Zone specific trends in coral cover, genera and growth-forms in the World-Heritage listed Ningaloo Reef.
On coral reefs, changes in the cover and relative abundance of hard coral taxa often follow disturbance. Although the ecological responses of common coral taxa have been well documented, little is known about the ecological responses of uncommon coral taxa or of coral morphological groups across multiple adjacent reef zones. We used Multivariate Auto-Regressive State-Space modelling to assess the rate and direction of change of hard coral cover across a variety of coral genera, growth forms, and susceptibility to bleaching and physical damage covering multiple reef zones at northern Ningaloo Reef in Western Australia. Trends were assessed between 2007 and 2016, during which multiple episodic disturbances occurred including cyclones and a heatwave. We provide evidence of zone specific trends, not only in total hard coral cover, but also in taxonomic and morphological groups of corals at Ningaloo Reef. Declines in total coral cover on the reef flat corresponded with declines in fast growing corals, particularly Acropora. In contrast, total coral cover on the reef slope and inshore (lagoon) did not undergo significant change, despite divergent trajectories of individual genera. Importantly, we also show that changes in the composition of coral assemblages can be detected using a morphological based approach when changes are not evident using a taxonomic approach. Therefore, we recommend that future assessments of coral reef trends incorporate not just standard metrics such as total coral cover, but also metrics that provide for detailed descriptions of trends in common and uncommon taxa and morphological groups across multiple reef zones.


Single-lumen subcutaneous ports inserted by interventional radiologists in patients undergoing chemotherapy: incidence of infection and outcome of attempted catheter salvage.
Subcutaneous ports are commonly used for vascular access in patients with cancer undergoing chemotherapy. To determine the incidence of catheter-related infection and to assess the efficacy of catheter salvage in subcutaneous ports. We retrospectively reviewed 300 subcutaneous single-lumen chest ports inserted by interventional radiologists in 294 patients between December 1, 1995, and November 15, 1997, at the Cleveland Clinic Foundation, Cleveland, Ohio. The number of days that the catheter remained in situ, infection rate, treatment, and outcome of infection were determined. Two hundred ninety-four patients had a total of 79 748 catheter-days. Vascular access for chemotherapy was the indication for 95% of the subcutaneous ports placed. Seventeen catheters (5.7%) developed 20 episodes of noninfectious complications resulting in the removal of 6 ports. Seventeen patients (5.7%) developed catheter-related infections (2.1/10 000 catheter-days) including 10 episodes of catheter-related bacteremia (1.2/10 000 catheter-days). The most common organism isolated was Staphylococcus aureus. A total of 15 of the 17 infected catheters were removed. Salvage was attempted in 6 patients in whom 4 catheters were eventually removed due to recurrent bacteremia (2 patients) and persistent local infection (2 patients). One of the 10 patients with catheter-related bacteremia developed septic arthritis. There were no complications associated with attempted catheter salvage. Subcutaneous single-lumen ports inserted by interventional radiologists in patients undergoing chemotherapy have low complication rates but infections remain the leading cause of catheter loss. Antibiotic therapy without catheter removal is unlikely to eradicate catheter-related bacteremia.


Screening crystallisation conditions using fluorescence correlation spectroscopy.
We investigate the potential of fluorescence correlation spectroscopy (FCS) in screening for crystallisation conditions. Solutions that nucleate protein crystals must have different interactions than solutions that do not give rise to crystals. Due to these different interactions the average mean squared displacement of the individual proteins changes. By monitoring protein self-diffusion, we can distinguish crystallizing from non-crystallizing solutions. The method introduced can be applied at extremely low concentrations in femtoliter volumes as an early diagnostic for molecular association. Based on our preliminary findings FCS has the potential to become a routine screening method for crystallography.


