planar arrays in the view of trilinear decomposition, namely parallel factor analysis. Due to the principle of trilinear decomposition, our method does not require peak searching and can conduct auto-pairing easily, which can reduce the computational loads and avoid parameter selection problems. Furthermore, we exploit the virtual array concept of the whole co-prime planar array through the cross-correlation matrix obtained from the received signal data and present a matrix reconstruction method using the Khatri⁻Rao product to tackle the matrix rank deficiency problem in the virtual array condition. The simulation results show that our proposed method can not only achieve high estimation accuracy with low complexity compared to other similar approaches, but also utilize limited sensor number to implement the angle estimation tasks.


Distribution and visualisation of chlorhexidine within the skin using ToF-SIMS: a potential platform for the design of more efficacious skin antiseptic formulations.
In order to increase the efficacy of a topically applied antimicrobial compound the permeation profile, localisation and mechanism of action within the skin must first be investigated. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used to visualise the distribution of a conventional antimicrobial compound, chlorhexidine digluconate, within porcine skin without the need for laborious preparation, radio-labels or fluorescent tags. High mass resolution and high spatial resolution mass spectra and chemical images were achieved when analysing chlorhexidine digluconate treated cryo-sectioned porcine skin sections by ToF-SIMS. The distribution of chlorhexidine digluconate was mapped throughout the skin sections and our studies indicate that the compound appears to be localised within the stratum corneum. In parallel, tape strips taken from chlorhexidine digluconate treated porcine skin were analysed by ToF-SIMS to support the distribution profile obtained from the skin sections. ToF-SIMS can act as a powerful complementary technique to map the distribution of topically applied compounds within the skin.


Hepatocellular carcinoma after danazol therapy.
Danazol, an inhibitor of pituitary gonadotropin, has been proposed in the treatment of systemic lupus erythematosus (SLE). We report the case of a female patient with SLE in whom a hepatocellular carcinoma was discovered after 4 years of treatment with danazol. Except for 3 days of hypochondrium pain, there were neither clinical signs of liver tumor nor biological abnormalities. An ultrasonography showed 2 tumors of the liver. At histological examination after surgery, one of the tumors was found to be a benign adenoma, while the other was a well differentiated hepatocellular carcinoma. When longterm danazol therapy is required, ultrasonography may be useful for early tumor detection.


Stalker profiles with and without protective orders: reoffending or criminal justice processing?
Research indicates that stalking is an extension of intimate partner violence. The overall purpose of this study was to better understand stalkers by examining the association between a protective order history and the court's processing of subsequent stalking, and to examine patterns of reoffending. This study examined a sample of 346 males who were charged with stalking in 1999 in one state. Subjects were partitioned into three groups: (1) males without protective orders; (2) males with one prior protective order; and (3) males with two or more prior protective orders. Almost two-thirds of the stalkers had a protective order against them at some point in the study, suggesting that stalking is associated with intimate partner violence. Results also found a linear trend with many of the criminal justice involvement variables and protective order history prior to 1999. Those charged with first-degree stalking were more likely to be found guilty initially, and about one-third of all three study groups had the initial felony stalking charge amended. Of those charged with second-degree stalking, only 7% of the group with two or more protective orders was initially found guilty, which was substantially less than the other two groups. And, when all the amendment dispositions were considered, there were no significant differences by group in guilty and dismissed dispositions for the index stalking charge. Further, consistent with previous criminal justice involvement, the group with two or more protective orders was more likely to have subsequent felony charges than the other two groups. Implications are discussed.


Oral bioavailability and in vitro stability of pivampicillin, bacampicillin, talampicillin, and ampicillin in horses.
To determine the oral bioavailabilities of 3 ampicillin esters (pivampicillin, bacampicillin, and talampicillin) and ampicillin sodium, and to determine in vitro stability of the ampicillin esters in ileal contents (pH 8.3 to 8.5). A crossover design to administer the 4 drugs orally, and ampicillin i.v. to all horses in the study. 4 healthy adult horses. The drugs were administered intragastrically to the horses at a dosage equimolar to 15 mg of ampicillin/kg of body weight. Also, ampicillin sodium was administered i.v. at the same dosage. Blood samples were taken up to 12 hours after drug administration, and ampicillin concentrations in plasma were determined. For the in vitro study, the ampicillin esters were incubated at 37 C in ileal contents obtained from ponies with cecal fistulas. After incubation, the remaining intact ester and the formed ampicillin were measured. Absolute oral bioavailability was 31, 39, 23, and 2% for pivampicillin, bacampicillin, talampicillin, and ampicillin sodium, respectively. In the in vitro study, 90% decomposition of the ester took place in 30, 60, and 5 minutes, for pivampicillin, bacampicillin, and talampicillin, respectively. Pivampicillin and bacampicillin are promising candidates for oral antibiotic treatment of horses. The rapid decomposition of ampicillin esters is caused by chemical hydrolysis at the high pH of equine ileal contents.


[Pigs led by rope].
Up to the midth of the 20th century in central europa single pigs were led by a rope, fixed on a hindleg. This technique can be proved back by pictures to antique. As shown by several illustrations this form was customary during Middle Ages and later.


The psychiatric presentation of fragile x: evolution of the diagnosis and treatment of the psychiatric comorbidities of fragile X syndrome.
Fragile X syndrome (FXS) is the leading inherited cause of mental retardation and autism spectrum disorders worldwide. It presents with a distinct behavioral phenotype which overlaps significantly with that of autism. Unlike autism and most common psychiatric disorders, the neurobiology of fragile X is relatively well understood. Lack of the fragile X mental retardation protein causes dysregulation of synaptically driven protein synthesis, which in turn causes global disruption of synaptic plasticity. Thus, FXS can be considered a disorder of synaptic plasticity, and a developmental disorder in the purest sense: mutation of the FMR1 (fragile X mental retardation 1) gene results in abnormal synaptic development in response to experience. Accumulation of this abnormal synaptic development, over time, leads to a characteristic and surprisingly consistent behavioral phenotype of attention deficit, hyperactivity, impulsivity, multiple anxiety symptoms, repetitive/perseverative/stereotypic behaviors, unstable affect, aggression, and self-injurious behavior. Many features of the behavioral and psychiatric phenotype of FXS follow a developmental course, waxing and waning over the life span. In most cases, symptoms present as a mixed clinical picture, not fitting established diagnostic categories. There have been many clinical trials in fragile X subjects, but no placebo-controlled trials of adequate size or methodology utilizing the most commonly prescribed psychiatric medications. However, large and well-designed trials of investigational agents which target the underlying pathology of FXS have recently been completed or are under way. While the literature offers little guidance to the clinician treating patients with FXS today, potentially disease-modifying treatments may be available in the near future.


Allograft reconstruction of the acetabulum after resection of stage-IIB sarcoma. Intermediate-term results.
Seventeen consecutive patients were managed with an allograft reconstruction of the pelvis (including the acetabulum) following resection of a stage-IIB bone sarcoma during a twelve-year period. The initial diagnosis was chondrosarcoma in nine patients, osteosarcoma in six, Ewing sarcoma in one, and leiomyosarcoma in one. All patients who had osteosarcoma or Ewing sarcoma received chemotherapy preoperatively and postoperatively. Fifteen patients were managed with an allograft-total hip prosthesis composite. Two patients initially were managed with an osteoarticular allograft without a prosthesis, but one had a subsequent revision to an allograft-implant composite. Four patients died with an intact allograft reconstruction. Eight patients survived with an intact allograft reconstruction, and they were followed for at least four years (mean, seven years; maximum, fourteen years). All but one was able to walk in the community with one or two canes at the time of the latest follow-up. There was a high rate of local recurrence, which occurred in three of the seventeen patients, and of infection, which developed in two patients. The five patients had a subsequent hindquarter amputation or removal of the allograft. The mean functional score (and standard deviation), according to the rating system of the Musculoskeletal Tumor Society, was 65 +/- 21.16 per cent (median, 70 per cent; range, 13 to 87 per cent) for the thirteen patients who were thus evaluated. Preservation of the limb and reconstruction with an allograft may be considered as an alternative to hindquarter amputation in carefully selected patients who have a bone sarcoma involving the acetabulum. However, patients who have a high-grade bone sarcoma must be warned that there is a substantial risk of local recurrence or infection. In the present series, more than half of the patients either died or had failure of the reconstruction.