Sleep apnea phenotyping and relationship to disease in a large clinical biobank.
Sleep apnea is associated with a broad range of pathophysiology. While electronic health record (EHR) information has the potential for revealing relationships between sleep apnea and associated risk factors and outcomes, practical challenges hinder its use. Our objectives were to develop a sleep apnea phenotyping algorithm that improves the precision of EHR case/control information using natural language processing (NLP); identify novel associations between sleep apnea and comorbidities in a large clinical biobank; and investigate the relationship between polysomnography statistics and comorbid disease using NLP phenotyping. We performed clinical chart reviews on 300 participants putatively diagnosed with sleep apnea and applied International Classification of Sleep Disorders criteria to classify true cases and noncases. We evaluated 2 NLP and diagnosis code-only methods for their abilities to maximize phenotyping precision. The lead algorithm was used to identify incident and cross-sectional associations between sleep apnea and common comorbidities using 4876 NLP-defined sleep apnea cases and 3× matched controls. The optimal NLP phenotyping strategy had improved model precision (≥0.943) compared to the use of one diagnosis code (≤0.733). Of the tested diseases, 170 disorders had significant incidence odds ratios (ORs) between cases and controls, 8 of which were confirmed using polysomnography (n = 4544), and 281 disorders had significant prevalence OR between sleep apnea cases versus controls, 41 of which were confirmed using polysomnography data. An NLP-informed algorithm can improve the accuracy of case-control sleep apnea ascertainment and thus improve the performance of phenome-wide, genetic, and other EHR analyses of a highly prevalent disorder.


Paclitaxel inhibits mRNA transport in axons.
Paclitaxel is an integral component of solid tumor treatment. This chemotherapeutic agent provokes an often irreversible peripheral sensory neuropathy with pathological features of distal axonal degeneration. Current pathological concepts assume that polymerization of axonal microtubules and mitochondrial dysfunction contributes to the development of paclitaxel-induced peripheral neuropathy. The relationship, however, between microtubule stabilization, mitotoxicity and axonal degeneration is still not completely understood. To explore the function of axonal mitochondria we treated transgenic mice that harbor cyan fluorescent protein (CFP)-labeled neuronal mitochondria with repeated doses of paclitaxel and assessed neuropathic changes by nerve conduction and histological studies. In addition, mitochondrial content and morphology was determined by ex vivo imaging of axons containing CFP-labeled mitochondria. Using quantitative RT-PCR and fluorescence-labeled mRNA we determined axonal mRNA transport of nuclear encoded mitochondrial proteins. Prolonged treatment with high doses of paclitaxel-induced a predominant sensory neuropathy in mice. Although mitochondrial velocity in axons per se was not altered, we observed significant changes in mitochondrial morphology, suggesting that paclitaxel treatment impairs the dynamics of axonal mitochondria. These changes were caused by decreased levels of nuclear encoded mRNA, including the mitochondrial fusion/fission machinery. Moreover, impaired axonal mRNA transport in vitro resulted in mitochondrial dysfunction and subsequent axonal degeneration. Taken together, our experiments provide evidence that disrupted axonal transport of nuclear derived mRNA plays a crucial role in the pathogenesis of paclitaxel-induced sensory neuropathy.


Changing patterns of autopsy findings among persons with acquired immunodeficiency syndrome in an inner-city population. A 12-year retrospective study.
To determine patterns of autopsy findings among persons with acquired immunodeficiency syndrome (AIDS) during a 12-year period. All 168 autopsies performed on adult AIDS patients at the Bronx-Lebanon Hospital Center in New York City between 1982 and 1993 were analyzed. The Center is a 725-bed, acute-care facility in the south Bronx, which serves a population of approximately half a million people. High poverty levels, tuberculosis and AIDS incidence, and intravenous drug abuse are common in this population. Subjects were predominantly Hispanic and black. Changes in the frequency of single and multiple opportunistic infections in general and frequencies of specific infections during the 12-year period. Through 1986, 75% of AIDS autopsies demonstrated single infections, particularly Pneumocystis carinii pneumonia. Since 1987, 72% of autopsies demonstrated multiple infections related to P carinii pneumonia, mycobacteriosis, cytomegalovirus, and various fungi. During the last 3 years, the prevalence of mycobacterial infections was higher than in the previous 9 years combined. In contrast, P carinii pneumonia decreased from 52% in 1988 to 14% in 1993. We note the recent emergence of multiple infections by multiple organisms, a significant decrease in the prevalence of P carinii pneumonia, and a slight increase in mycobacterial tuberculosis. Awareness of these changing patterns of infection may be useful in treating persons with AIDS.