Acoustic radiation force on a compressible spheroid.
The acoustic radiation force on a compressible spheroid is calculated using expansions of the scattered field in terms of both spherical and spheroidal wave functions that are matched analytically in the far field. There is no restriction on the size or impedance of the spheroid, the structure of the incident field, or the orientation of the spheroid with respect to the incident field. The form of the solution is the same as that developed previously for the radiation force on an elastic sphere, which is a summation of terms involving products of the coefficients in spherical wave expansions of the incident and scattered fields. Spheroidal wave expansions are employed to satisfy the boundary conditions and obtain the scattering coefficients. While the scattering coefficients must be obtained numerically for compressible spheroids, explicit expressions in terms of radial wave functions are available for spheroids with rigid or free surfaces. Results are compared with available analytical expressions for various limiting cases. The theoretical framework may be extended to objects of arbitrary shape.


Interaction of Calcium Carbonate with Nanobubbles Produced in an Alternating Magnetic Field.
Nanobubbles have been widely studied for their use in water treatments. Conventional methods for producing nanobubbles require significantly high levels of electric power. A system that involves inducing an alternative magnetic field (AMF) in flowing water has been developed, which has relatively low power requirements compared to other methods. Experimental results are presented that indicate nanobubbles are generated by this AMF system. These results include ζ potential measurements in deionized water, light scattering observations, and nanoparticle tracking analysis (NTA) measurements of object size and relative scattering intensity for water containing 5 × 10-4 M CaCO3. The NTA results also suggest the formation of nanobubble-nanoparticle clusters. Finally, an earlier work is reviewed which demonstrated that this AMF treatment led to the removal of tubercles on the inner walls of pipe samples. This prior result is discussed in light of the present evidence of nanobubble formation and a hypothesis is proposed based on the dissolution of CaCO3 as a result of nanobubble-nanoparticle clustering.


A Comprehensive Review of the Superficial Anterior Atlanto-Occipital Ligament of the Craniocervical Junction.
This paper aimed to better describe the anatomy of the superficial anterior atlanto-occipital ligament of the craniocervical junction and discuss this ligament's potential function and clinical implications. A broad literature review on the anatomical features and findings of the superficial anterior atlanto-occipital ligament was performed. The superficial anterior atlanto-occipital ligament is located anterior to the anterior atlanto-occipital membrane. However, the physiological role of the superficial anterior atlanto-occipital ligament is still unclear due to a lack of anatomical and biomechanical studies although one study has suggested that this ligament is a secondary stabilizer of the craniocervical junction. Further studies are needed to clarify the function and anatomy of the superficial anterior atlanto-occipital ligament.


Clinical Performance and Analytical Sensitivity of Three SARS-CoV-2 Nucleic Acid Diagnostic Tests.
Hundreds of RT-qPCR kits are available in the market for SARS-CoV-2 diagnosis, some of them with emergency use authorization (EUA) by the Food Drug Administration (FDA) or their country of origin agency, but also many of them without any independent clinical performance evaluation. We performed a clinical evaluation for two Chinese SARS-CoV-2 RT-PCR kits available in South America, COVID-19 Nucleic Acid Test Kit (eDiagnosis Biomedicine, Wuhan, China) and 2019-nCoV Nucleic Acid Diagnostic Kit (Sansure Biotech, Changsha, China), for RT-qPCR SARS-CoV-2 diagnosis using the FDA EUA 2019-nCoV CDC kit (IDT, Coralville, IA) as gold standard. We found an excellent clinical performance and analytical sensitivity for both kits with sensitivity values of 100% and 95.3% and estimated limit of detection of 500 copies/mL and 1,000 copies/mL, for eDiagnosis and Sansure Biotech kits, respectively. COVID-19 Nucleic Acid Test Kit (eDiagnosis) and 2019-nCoV Nucleic Acid Diagnostic Kit (Sansure Biotech) are both made in China and hold EUA by the Chinese CDC. Also, Sansure Biotech kit has EUA by the FDA. In conclusion, our results endorse the use of these two commercially available kits imported to Ecuador for SARS-CoV-2 diagnosis, as they had the similar clinical performance as the gold standard from the CDC.


Interactions of putatively irreversible antagonists with beta 1- and beta 2-adrenergic receptors.
Three compounds that have been suggested to irreversibly inactivate beta-adrenergic receptors were studied: NHNPNBE [N-(2-hydroxy-3-[1-napthoxy]-propyl)-N-bromoacetylethylenediami ne], BAAM (bromoacetylalprenololmenthane), and Ro 3-7894 [1-(5-chloracetylaminobenzfuran-2-yl)-2-isopropylaminoethanol++ +]. Membranes of rat cerebral cortex were used as a source of predominantly beta 1-adrenergic receptors and membranes of rat cerebellum were used as a source of predominantly beta 2-adrenergic receptors. Beta-Adrenergic receptor binding sites were studied by Scatchard analysis of saturation isotherms of specific [125I]-pindolol ([125I]PIN) binding. NHNPNBE added to the incubation medium competitively inhibited specific [125I]PIN binding in both cerebellum and cerebral cortex with KI values of 1-2 microM in each tissue. After washout of membranes pretreated with NHNPNBE for 30 min at 37 degrees, no loss of specific [125I]PIN binding sites was observed in either cerebellum or cortex except at very high concentrations (30-100 microM). Ro 3-7894 caused a simple competitive inhibition of specific [125I]PIN binding in rat cerebellar membranes with a KI of approximately 14 microM, an effect which was reversed completely by washing. In cerebral cortex, Ro 3-7894 added to the incubation medium apparently decreased the density of [125I]PIN binding sites with an IC50 around 1 microM. This effect was reversed after washing the membranes twice. However, in the presence of Ro 3-7894 some Scatchard plots showed a slight curvature. Further saturation of the [125I]PIN binding sites in cerebral cortex showed that the inhibition by Ro 3-7894 was competitive but with a high- and low-affinity component, consistent with Ro 3-7894 being a beta 1-selective competitive antagonist. Ro 3-7894 was also beta 1-selective in other tissues. BAAM added to the incubation medium competitively inhibited specific [125I]PIN binding in both cerebellum and cortex with KI values of 0.006 to 0.03 microM, but was about 5-fold more potent in cerebellum. After treatment of membranes with higher concentrations of BAAM for 30 min at 37 degrees and washing twice, there was a dose-dependent decrease in the density of specific [125I]PIN binding sites with IC50 values of approximately 0.3 microM in both tissues. Similar effects were observed in rat heart. These data suggest that NHNPNBE is a simple competitive antagonist at both beta 1- and beta 2-adrenergic receptors except at very high concentrations. Ro 3-7894 is a beta 1-selective competitive antagonist with no apparent irreversible effects.(ABSTRACT TRUNCATED AT 400 WORDS)


Determinants of health-related quality of life in long-term survivors of Hodgkin's lymphoma.
In this study health-related quality of life (HRQL) in long-term survivors of Hodgkin's lymphoma (HL) was evaluated and the findings were analyzed using a conceptual model developed by Wilson and Cleary. A better understanding of the relationships between the variables explaining HRQL may improve care and rehabilitation of HL patients. The populations were long-term survivors of HL (n = 121) and a control group (n = 236). Participants were approached with one semi-structured interview, an extended version of the Schedule for the Evaluation of Individual Quality of Life - Direct Weighting (SEIQoL-DW) and three standardized questionnaires: Hospital Anxiety and Depression (HAD) scale, Short Form 12 health survey questionnaire (SF-12) and Sense of Coherence (SOC) scale. No differences regarding the mean scores were found between the HL survivors and the controls except for the SF-12, where the patients considered themselves to be in poorer physical health than the controls (p < 0.01). Even though physical health was diminished, patients did not evaluate overall QoL worse compared to the controls. The major determinants of perception of general QoL were self-rated physical and mental health as well as SOC. The HRQL of persons who have survived a median of 14 years with HL is similar to that of controls.