Factors influencing recent dental graduates' location and sector of employment in Victoria.
Recruitment and retention of dentists in the public sector and rural areas in Victoria has become increasingly difficult in recent years. There are little available data on the factors that influence the sector and location of practice of new dental graduates. The objective of this study was to investigate the factors considered by new graduates in determining the location and sector of employment after graduation, and influencing any early changes in career path. Questionnaires were sent to dentists who Mgraduated from The Univrersity of Melbourne from graduated from The University of Melbourne from 2000-2003 who were currently practising in Victoria. There were 154 subjects to whom questionnaires were sent and 109 useable questionnaires were returned, a response rate of 74 per cent. Upon graduation, 53 per cent of the new graduates chose to work in the private sector only, compared to 15 per cent in public sector only and 33 per cent in both. At present, 71 per cent work in the private sector only, 17 per cent in the public sector only and 12 per cent in both. The most important factors for choosing to work in the private sector were receiving broad range of clinical experience, opportunities to familiarize with practice management and providing a continuity of care. The principal factors for practising in the public sector were clinical mentoring and advice, consolidating clinical skills and work environment. Initially, 48 per cent of the sample chose to work in metropolitan areas only, 39 per cent in rural areas only and 13 per cent in both. Factors that influenced the decision to work in rural areas were the broad range of clinical experience and remuneration, while the main factors for choosing to work in metropolitan areas were lifestyle and proximity to family and friends. This study found that a large proportion of new dental graduates initially chose to work in the public sector and rural areas on graduation primarily as a means of consolidating their clinical skills. However, retention of dentists in both these areas appears to be a problem, with less than 10 per cent of 2000-2001 graduates still than 10 per cent of 2000-2001 graduates still working in the public sector and only 20 per cent of 2000-2001 graduates still working in rural areas.


Aggressive osteoblastoma of the calcaneus.
Aggressive osteoblastoma of the left calcaneus in 29-year-old Japanese woman is reported. Her initial symptom was heel pain while walking. This was a primary calcaneal tumor, initially diagnosed as a benign osteoblastoma. After a 5-year follow-up (from the initial curettage), there was local recurrence. The histologic findings of aggressive osteoblastoma were confirmed after right lower leg amputation. The recurrent tumor was mildly aggressive to the talocalcanean joint and the retrocalcaneal area, without distant metastasis. The characteristics of the primary and recurrent tumors were examined by the radiologic, histologic, and electron microscopic procedures. Although there are questions about aggressive osteoblastoma, the authors believe that there are osteoblastic tumors of borderline malignancy between benign osteoblastoma and low-grade osteosarcoma. The current case was an example compatible with an aggressive osteoblastoma with the proposed name of Dorfman classification Group 4.


Neuroanatomical distribution of disease-associated prion protein in experimental bovine spongiform encephalopathy in cattle after intracerebral inoculation.
The pathologic disease-associated prion protein (PrP(Sc)) has been shown to be expressed in the central nervous system of Holstein cattle inoculated intracerebrally with 3 sources of classical bovine spongiform encephalopathy (BSE) isolates. Several regions of the brain and spinal cord were analyzed for PrP(Sc) expression by immunohistochemical and Western blotting analyses. Animals euthanized at 10 months post-inoculation (mpi) showed PrP(Sc) deposits in the brainstem and thalamus, but no vacuolation; this suggested that the BSE agent might exhibit area-dependent tropism in the brain. At 16 and 18 mpi, a small amount of vacuolation was detected in the brainstem and thalamus, but not in the cerebral cortices. At 20 to 24 mpi, when clinical symptoms were apparent, heavy PrP(Sc) deposits were evident throughout the brain and spinal cord. The mean time to the appearance of clinical symptoms was 19.7 mpi, and the mean survival time was 22.7 mpi. These findings show that PrP(Sc) accumulation was detected approximately 10 months before the clinical symptoms of BSE became apparent. In addition, the 3 sources of BSE prion induced no detectable differences in the clinical signs, incubation periods, neuroanatomical location of vacuoles, or distribution and pattern of PrP(Sc) depositions in the brain.


Synapsin I is a highly surface-active molecule.
Synapsin I is a neuron-specific phosphoprotein localized on the surface of small synaptic vesicles to which it binds with high affinity (Kd = 10 nM). Synapsin I exhibits a tendency to self-associate, suggesting that it might have amphiphilic properties. We have now found that synapsin I forms a stable monolayer at an air-water interface which can be compressed under a lateral force of up to 60 dynes/cm, indicating the presence of amphiphilic characteristics in its structure. This interpretation was also supported by circular dichroism spectra of synapsin I, which showed induction of secondary structure in the presence of trifluoroethanol. The various phosphorylated forms of synapsin I did not show any noticeable differences in the force-area isotherms. The monolayer properties of synapsin I fragments derived by cysteine-specific cleavage indicated the presence of amphiphilic characteristics throughout the entire sequence, although the C-terminal region showed less of such surfactant properties. Compositional studies of these fragments revealed that there is little interaction between the N-terminal and middle fragment regions, but that there may be some interaction between the C-terminal and middle fragment regions which affects the surface area occupied by these fragments. Based on this information, we propose a molecular topology for synapsin I consisting of amphiphilic regions and a hydrophilic region.


The therapeutic potential of RNA interference in controlling HIV-1 replication.
Human immunodeficiency virus type 1 (HIV-1) has long been a major problem to handle. Its existence is incurable (yet) and has reached pandemic proportions despite strictly-controlled epidemiological surveillance. The current treatment regimen involves the use of multiple antiretroviral agents (known as HAART) is very complex and may harm patients through its serious risk of toxicities. Moreover, the continuing emergence of drug resistance further threaten the future therapy, thereby necessitates another treatment strategy i.e. specific and efficient with low or minimal toxicity. RNAi is a potent candidate for the future treatment of HIV-1. It involves an immune-based silencing mechanism (post transcriptional gene silencing/PTGS) that uses small sequence of RNA (21-25 nucleotides in length) to inhibit almost every genes expression, including HIV-1 RNA and its mRNA byproducts. Since RNAi uses sequence of base pairs, it can be designed very specific and homologues to silence the genes in favor. RNAi works either through binding with HIV-1 to inhibit provirus integration into cellular genome or with mRNA products to inhibit certain genes expression (e.g. p24/Gag, Vif, Rev) that plays an important role in HIV-1 infectivity to knockdown its virulence capacity. Given the need for a treatment modality that are sequence-specific and able to overcome the highly mutation rate of virus like HIV-1, also by its enormous power to inhibit HIV-1 expression through various target sites, it is considered essential to discuss the molecular mechanism of RNAi, progresses that have been achieved, and future directions for its use in clinical settings.