Update on Dual Antiplatelet Therapy for Secondary Stroke Prevention.
Aspirin is recommended for patients with acute ischemic stroke within 24 hours of symptom onset. It may be beneficial for dual antiplatelet therapy including clopidogrel and aspirin to be administered in patients with minor stroke or transient ischemic attack for early secondary prevention, however, bleeding risk remains uncertain. This article will review the published literature concerning the role of dual antiplatelet therapy for secondary stroke prevention with focus on balancing both risk and benefit.


Single Nucleotide Polymorphisms in IL8 and TLR4 Genes as Candidates for Digital Dermatitis Resistance/Susceptibility in Holstein Cattle.
Relatedness between single nucleotide polymorphisms in IL8 and TLR4 genes and digital dermatitis resistance/susceptibility was investigated in seventy Holstein dairy cows. Animals were assigned into two groups, affected group (n = 35) and resistant group (n = 35) based on clinical signs and previous history of farm clinical records. Blood samples were collected for DNA extraction to ampliy fragments of 267-bp and 382-bp for IL8 and TLR4 genes, respectively. PCR-DNA sequencing revealed three SNPs in each of IL8 and TLR4 genes. The identified SNPs associated with digital dermatitis resistance were C94T, A220G, and T262A for IL8 and C118T for TLR4. However, the G349C and C355A SNPs in TLR4 gene were associated with digital dermatitis susceptibility. Chi-square analysis for comparison the distribution of all identified SNPs in both IL8 and TLR4 genes between resistant and affected animals showed no significant variation among the identified SNPs in IL8 gene. Meanwhile, there was a significant variation in case of TLR4 gene. As a pilot study, the present results revealed that identified SNPs in IL8 and TLR4 genes can be used as a genetic marker and predisposing factor for resistance/susceptibility to digital dermatitis in dairy cows. However, TLR4 gene may be a potential candidate for such disease.


Nutrition issues of military women.
Nutritional data were collected from 147 female soldiers in four surveys (two field and two dining hall studies) conducted by the US Army Research Institute of Environmental Medicine and Letterman Army Institute of Research. The 49 female soldiers observed in the field studies had suboptimal mean energy (1751 kcal), protein (52.3 g), calcium (620 mg), and iron (11.8 mg) intakes. In addition, 54 female soldiers in the dining hall studies also had lower than desirable mean iron (16.2 mg) intakes. These data suggest that nutritional problems encountered by military women are similar to those faced by their civilian counterparts, based on NHANES II and CSFII reports. Although the impact of sporadic low nutrient intakes during short 10-14-day field training exercises may be of little consequence, this may be significant when inadequate intakes occur routinely or for extended periods during military conflicts. Viable solutions to the nutritional problems of military women could include ration supplementation and nutrition education.


TEM image restoration from fast image streams.
Microscopy imaging experiments generate vast amounts of data, and there is a high demand for smart acquisition and analysis methods. This is especially true for transmission electron microscopy (TEM) where terabytes of data are produced if imaging a full sample at high resolution, and analysis can take several hours. One way to tackle this issue is to collect a continuous stream of low resolution images whilst moving the sample under the microscope, and thereafter use this data to find the parts of the sample deemed most valuable for high-resolution imaging. However, such image streams are degraded by both motion blur and noise. Building on deep learning based approaches developed for deblurring videos of natural scenes we explore the opportunities and limitations of deblurring and denoising images captured from a fast image stream collected by a TEM microscope. We start from existing neural network architectures and make adjustments of convolution blocks and loss functions to better fit TEM data. We present deblurring results on two real datasets of images of kidney tissue and a calibration grid. Both datasets consist of low quality images from a fast image stream captured by moving the sample under the microscope, and the corresponding high quality images of the same region, captured after stopping the movement at each position to let all motion settle. We also explore the generalizability and overfitting on real and synthetically generated data. The quality of the restored images, evaluated both quantitatively and visually, show that using deep learning for image restoration of TEM live image streams has great potential but also comes with some limitations.


The polymerization efficiency of a bulk-fill composite based on matrix-modification technology.
To evaluate the polymerization efficiency of a matrix-modified bulk-fill composite, and compare it to a conventional composite which has a similar filler system. The degree of conversion (DC%) and monomer elution were measured over different storage periods. Additionally, fillers' content was examined. Cylindrical specimens were prepared, in bulk and incrementally, from Filtek Bulk Fill (B) and Filtek Supreme XTE (S) composites using a Teflon mold, for each test (n = 6). Using attenuated total reflection method of Fourier transformation infrared spectroscopy, DC% was measured after 24 hours, 7 days, and 30 days. Using high-performance liquid chromatography, elution of hydroxyethyl methacrylate, triethylene glycol dimethacrylate, urethane dimethacrylate, and bisphenol-A glycidyl dimethacrylate was measured after 24 hours, 7 days and 30 days. Filler content was examined by scanning electron microscopy (SEM). Data were analyzed using 2-way mixed-model analysis of variance (α = 0.05). There was no significant difference in DC% over different storage periods between B-bulk and S-incremental. Higher monomer elution was detected significantly from S than B. The elution quantity and rate varied significantly over storage periods and between different monomers. SEM images showed differences in fillers' sizes and agglomeration between both materials. Matrix-modified bulk-fill composites could be packed and cured in bulk with polymerization efficiency similar to conventional composites.


Modulation of liposomal membrane fluidity by flavonoids and isoflavonoids.
The polyphenolic structures of flavonoids and isoflavonoids confer them with the ability to scavenge free radicals and to chelate transition metals, a basis for their potent antioxidant abilities. Another possible contributory mechanism toward their antioxidant activities is their ability to stabilize membranes by decreasing membrane fluidity. In this study, the effects of representative flavonoids, isoflavonoids, and their metabolites on membrane fluidity and their preferential localization in the membrane were investigated using large unilamellar vesicles (LUVs) as the membrane models. These results were compared with those of cholesterol and alpha-tocopherol. Changes in fluorescence anisotropy values for a series of n-(9-anthroyloxy) fatty acid probes (n = 6, 12, 16) upon addition of the test compounds were used to monitor alterations in membrane fluidity at graded depths in lipid bilayer. The results of the study suggest that the flavonoids and isoflavonoids, similar to cholesterol and alpha-tocopherol, partition into the hydrophobic core of the membrane and cause a dramatic decrease in lipid fluidity in this region of the membrane. Localization of flavonoids and isoflavonoids into the membrane interiors and their resulting restrictions on fluidity of membrane components could sterically hinder diffusion of free radicals and thereby decrease the kinetics of free radical reactions.


Iodine and brain development.
The development of the brain is critically dependent on an adequate supply of iodine. Iodine is an integral part of thyroid hormone, which acts on brain development by regulating the expression of target genes. The active thyroid hormone, T3, is generated in part in the thyroid gland, but about 80% of T3 in brain is formed locally from T4 deiodination mainly by the action of a specific iodothyronine deiodinase. This enzyme is highly expressed in astrocytes, which take up T4 from the blood and deliver T3 for neuronal use. In the target cells T3 binds to nuclear receptors which are transcription factors. The T3 receptors are expressed in the brain before fetal thyroid gland function and may be activated by maternal thyroid hormone during midgestation. Although a group of thyroid hormone target genes has been identified in recent years, many basic questions of thyroid hormone action in the brain remain to be elucidated.