Reactivation kinetics of acetylcholinesterase from different species inhibited by highly toxic organophosphates.
Standard treatment of poisoning by organophosphates (OP) includes the administration of an antimuscarinic agent, e.g. atropine, and of an acetylcholinesterase (AChE) reactivator (oxime). The presently available oximes, obidoxime and pralidoxime (2-PAM), are considered to be insufficient for highly toxic OPs, e.g. sarin. In the past decades numerous oximes were prepared and tested for their efficacy in OP poisoning, mostly in animal experiments. However, data indicate that the reactivating potency of oximes may be different in humans and animal species, which may hamper the extrapolation of animal data to humans and may pose a problem in the drug licensing of new compounds. In order to provide data for a better evaluation of the reactivating potency of oximes, experiments were undertaken to determine the reactivation rate constants of several oximes with human, rabbit, rat and guinea-pig AChE inhibited by the OPs sarin, cyclosarin and VX. The results show marked differences among the species, depending on the inhibitor and on the oxime, and indicate that the findings from animal experiments need careful evaluation before extrapolating these data to humans.


Developmental phytotoxicity of metal oxide nanoparticles to Arabidopsis thaliana.
Phytotoxicity is an important consideration to understand the potential environmental impacts of manufactured nanomaterials. Here, we report on the effects of four metal oxide nanoparticles, aluminum oxide (nAl(2)O(3)), silicon dioxide (nSiO(2)), magnetite (nFe(3)O(4)), and zinc oxide (nZnO), on the development of Arabidopsis thaliana (Mouse-ear cress). Three toxicity indicators (seed germination, root elongation, and number of leaves) were quantified following exposure to each nanoparticle at three concentrations: 400, 2,000, and 4,000 mg/L. Among these particles, nZnO was most phytotoxic, followed by nFe(3)O(4), nSiO(2), and nAl(2)O(3), which was not toxic. Consequently, nZnO was further studied to discern the importance of particle size and zinc dissolution as toxicity determinants. Soluble zinc concentrations in nanoparticle suspensions were 33-fold lower than the minimum inhibitory concentration of dissolved zinc salt (ZnCl(2)), indicating that zinc dissolution could not solely account for the observed toxicity. Inhibition of seed germination by ZnO depended on particle size, with nanoparticles exerting higher toxicity than larger (micron-sized) particles at equivalent concentrations. Overall, this study shows that direct exposure to nanoparticles significantly contributed to phytotoxicity and underscores the need for eco-responsible disposal of wastes and sludge containing metal oxide nanoparticles.


[Monolithic molecularly imprinted column-high performance liquid chromatography for enrichment and determination of trace cytokinins in plant samples].
A method based on monolithic molecularly imprinted polymer enrichment combining with high performance liquid chromatography (mMIP-HPLC) detection was developed for the selective determination of trace cytokinins (CTKs) in plant samples. Monolithic molecularly imprinted polymer (mMIP) column was prepared in stainless steel tube by using kinetin as the template, methacrylic acid (MAA) as the functional monomer, ethylene glycol dimethacrylate (EGDMA) as the cross-linker, and toluene-dodecanol as the porogenic solvents. Compared with non-imprinted polymer (NIP) monolith, the prepared mMIP exhibited selective separation ability, good reproducibility and reusability, and high extraction efficiency in the separation and enrichment of the four CTKs. Under the optimized experimental conditions, mean recoveries were 91.9%, 80.0%, 87.5% and 50.2% for kinetin (K), kinetin glucoside (KR) , trans-zeatin (tZ) and meta-topolin (mT), respectively, with the corresponding RSDs less than 11.8%. The proposed mMIP-HPLC method was successfully applied in the separation and determination of the four cytokinins in different plant samples


Is there a role for microsampling in antibiotic pharmacokinetic studies?
Clinical pharmacokinetic studies of antibiotics can establish evidence-based dosing regimens that improve the likelihood of eradicating the pathogen at the site of infection, reduce the potential for selection of resistant pathogens, and minimize harm to the patient. Innovations in small volume sampling (< 50 μL) or 'microsampling' may result in less-invasive sample collection, self-sampling and dried storage. Microsampling may open up opportunities in patient groups where sampling is challenging. The challenges for implementation of microsampling to assure suitability of the results, include: acceptable study design, regulatory agency acceptance, and meeting bioanalytical validation requirements. This manuscript covers various microsampling methods, including dried blood/plasma spots, volumetric absorptive microsampling, capillary microsampling, plasma preparation technologies and solid-phase microextraction. The available analytical technology is being underutilized due to a lack of bridging studies and validated bioanalytical methods. These deficiencies represent major impediments to the application of microsampling to antibiotic pharmacokinetic studies. A conceptual framework for the assessment of the suitability of microsampling in clinical pharmacokinetic studies of antibiotics is provided. This model establishes a 'contingency approach' with consideration of the antibiotic and the type and location of the patient, as well as the more prescriptive bioanalytical validation protocols.


Cytokinin signaling coordinates development of diverse organs in Marchantia polymorpha.
Cytokinins play an essential role in plant growth and development. A recent study showed that the cytokinin signaling pathway was conserved in the liverwort Marchantia polymorpha, and that it controlled gemma cup and rhizoid formation during thallus development. Here we show that the type-B response regulator, MpRRB, is mainly localized in the nucleus. Moreover, observations of thalli revealed that the distribution of air pores and the shape of the thallus margin are impaired in cytokinin-deficient lines and those defective in cytokinin signaling. This suggests that cytokinins regulate cell division and/or differentiation of precursor cells derived from the apical cell, thereby coordinating development of various organs produced on the thallus.


Effects of actinomycin D on fetal growth in rats.
The goal of this study was to determine the effects of actinomycin D on fetal growth and prostaglandin dehydrogenase activity and to determine whether these effects could be obtained by administering extracts of fetal calf serum (SS-094). Actinomycin D (7 microg/100 g body weight) was injected intraperitoneally on days 11 and 12 of pregnancy to induce growth restriction in rats. In another group, SS-094 was given (0.1 ml/100 g body weight) on days 12, 15, 17 and 19 of pregnancy, following the administration of actinomycin D. Placental prostaglandin dehydrogenase (PGDH) activity was measured on days 15 and 21 of pregnancy. Statistical analysis was performed by ANOVA and Dunnet's test. In the group injected with actinomycin D, fetal weight was significantly restricted (on day 15; p < 0.05; on day 21; p < 0.01), compared to the controls, and this restriction was successfully reversed by SS-094. PGDH activity in the placenta was significantly (p < 0.01) decreased in growth-restricted rats and remained low even after fetal weight recovered. Growth restriction in pregnant rats was successfully induced by actinomycin D, and SS-094 reversed this restriction. It does not seem that prostaglandin metabolism in the placenta is responsible for growth restriction.


Rub and Rinse Contact Lenses Before Wearing as a Protective Regimen Against Contact Lens-Related Eye Infections.
Data on contact lens (CL) users in Thailand are limited, and previous reports have mainly focused on young populations. This study aims to determine demographic data, hygienic behaviour, and complications related to the usage of CLs in the general population. This was a cross-sectional survey conducted from November 2020 to March 2021 using an anonymous questionnaire. Information on the demographic traits of the participants, characteristics of CL use, and CL care behaviours was collected. The responses were summarised and presented as a total behaviour score. Regression analysis was performed to evaluate the potential risk factors for a history of CL-related eye infections. A total of 134 CL wearers were recruited. Of all the participants, 83.58% were female and 16.42% were male. The average age was 31.14±10.69 years old. The total behaviour score showed that 62.69% of the population had good CL behaviour, while 37.31% exhibited poor CL behaviour. More than 50% of participants practised appropriate CL handling. Common unfavourable behaviours (>50%) reported were not using CL care solution to clean the storage case, not rubbing and rinsing the lens before storage, exposure to water during wear, use of makeup around the ocular area, and missing annual eye exams. Other less common but important instances of mishandling included using tap water to clean the lenses, topping off old CL solution, and exceeding the recommended planned-replacement period. However, no behaviours were significantly associated with a history of CL-related eye infections. Rubbing and rinsing CLs before wearing them was found to be a protective factor against a history of eye infections. Rubbing and rinsing CLs before wearing should be mentioned as an additional recommendation for the user.