Genetic structure and function of an early transcript of visna virus.
During the early step of the lytic cycle, visna provirus is first transcribed into two small multispliced mRNAs of 1.6 and 1.2 kilobases which may encode factors regulating the replication of visna virus (R. Vigne, V. Barban, G. Quérat, V. Mazarin, I. Gourdou, and N. Sauze, Virology 161:218-227, 1987). By cDNA cloning and nucleotide sequencing, we determined that the 1.2-kilobase mRNA is 1,174 nucleotides long without the 3'-polyadenylated tail and is composed of four exons, two of which originated from the 5' and 3' ends, respectively, of the env gene region. Two overlapping open reading frames are present in each of these two exons. They were translated in vitro and gave rise to three proteins, two of 19 and 17 kilodaltons, termed VEP1, and one of 16.5 kilodaltons, termed STM. Only the VEP1 proteins were recognized by a hyperimmune anti-visna virus serum of infected sheep. Transient-expression assays performed in eucaryotic cells demonstrated that the cDNA clone described here has a trans-acting effect on transcription of the visna virus genes.


Photosynthesis in Flaveria brownii A.M. Powell : A C(4)-Like C(3)-C(4) Intermediate.
Leaves of Flaveria brownii exhibited slightly higher amounts of oxygen inhibition of photosynthesis than the C(4) species, Flaveria trinervia, but considerably less than the C(3) species, Flaveria cronquistii. The photosynthetic responses to intercellular CO(2), light and leaf temperature were much more C(4)-like than C(3)-like, although 21% oxygen inhibited the photosynthetic rate, depending on conditions, up to 17% of the photosynthesis rate observed in 2% O(2). The quantum yield for CO(2) uptake in F. brownii was slightly higher than that for the C(4) species F. trinervia in 2% O(2), but not significantly different in 21% O(2). The quantum yield was inhibited 10% in the presence of 21% O(2) in F. brownii, yet no significant inhibition was observed in F. trinervia. An inhibition of 27% was observed for the quantum yield of F. cronquistii in the presence of 21% O(2). The photosynthetic response to very low intercellular CO(2) partial pressures exhibited a unique pattern in F. brownii, with a break in the linear slope observed at intercellular CO(2) partial pressure values between 15 and 20 mubar when analyzed in 21% O(2). No significant break was observed when analyzed in 2% O(2). When taken collectively, the gas-exchange results reported here are consistent with previous biochemical studies that report incomplete intercellular compartmentation of the C(3) and C(4) enzymes in this species, and suggest that F. brownii is an advanced, C(4)-like C(3)-C(4) intermediate.


Overnight visitor counts in Australia and their implications for population estimation.
"On the night of the 1996 Census, 5.4 per cent of the people counted in Australia were staying away from home (visitors), compared to 4.6 per cent in 1986. Queensland's share of the nation's visitors has risen since 1986, largely at the expense of Western Australia's. Queensland is now the most popular destination for interstate and overseas visitors, while New South Wales hosts a large proportion of intrastate visitors. But the overall picture is partly obscured because the Census missed around 100,000 overseas visitors."


Case of acquired haemophilia a in Southeast Asia following COVID-19 vaccine.
Acquired haemophilia A (AHA) is a rare bleeding disorder with high morbidity and mortality, but it is eminently treatable if diagnosis and treatment are prompt. We report a case of AHA in Southeast Asia following the administration of the Pfizer-BioNTech COVID-19 vaccine. A man in his 80s developed multiple bruises 2 weeks after his first dose of the COVID-19 vaccine. Diagnosis was delayed due to his cognitive impairment and low clinical suspicion. This led to a representation with worsening ecchymosis, a left thigh haematoma and symptomatic anaemia. Laboratory testing was notable for an isolated prolongation of the activated partial thromboplastin time, which remained uncorrected in the mixing test. Further testing confirmed the presence of factor VIII (FVIII) inhibitors and low FVIII titres of 6.7%. He responded to treatment with intravenous methylprednisolone and recombinant activated FVII. Screening for autoimmune diseases and malignancies was negative.


Expression and regulation of the rabbit uteroglobin gene in transgenic mice.
The rabbit uteroglobin (UG) gene, with varying lengths of 5' flanking sequence, was introduced into the mouse genome to investigate the DNA sequences required for tissue-specific expression and regulation by steroid hormones. The pattern of expression and steroid hormone regulation of the transgene was compared to the expression and regulation of the endogenous mouse UG-like gene. In the rabbit, UG is induced in the uterus by progesterone and is expressed constitutively in the lungs, where it is weakly regulated by glucocorticoids. Genomic DNA fragments containing the complete UG-coding sequence with 4.0 (UG4.0), 3.0 (UG3.0), 2.3 (UG2.3), or 0.6 (UG0.6) kilobases of 5' flanking sequence were used to establish lines of transgenic mice. Expression of UG mRNA was observed in the lungs of UG4.0 (2/4 lines), UG3.0 (4/4 lines), UG2.3 (1/2 lines), and UG0.6 (4/4 lines) mice. Uterine expression was observed in UG3.0 (3/4 lines), UG2.3 (1/2 lines), and UG0.6 (2/4 lines). In the lungs of UG3.0 and UG2.3 mice, RNA expression was stimulated by treatment with dexamethasone. In the one line of UG3.0 mice examined, UG was regulated by ovarian steroids in the uterus. The endogenous mouse UG-like gene showed the major site of expression to be in the lung. Unlike the transgene, the endogenous gene was more strongly stimulated by glucocorticoids. Thus, we conclude that the cis elements needed for pulmonary expression of UG are contained within the UG2.3 fragment used to generate transgenic mice, but that other elements are required for full glucocorticoid regulation. Also, the transgene did not show the full uterine expression observed in the rabbit, but regulation by the ovarian steroids was observed.


Nonlinear dynamics of topological solitons in DNA.
Dynamics of topological solitons describing open states in the DNA double helix are studied in the framework of a model that takes into account asymmetry of the helix. It is shown that three types of topological solitons can occur in the DNA double chain. Interaction between the solitons, their interactions with the chain inhomogeneities, and stability of the solitons with respect to thermal oscillations are investigated.


Liver environment and HCV replication affect human T-cell phenotype and expression of inhibitory receptors.
There is an unclear relationship between inhibitory receptor expression on T cells and their ability to control viral infections. Studies of human immune cells have been mostly limited to T cells from blood, which is often not the site of infection. We investigated the relationship between T-cell location, expression of inhibitory receptors, maturation, and viral control using blood and liver T cells from patients with hepatitis C virus (HCV) and other viral infections. We analyzed 36 liver samples from HCV antibody-positive patients (30 from patients with chronic HCV infection, 5 from patients with sustained virological responses to treatment, and 1 from a patient with spontaneous clearance) with 19 paired blood samples and 51 liver samples from HCV-negative patients with 17 paired blood samples. Intrahepatic and circulating lymphocytes were extracted; T-cell markers and inhibitory receptors were quantified for total and virus-specific T cells by flow cytometry. Levels of the markers PD-1 and 2B4 (but not CD160, TIM-3, or LAG-3) were increased on intrahepatic T cells from healthy and diseased liver tissues compared with T cells from blood. HCV-specific intrahepatic CD8(+) T cells from patients with chronic HCV infection were distinct in that they expressed TIM-3 along with PD-1 and 2B4. In comparison, HCV-specific CD8(+) T cells from patients with sustained virological responses and T cells that recognized cytomegalovirus lacked TIM-3 but expressed higher levels of LAG-3; these cells also had different memory phenotypes and proliferative capacity. T cells from liver express different inhibitory receptors than T cells from blood, independent of liver disease. HCV-specific and cytomegalovirus-specific CD8(+) T cells can be differentiated based on their expression of inhibitory receptors; these correlate with their memory phenotype and levels of proliferation and viral control.


Impulsivity and aggressive behavior in Roman high and low avoidance rats: baseline differences and adolescent social stress induced changes.
Adverse and stressful experiences during adolescence are often of a social nature. The social defeat model in rats is used as an animal model for bullying in humans. Usually large individual differences in response to social defeat are found. The personality type that is mostly affected and the underlying mechanisms are unknown. We used male rats of the Roman selection lines to test whether social defeat (between postnatal days 45 and 57) followed by social isolation has a different impact in animals with divergent levels of emotional reactivity and coping style. The level of offensive aggression, impulsivity and performance during frustrating non-reward (extinction) were used as measures for the adult coping style of animals. Impulsivity was measured by performance on an unpredictable operant conditioning schedule (variable interval-15, VI-15) for food reinforcement. This study demonstrates that the adult, baseline level of impulsivity is higher in Roman high avoidance (RHA) rats. RHA rats showed a higher number of lever presses compared to Roman low avoidance (RLA) rats on a VI-15 schedule. The level of offensive aggression did not differ between the two lines. Surprisingly, a tendency towards more offensive aggression in RLA rats was found. Social stress during adolescence disturbed the normal development of adult personality, mostly in RHA rats. RHA rats that were defeated during adolescence reduced the number of lever presses on the VI-15 schedule of reinforcement and were more persistent during a session of frustrating non-reward. However, we did not find an effect of social defeat on performance during extinction. A tendency towards increased attack latencies after social defeat in adolescence was found. The time spent on offensive aggression was unaffected by social defeat.


BDNF-TrkB signaling interacts with the GABAergic system to inhibit rhythmic swallowing in the rat.
Brain-derived neurotrophic factor (BDNF) acts as an anorexigenic factor in the dorsal vagal complex (DVC) of the adult rat brain stem. The DVC contains the premotoneurons controlling swallowing, a motor component of feeding behavior. Although rats with transected midbrain do not seek out food, they are able to swallow and to ingest food. Because BDNF and tropomyosin-related kinase B (TrkB) receptors are expressed in the DVC, this study hypothesized that BDNF could modify the activity of premotoneurons involved in swallowing. Repetitive electrical stimulation of the superior laryngeal nerve (SLN) induces rhythmic swallowing that can be recorded with electromyographic electrodes inserted in sublingual muscles. We show that a microinjection of BDNF in the swallowing network induced a rapid, transient, and dose-dependant inhibition of rhythmic swallowing. This BDNF effect appeared to be mediated via TrkB activation, since it no longer occurred when TrkB receptors were antagonized by K-252a. Interestingly, swallowing was inhibited when subthreshold doses of BDNF and GABA were coinjected, suggesting a synergistic interaction between these two signaling substances. Moreover, BDNF no longer had an inhibitory effect on swallowing when coinjected with bicuculline, a GABA(A) receptor antagonist. This blockade of BDNF inhibitory effect on swallowing was reversible, since it reappeared when BDNF was injected 15 min after bicuculline. Finally, we show that stimulation of SLN induced a decrease in BDNF protein within the DVC. Together, our results strongly suggest that BDNF inhibits swallowing via modulation of the GABAergic signaling within the central pattern generator of swallowing.


Ubiquitin-Specific Peptidase 10 Protects Against Hepatic Ischaemic/Reperfusion Injury via TAK1 Signalling.
Ubiquitin-specific peptidase 10 (USP10) protein is a deubiquitination enzyme involved in many important biological processes. However, the function of USP10 in hepatic ischaemic/reperfusion (I/R) injury remains unknown. The aim of this study was to explore the role of USP10 in hepatic I/R injury. USP10 Heterozygote mice and primary hepatocytes were used to construct hepatic I/R models. The effect of USP10 on hepatic I/R injury was examined via pathological and molecular analyses. Our results indicated that USP10 was significantly downregulated in the livers of mice after hepatic I/R injury and in hepatocytes subjected to hypoxia/reoxygenation stimulation. USP10 Heterozygote mice exhibited exacerbated hepatic I/R injury, as evidenced by enhanced liver inflammation via the NF-κB signalling pathway and increased hepatocyte apoptosis. Additionally, USP10 overexpression inhibited hepatocyte inflammation and apoptosis in hepatic I/R injury in vitro and in vivo. Mechanistically, our study demonstrated that USP10 knockdown exerted its detrimental effects on hepatic I/R injury by inducing activation of the transforming growth factor β-activated kinase 1 (TAK1)-JNK/p38 signalling pathways. TAK1 was required for USP10 function in hepatic I/R injury as TAK1 inhibition abolished USP10 function in vitro. In conclusion, our study demonstrated that USP10 plays a protective role in hepatic I/R injury by inhibiting the activation of the TAK1-JNK/p38 signalling pathways. Modulation of USP10/TAK1 might be a promising strategy to prevent this pathological process.


Comparison of small mammal prevalence of Leishmania (Leishmania) mexicana in five foci of cutaneous leishmaniasis in the State of Campeche, Mexico.
In the Yucatan Peninsula of Mexico, 95% of the human cases of Cutaneous Leishmaniasis are caused by Leishmania (Leishmania) mexicana with an incidence rate of 5.08 per 100,000 inhabitants. Transmission is limited to the winter months (November to March). One study on wild rodents has incriminated Ototylomys phyllotis and Peromyscus yucatanicus as primary reservoirs of L. (L.) mexicana in the focus of La Libertad, Campeche. In the present study, the prevalence of both infection and disease caused by L. (L.) mexicana in small terrestrial mammals were documented during five transmission seasons (1994-2004) in five foci of Leishmaniasis in the state of Campeche. Foci separated by only 100 km, with similar relative abundances of small mammals, were found to differ significantly in their prevalence of both symptoms and infection. Transmission rates and reservoir species seemed to change in space as well as in time which limited the implementation of effective control measures of the disease even in a small endemic area such as the south of the Yucatan Peninsula.


Biodiversity of Anabaena azollae isolates from different Azolla cultures.
The random amplified polymorphic DNA (RAPD) profile of A. azollae strains isolated from four different Azolla cultures was studied by using different primers. The objective of this study was to determine whether polymerase chain reaction (PCR) with different primers could differentiate the isolated A. azollae strains from one another. The primers amplified specific sequences of the isolates and generated fingerprinting pattern characteristic of each isolate. Clear polymorphism was noticed among all the strains which depends on the primer sequence.


The initial 96 hours of invasive pulmonary aspergillosis: histopathology, comparative kinetics of galactomannan and (1->3) β-d-glucan and consequences of delayed antifungal therapy.
Acute invasive pulmonary aspergillosis is a rapidly progressive and frequently lethal infection. Relatively little is known about early events in the pathogenesis and relationship between the cell wall biomarkers galactomannan and (1→3)-β-d-glucan. The consequences of delayed antifungal therapy are also poorly defined. A persistently neutropenic rabbit model of invasive pulmonary aspergillosis was used to describe the histopathology of early invasive pulmonary aspergillosis and the kinetics of galactomannan and (1→3)-β-d-glucan. The time course of both molecules was mathematically modeled by using a population methodology, and Monte Carlo simulations were performed. The effect of progressive delay in the administration of amphotericin B deoxycholate 1 mg/kg at 24, 48, 72, and 96 h postinoculation on fungal burden, lung weight, pulmonary infarct score, and survival was determined. Histopathology showed phagocytosis of conidia by pulmonary alveolar macrophages at 4 h postinoculation. At 12 to 24 h, there was a progressive focal inflammatory response with conidial germination and hyphal extension. Subsequently, hyphae invaded into the contiguous lung. Galactomannan and (1→3)-β-d-glucan had similar trajectories, and both exhibited considerable interindividual variability, which was reflected in Monte Carlo simulations. Concentrations of both molecules began to rise <24 h postinoculation before pulmonary hemorrhagic infarction was present. Delays of 72 and 96 h in the administration of amphotericin B resulted in fungal burdens and lung weights that were indistinguishable from those of controls, respectively. Galactomannan and (1→3)-β-d-glucan have similar kinetics and are comparable biomarkers of early invasive pulmonary aspergillosis. Antifungal treatment at ≥48 h postinoculation is associated with suboptimal therapeutic outcomes.