The role of whole-body FDG PET/CT, Tc 99m MDP bone scintigraphy, and serum alkaline phosphatase in detecting bone metastasis in patients with newly diagnosed lung cancer.
Bone scan (BS) and serum alkaline phosphatase (ALP) concentration are used to detect bone metastasis in malignancy, although whole-body fluoro-D-glucose positron emission tomography computed tomography (FDG PET/CT) is being used increasingly. But BS is still used for the detection of metastatic bone lesion. So we compared the usefulness of PET/CT, BS, and serum ALP in detecting bone metastases in patients with newly diagnosed lung cancer. The medical record database was queried to identify all patients with a new diagnosis of lung cancer between January 2004 and December 2005, who had a PET/CT, BS, and serum ALP before treatment. We retrospectively reviewed all patients' records and radiological reports. One hundred eighty-two patients met the inclusion criteria. Bone metastases were confirmed in 30 patients. The sensitivity values were 93.3% for PET/CT, 93.3% for BS, 26.7% for serum ALP concentration, and 26.7% for BS complemented with serum ALP concentration. The respective specificity values were 94.1%, 44.1%, 94.1%, and 97.3%. The kappa statistic suggested a poor agreement among the three modalities. FDG PET/CT and BS had similar sensitivity, but PET/CT had better specificity and accuracy than BS. PET/CT is more useful than BS for evaluating bone metastasis. However, in the advanced stage, because of its high specificity, BS complemented with serum ALP is a cost-effective modality to avoid having to use PET/CT.


Oligomerization and regulation of higher plant phosphoenolpyruvate carboxylase.
The specific activity of phosphoenolpyruvate (PEP) measured at a saturating level of substrate diminishes as the enzyme is diluted at about the same rate that specific light scattering by the diluted enzyme decreases. The presence of PEP in the assay causes an increase in activity with increasing dilution. This is accompanied by an increase in light scattering of the diluted enzyme. The reverse situation obtains with the addition of malate to assays: the activity decreases with increasing dilution but light scattering is not substantially changed, indicating that the enzyme is already brought to a smaller aggregate by the dilution itself. In this case, the inhibition by malate in the assay probably is the noncompetitive type not involved in regulatory control by malate. Glucose-6-phosphate in the range from 1 to 6 millimolar causes an increase in activity of the enzyme run at a substrate level less than K(m), and an associated increase in light scattering is found, indicating an increase in the mean size of the enzyme. When PEP is added to a 1/80 diluted enzyme, light scattering increases and is associated with a more rapid activity of the enzyme. When malate is added to the same cuvette, the activity decreases and the light scattering diminishes, thus showing that the ligand response is immediately reversible. When malate is added first, followed by PEP, the reverse sequence of activity and light scattering change is observed.


Autologous haematopoietic stem cell transplantation compared with alemtuzumab for relapsing-remitting multiple sclerosis: an observational study.
To compare outcomes after treatment with autologous haematopoietic stem cell transplantation (AHSCT) and alemtuzumab (ALZ) in patients with relapsing-remitting multiple sclerosis. Patients treated with AHSCT (n=69) received a conditioning regimen of cyclophosphamide (200 mg/kg) and rabbit anti-thymocyte globulinerG (6.0 mg/kg). Patients treated with ALZ (n=75) received a dose of 60 mg over 5 days, a repeated dose of 36 mg over 3 days after 1 year and then as needed. Follow-up visits with assessment of the expanded disability status scale score, adverse events and MR investigations were made at least yearly. The Kaplan-Meier estimates of the primary outcome measure 'no evidence of disease activity' was 88% for AHSCT and 37% for ALZ at 3 years, p<0.0001. The secondary endpoint of annualised relapse rate was 0.04 for AHSCT and 0.1 for ALZ, p=0.03. At last follow-up, the proportions of patients who improved, were stable or worsened were 57%/41%/1% (AHSCT) and 45%/43%/12% (ALZ), p=0.06 Adverse events grade three or higher were present in 48/69 patients treated with AHSCT and 0/75 treated with ALZ in the first 100 days after treatment initiation. The most common long-term adverse event was thyroid disease with Kaplan-Meier estimates at 3 years of 21% for AHSCT and 46% for ALZ, p=0.005. In this observational cohort study, treatment with AHSCT was associated with a higher likelihood of maintaining 'no evidence of disease activity'. Adverse events were more frequent with AHSCT in the first 100 days, but thereafter more common in patients treated with ALZ.