Identifying victims of peer aggression from early to middle childhood: analysis of cross-informant data for concordance, estimation of relational adjustment, prevalence of victimization, and characteristics of identified victims.
Two studies were conducted to investigate cross-informant measures of children's peer victimization. In Study 1, self- and peer reports of victimization were compared for 197 children from Kindergarten (M age = 5.73) to Grade 4. Before Grade 2, peer reports were less reliable than self-reports and were poor estimators of relational adjustment. In Study 2, single- versus multiple-informant (self, peer, teacher, parent) victimization measures were compared for 392 children across grades 2 (M age = 8.73) to 4. Results indicated that (a) data from the four informants were reliable and increasingly concordant over time, (b) no single-informant measure proved to be the best predictor of relational adjustment, and (c) a multi-informant composite measure yielded better estimates of relational adjustment than any single-informant measure.


Caregivers' perceptions of informal social control practices to reduce child neglect: A qualitative study in Ghana.
Rational choice deterrence theory suggests that caregiving behavior, which includes abusive and neglectful behavior, can be influenced or manipulated via informal social control strategies enacted by neighbors, family members and friends in the social network. The literature identifies two forms of informal social control that have the potential to influence maltreating caregiver behavior, protective vs punitive, with the latter having more contrasting evidence related to its influence on maltreating caregiving practices. To examine the perceptions and meanings female caregivers associate with protective and punitive informal social control strategies that have been enacted against them. 17 female caregivers from Ghana, who self-reported their involvement in neglectful acts, were purposively selected to engage in river of life oral history narrative interviews. Narrative accounts from the caregivers were analyzed thematically using Taguette software package. The findings showed that protective informal social control in child neglect are interpreted via values and norms of childcare that have been institutionalized in the community. Caregivers perceived protective informal social control to have impact on their level of respect/influence, authority in the family or community, and to elicit internal consequences: shame, guilty feelings and embarrassment. Punitive informal social control approaches were considered as misplaced interventions that had ulterior motives of satisfying the neighbors' hatred/dislike of the perpetrator and quest for revenge. The findings suggest that the development of a fruitful theoretical framework to explain the effectiveness of informal social control should prioritize the social values and legitimate norms of the community. Implications for practice and theory development are discussed.


Diet change and exercise enhance protein expression of CREB, CRTC 2 and lipolitic enzymes in adipocytes of obese mice.
The study investigated the effects of regular exercise and diet changes on the change in metabolic processes of the cAMP-Response Element-Binding Protein-Regulated Transcription Coactivator (CRTC) family and its sub-lipolysis. Four-week-old C57/black male mice received an 8-week diet of general formula (control, CO; n = 10) or a high fat diet (HF; n = 30) to induce obesity. Thereafter, the mice received another 8-week regimen of general formula CO (n = 10) diet, continuous HF diet (n = 10), switched to general formula (diet change, DC; n = 10) or switched to general formula + exercise (diet and exercise, DE; n = 10). The DE group displayed significantly lower body weight, abdominal fat and lipid profiles (p < 0.05). The DE group also displayed significantly lower (35 %) CRTC 2 activity than the CO (p < 0.05). Activities of adipose triglyceride lipase (ATGL), hormone sensitive lipolitic enzyme (HSL) and monoacylglycerol lipase (MGL) were significantly higher (51 %, 38 %, 49 %) in the DE group than the HF group (p < 0.05). MGL, there were no differences between the CO group, HF group, and DC group, with the DE group (70 %) being significantly higher (p < 0.05). Change in diet in the absence of exercise was not associated with changes in adipose tissue CRTC family lipase activity, indicating that lipolysis metabolic processes are effective only when diet and exercise are carried out together.


[Comparison of clinical effect of two different Kirschner wire fixations after closed reduction on supracondylar fracture of humerus in children with GartlandⅡand Ⅲ].
To compare clinical effect of Kirschner wire radial sector fixation and bilateral ulnar radial cross fixation in treating supracondylar fracture of humerus in children after closed reduction. From March 2017 to December 2018, 60 children with supracondylar fracture of humerus treated with closed reduction and Kirschner wire fixation were analyzed retrospectively, and divided into two groups according to different needling methods. Thirty patients in radial three needles fan fixation group (group A), including 19 males and 11 females, aged from 2 to 10 years old with an average of (5.00±2.10) years old, 21 patients were typeⅡ and 9 patients were typeⅢ according to Gartland classification. Thirty patients in cross fixationwith 3 needles on both ulnar and radial side group(group B), including 22 males and 8 females, aged from 1 to 9 years old with an average of(5.13±2.08) years old, 19 patients were typeⅡand 11 patients were typeⅢ. Healing time of fracture, postoperative complications, elbow flexion and extension activity, forearm rotation activity recovery, elbow carrying angle and angle loss after operation between two groups were observed and compared. Mayo Elbow function score at the final following up was used to evaluate clinical efficacy. All patients were followed up, while there were no significant difference in follow-up time and fracture healing time between two groups (P>0.05);there was 1 patient occurred iatrogenic ulnar nerve injury in group A, 9 patients in group B, and there was difference between two groups (P<0.01);2 patients in group A occurred mild displacement and 1 patient in group B, while no significant difference between two groups(P>0.05). No cubitus varus deformity, needle infection, osteofascial compartment syndrome and myositis ossificans occurred. There was no significant difference in elbow flexion, extension activity, and forearm rotation activity between two groups at 3 months after operation(P>0.05); there was no significant difference in elbow carrying angle and its loss angle between two groups at 3 and 6 months after operation (P>0.05);there was also no significant difference in Mayo Elbow function score and efficacy evaluation at the final follow-up (P>0.05). Closed reduction and Kirschner wire at the early stage of fracture has advantages of less trauma, easy reduction, stable fixation, and early functional exercise. The risk of iatrogenic ulnar nerve injury caused by fan-shaped fixation of three radial needles is less than that of cross fixation of three radial needles.


Phospholipase-catalyzed hydrolysis in an artificial cell membrane in the presence of melittin.
Biomimicry involves the use of the structure and function of biological systems as models for the design and engineering of materials and machines. An artificial cell membrane was developed using biomembrane components, and the membrane, formed by a lipid bilayer, was analyzed using surface plasmon resonance (SPR) to monitor hydrolysis by phospholipase (PL). The simultaneous atomic force microscope (AFM) images show that PL catalyzed the nanometer-scale hydrolysis of the artificial lipid biomembranes through enzymatic hydrolysis. In addition, it was confirmed that the combination of PL and melittin allowed the control of enzyme hydrolysis for the degradation of the lipid bilayer. Regarding the expected activating effect of melittin on hydrolysis, no difference with respect to the non-treated lipid membrane was observed in the AFM images. It is assumed that the partitioning of melittin into the membrane might prevent the binding or hydrolysis of Phospholipase A2 (PLA2). This study provides basic knowledge on a new approach for patterning biomimicking lipid membranes on a nano-scale.


Pharmacological and pharmaceutical properties of freeze-dried formulations of egg albumin, indomethacin, olive oil, or fatty acids.
Formulations consisting of egg albumin, indomethacin (IND), and olive oil or fatty acids, were prepared by vigorous stirring using a high-speed homogenizer and subsequent freeze-drying. To confirm the anti-inflammatory properties and ulcerogenic effects of the formulations, we examined the action of the formulations on carrageenan-induced edema in rats as well as their ulcerogenic actions in the same species. Compared with IND alone, albumin-IND-olive oil (9:1:4.3), albumin-IND-linolenic acid (9:1:4.3), albumin-IND-linolic acid (9:1:4.3), albumin-IND-oleic acid (9:1:4.3), albumin-IND-stearic acid (9:1:4.3), and albumin-IND-tristearin (9:1:4.3) formulations all exhibited a more potent inhibitory effect on carrageenan-induced edema. In addition, the inhibitory effects on edema formation of an albumin-IND (9:1) complex was as strong as that of IND alone. These results suggested that the bioavailability of IND was increased by olive oil, fatty acid, and tristearin as absorbefacient agents. The increase in the bioavailability was evident from the fact that the mean plasma levels, maximum plasma levels (Cmax), and area under plasma concentration-time curve (AUC) values after oral administration of the albumin-IND-olive oil (9:1:4.3) formulation was significantly greater than that after administration of the drug alone. With respect to their ulcerogenic properties, the formulations were significantly less active than IND alone, suggesting that a reduction in the ulcerogenic activity of IND was by produced complexation with egg albumin.


Thermodynamic epimeric equilibration and crystallisation-induced dynamic resolution of lobelanine, norlobelanine and related analogues.
The step-economical synthesis of lobelanine involving a ring closing double aza-Michael (RCDAM) reaction is revisited and successfully extended to the synthesis of various configurationally more stable analogues. Owing to the presence of a configurationally labile β-aminoketone subunit, lobelanine is prone to self-catalyze mutarotation in solution. Through the synthesis of original lobelanine analogues, we studied the influence of (i) the size of the central heterocycle, (ii) the bulkiness of the nitrogen protecting group, and (iii) the phenacyl arm substituent on the thermodynamic equilibrium and its displacement by crystallisation-induced dynamic resolution (CIDR). We demonstrated that fine structural tuning combined with optimized CIDR conditions favours the first efficient diastereoselective synthesis of lobelanine's analogues.


[Correlation of limb and myocardial ischemia postconditioning with acute myocardial reperfusion injury].
We tested the hypothesis that remote postconditioning, which is induced by a single 5-min episode of femoral artery occlusion and reperfusion applied just before the onset of coronary artery reperfusion, protects the myocardium from reperfusion injury. In anesthetized open-chest rabbits, the left anterior descending artery (LAD) was occluded for 30 min and reperfused for 3 hrs. All rabbits were randomly divided into four groups (n = 10 in each group): (1) CONTROL: LAD occlusion and reperfusion only, with no other intervention; (2) Myocardial ischemic preconditioning (Pre-con): Three cycles of myocardial ischemia (5 min) and reperfusion (5 min) preceded the index ischemia/reperfusion protocol; (3) Myocardial ischemic postconditionng (Post-con): After 30 min of LAD occlusion, reperfusion was initiated for 30 s followed by 30 s reocclusion. Three cycles of myocardial ischemia (30 s) and reperfusion (30 s) followed the index ischemia/reperfusion protocol. (4) Remote postconditioning (Re Post-con): After 24 min of LAD occlusion, the femoral artery was occluded for 5 min and released for 1 min before 3 hrs of LAD reperfusion. Myocardial infarct size and tissue myeloperoxidase (MPO) activity were determined at the end of the experiment. Plasma creatine kinase (CK) activity and malondialdehyde (MDA) activity were measured at baseline, the end of ischemia, and after 3 hrs of reperfusion respectively. Myocardial infarct size was significantly reduced in Pre-con (15.5% +/- 1.7%, P < 0.01), Post-con (16.15% +/- 2.05%, P < 0.01) and Re Post-con (17.11% +/- 1.70%, P < 0.01) groups as compared to CONTROL (31.46% +/- 1.28%). Results were confirmed by plasma CK activity (in Re Post-con 18.0 IU/g +/- 1.6 IU/g vs. CONTROL 45.6 IU/g +/- 5.5 IU/g). Plasma MDA was significantly less at 3 hrs of reperfusion in Pre-con (2.12 micromol/ml +/- 0.30 micromol/ml, P < 0.01), Post-con (2.17 micromol/ml +/- 0.24 micromol/ml, P < 0.01) and Re Post-con (2.16 micromol/ml +/- 0.33 micromol/ml, P < 0.01) than that in CONTROL (3.49 micromol/ml +/- 0.32 micromol/ml). Neutrophil accumulation (MPO activity) in the area at risk was less in Pre-con (1.43 U/100 g +/- 0.32 U/100 g, P < 0.01), Post-con (2.26 U/100 g +/- 0.28 U/100 g, P < 0.01) and Re Post-con (2.45 U/100 g +/- 0.28 U/100 g, P < 0.01) than that in CONTROL (5.44 U/100 g +/- 0.46 U/100 g). Remote limb postconditioing applied just before the onset of coronary artery reperfusion provides potent myocardial infarct size reduction, which is similar to the cardioprotective effect of myocardial postconditioning exerted during the first minutes of coronary reperfusion. The potential mechanism of this inter-organ remote postconditioning phenomenon might be associated with decreasing the injury caused by oxygen free radicals and strengthening the action of antioxidation.


Construction of a High-Density Genetic Map Based on SLAF Markers and QTL Analysis of Leaf Size in Rice.
Leaf shape is an important agronomic trait for constructing an ideal plant type in rice, and high-density genetic map is facilitative in improving accuracy and efficiency for quantitative trait loci (QTL) analysis of leaf trait. In this study, a high-density genetic map contained 10,760 specific length amplified fragment sequencing (SLAF) markers was established based on 149 recombinant inbred lines (RILs) derived from the cross between Rekuangeng (RKG) and Taizhong1 (TN1), which exhibited 1,613.59 cM map distance with an average interval of 0.17 cM. A total of 24 QTLs were detected and explained the phenotypic variance ranged from 9% to 33.8% related to the leaf morphology across two areas. Among them, one uncloned major QTL qTLLW1 (qTLL1 and qTLLW1) involved in regulating leaf length and leaf width with max 33.8% and 22.5% phenotypic variance respectively was located on chromosome 1, and another major locus qTLW4 affecting leaf width accounted for max 25.3% phenotypic variance was mapped on chromosome 4. Fine mapping and qRT-PCR expression analysis indicated that qTLW4 may be allelic to NAL1 (Narrow leaf 1) gene.


Virtual Screening Techniques to Probe the Antimalarial Activity of some Traditionally Used Phytochemicals.
Malaria parasites show resistance to most of the antimalarial drugs and hence developing antimalarials which can act on multitargets rather than a single target will be a promising strategy of drug design. Here we report a new approach by which virtual screening of 292 unique phytochemicals present in 72 traditionally important herbs is used for finding out inhibitors of plasmepsin-2 and falcipain-2 for antimalarial activity against P. falciparum. Initial screenings of the selected molecules by Random Forest algorithm model of Weka using the bioassay datasets AID 504850 and AID 2302 screened 120 out of the total 292 phytochemicals to be active against the targets. Toxtree scan cautioned 21 compounds to be either carcinogenic or mutagenic and were thus removed for further analysis. Out of the remaining 99 compounds, only 46 compounds offered drug-likeness as per the 'rule of five' criteria. Out of ten antimalarial drug targets, only two target proteins such as 3BPF and 3PNR of falcipain-2 and 1PFZ and 2BJU of plasmepsin-2 are selected as targets. The potential binding of the selected 46 compounds to the active sites of these four targets was analyzed using MOE software. The docked conformations and the interactions with the binding pocket residues of the target proteins were understood by 'Ligplot' analysis. It has been found that 8 compounds are dual inhibitors of falcipain-2 and plasmepsin-2, with the best binding energies. Compound 117 (6aR, 12aS)-12a-Hydroxy-9-methoxy-2,3-dimethylenedioxy-8-prenylrotenone (Usaratenoid C) present in the plant Millettia usaramensis showed maximum molecular docking score.


Unilateral Masugi nephritis in the rat.
In unilateral nephritis produced in rats by clamping one kidney, injecting heterologous Masugi antiserum prepared from homogenates of cortex, and releasing the clamp after 30 to 60 minutes, nephritis develops in the unclamped kidney. In the clamped kidney, although nephritis does not occur, the injected heterologous antibody can be demonstrated in the glomeruli with immunofluorescence techniques, and the intensity increases with time. Antirat glomerular basement membrane antisera and antirat tubular fraction 3 antisera were raised separately in rabbits. Rats with one kidney pedicle clamped were injected with antirat raised separately in rabbits. Rats with one kidney pedicle clamped were injected with antirat glomerular basement membrane antiserum alone, antirat tubular fraction 3 alone, or a mixture of both. The clamp was released after 1 hour. Frozen sections of the kidney were stained at intervals for the presence of rabbit IgG and rat IgG. When antirat glomerular basement membrane was injected alone, faint linear fluorescence was noted at 24 hours in the clamped kidney, and this did not increase over 4 weeks. Antirat tubular fraction 3 antiserum injected alone showed fine granular deposits around the capillary walls at 24 hours, and the intensity of fluorescence increased with time. When a mixture of antirat glomerular basement membrane and antirat tubular fraction 3 was injected, in the clamped kidney, there was initially faint linear fluorescence. By the 8th day, a granular pattern was noted superimposed on a linear background. By 32 days, the granular pattern was evident. The presence of subepithelial deposits was confirmed by electron microscopy. It is deduced that the slow reacting factor in Masugi antiserum prepared from homogenates of cortex is partly a "contaminating" antitubular antibody and that injections of Masugi antiserum may produce two superimposed types of immunologic glomerular lesions.


Evaluation of triggers for corneal graft rejection.
To evaluate potential triggering factors contributing to corneal graft rejection. A prospective, case control study was conducted over a five month period. All patients presenting with new onset corneal graft rejection were enrolled into the study group. Two patients with clear grafts who presented shortly after each enrolled study group patient served as controls. Groups were matched for age, preoperative diagnosis, and number of previous keratoplasties. Participating patients and examining ophthalmologists filled out questionnaires regarding infectious, environmental and immunologic exposures. 66 patients were enrolled into the study, of which 22 had new rejection episodes. The most prevalent diagnoses were keratoconus (36.6%) and herpes simplex keratitis (22.7%). Anterior chamber reaction (77.3%) and keratic precipitates (68.2%) were the most common signs of graft rejection. A history of prior rejection episodes was significantly more frequent in the study group population (p < 0.001). Factors such as sun exposure, stress, smoking and travel were more prevalent in the rejection group but not statistically significant. The history of recent vaccinations and allergic reactions were equally prevalent in both groups. The new onset of corneal graft rejection was highly associated with a prior history of graft rejection episodes (p < 0.001). Other analyzed factors were not significant triggering factors for rejection in this small series.


Compensation for attenuation, scatter, and detector response in SPECT reconstruction via iterative FBP methods.
Iterative filtered backprojection (FBP) reconstruction is a fast method for single photon emission computed tomography (SPECT) that can provide simultaneous compensation for nonuniform attenuation, scatter, and distance-dependent detector response. The iterative FBP method was applied to the reconstruction of SPECT images of a chest phantom consisting of nonuniform attenuating media. One hundred twenty projections containing 20 million counts were reconstructed on an image array of 128 x 128 x 64. The accuracy of reconstruction was significantly improved, in terms of concentration ratio, object shape, and noise reduction. Results of this experimental study indicate that interactive FBP can effectively reconstruct SPECT images, while other iterative methods, such as maximum a posteriori probability (MAP), will spend at least ten times more computing effort in the reconstruction on the same computer. The disadvantage of iterative FBP is its inability to model the noise properties of data collection accurately, as compared to the MAP methods.


Plant Bioactives and the Prevention of Prostate Cancer: Evidence from Human Studies.
Prostate cancer has become the most common form of non-cutaneous (internal) malignancy in men, accounting for 26% of all new male visceral cancer cases in the UK. The aetiology and pathogenesis of prostate cancer are not understood, but given the age-adjusted geographical variations in prostate cancer incidence quoted in epidemiological studies, there is increasing interest in nutrition as a relevant factor. In particular, foods rich in phytochemicals have been proposed to reduce the risk of prostate cancer. Epidemiological studies have reported evidence that plant-based foods including cruciferous vegetables, garlic, tomatoes, pomegranate and green tea are associated with a significant reduction in the progression of prostate cancer. However, while there is well-documented mechanistic evidence at a cellular level of the manner by which individual dietary components may reduce the risk of prostate cancer or its progression, evidence from intervention studies is limited. Moreover, clinical trials investigating the link between the dietary bioactives found in these foods and prostate cancer have reported varied conclusions. Herein, we review the plant bioactives for which there is substantial evidence from epidemiological and human intervention studies. The aim of this review is to provide important insights into how particular plant bioactives (e.g., sulphur-containing compounds, carotenoids and polyphenols) present in commonly consumed food groups may influence the development and progression of prostate cancer.


Electropharmacograms of rasagiline, its metabolite aminoindan and selegiline in the freely moving rat.
Rasagiline and selegiline are classified as monoamine oxidase B (MAO-B) inhibitors. The present investigation deals with time-dependent electrical frequency changes (electropharmacograms) induced by these, as well as by aminoindan, the major metabolite of rasagiline. Adult rats (day-night converted, >5 months old) were fitted with 4 bipolar concentric steel electrodes connected to a small base plate, which was positioned stereotactically for insertion of the electrodes into the frontal cortex, hippocampus, striatum and reticular formation. The plate carried a small plug to receive a telemetric device during the experimental session. Changes in field potentials were recorded during a pre-drug reference period of 45 min, followed by intraperitoneal administration and 5 h of recording thereafter. Data were transmitted wirelessly for frequency analysis. Data from 10 animals treated within a crossover design were averaged. A dose of 0.25 mg/kg i.p. rasagiline produced statistically significant decreases in spectral alpha2 and beta1 power. Higher dosages showed a linear enhancement of this effect. A similar pattern was obtained after administration of aminoindan (2-10 mg/kg), but of shorter duration. Selegiline produced a similar pattern only for the first 1-2 h. After this, statistically significant increases in delta and theta power were observed. Despite the feature of MAO-B inhibition in both drugs and its reflection in the initial changes of the frequency pattern during the first hour, the pharmacological action of selegiline during the following hours differs profoundly from that of rasagiline, presumably due to the toxicity of its major metabolites methamphetamine and amphetamine.


Using silver nanoparticle and thiol graphene quantum dots nanocomposite as a substratum to load antibody for detection of hepatitis C virus core antigen: Electrochemical oxidation of riboflavin was used as redox probe.
In this study a facile green approach to employ silver nanoparticle (AgNPs) and thiol graphene quantum dots (GQD-SH) as the nanomaterial for ultrasensitive and selective detection of hepatitis C virus core antigen (HCV) have been investigated. AgNPs/GQD-SH was utilized as a substratum to load antibody for detection of hepatitis C virus core antigen. AgNPs have been immobilized on SH groups of GQDs via bonding formation of Ag-S and anti-HCV have been loaded on the electrode surface via the interaction between -NH2 group of antibody and AgNPs. Using the proposed nanocomposite provides a specific platform with increased surface which is capable of loading more antibodies to entrap the antigen. The decreasing of the electrochemical signal can be achieved after the specific recognition between antibodies and antigens. Riboflavin was used as a biological molecule with inherent properties, for the first time, as the redox probe in the development of HCV core antigen electrochemical immunosensor. Compared to the other redox probes, riboflavin is superior in its oxidization in negative potential range, where the number of interfering species for riboflavin is much fewer. The proposed immunosensor showed wide linear range from 0.05pgmL-1 to 60ngmL-1 with limit of detection of 3fgmL-1. This novel immunosensor was used to analyze the serum sample. The immunosensor provides a convenient, low-cost and simple method for HCV core antigen detection and proposes new horizons for quantitative detection of antigen in the clinical diagnosis.