CpG increases vaccine antigen-specific cell-mediated immunity when administered with hepatitis B vaccine in HIV infection.
Lack of adequate adjuvancy is a possible explanation for lack of vaccine immunogenecity. Immunostimulatory CpGs are potent vaccine adjuvants and may be an important component of the development vaccines, particularly those for which a cellular immune response is required for protection. We have previously demonstrated that CpG ODN co-administration with hepatitis B vaccine results in earlier, stronger and more sustained antibody responses to hepatitis B surface antigen in HIV infected individuals, and wished to determine if, in this population, helper T-cell responses were also enhanced. We conducted a double-blind, placebo-controlled trial in hepatitis B susceptible, effectively treated HIV-seropositive individuals. Participants received hepatitis B vaccine, with either placebo or CPG 7909 1.0 mg at week 0, 4 and 8. To determine the impact of CpG on cellular immune responses, lymphoproliferative responses (LPR) were evaluated by [3H]-thymidine incorporation at baseline and weeks 4, 8, 12, 24, and 48. Immunophenotyping of lymphocyte subsets was also determined at these time points. Of 36 patients enrolled, 18 received hepatitis B vaccine alone, and 18 received hepatitis B vaccine with CpG. Inclusion of CPG 7909 was associated with a greater proliferative response to HBsAg at all time points following initial vaccination. This increase was statistically significant at 8 weeks (p = 0.042) and 48 weeks (p = 0.024). Similar results were observed when LPR were evaluated as stimulation indices (SI). No differences in proliferative responses to HIV p24 Ag were observed, nor were there any differences in lymphocyte subsets. In addition to enhancing humoral responses to vaccination, we describe for the first time that CPG 7909 enhances cellular immunity to vaccine antigen in a typically hyporesponsive population. This adjuvancy may be important in the development of an effective vaccine for which a cellular immune response is required for protection.


Dissecting entropic coiling and poor solvent effects in protein collapse.
The early events in protein collapse and folding are guided by the protein's elasticity. The contributions of entropic coiling and poor solvent effects like hydrophobic forces to the elastic response of proteins are currently unknown. Using molecular simulations of stretched ubiquitin in comparison with models of proteins as entropic chains, we find a surprisingly high stiffness of the protein backbone, reflected by a persistence length of 1.2 nm, which is significantly reduced by hydrophobic forces acting between protein side chains to an apparent persistence length of 0.3-0.6 nm frequently observed in single-molecule stretching experiments. Thus, the poor solvent conditions of a protein in water lead to a protein compaction much beyond the coiling of an entropic chain and thereby allow a protein to appear softer than when using good solvents.


Excitatory synaptic transmission in neonatal dorsal horn: NMDA and ATP receptors.
Postnatal development sees a strong synaptogenesis in rat superficial dorsal horn. My studies show that synapses mediated by two excitatory neurotransmitters, glutamate and ATP, are functional since the very first postnatal days. Using an electrophysiological approach, the functional properties of two receptors activated by these neurotransmitters, glutamatergic NMDA and ATP ionotropic receptors, are described.


A patient survey on emergency department use of nurse practitioners.
The purpose of this descriptive study was to determine the willingness of emergency department patients, triaged to fast track areas, to be treated by an advanced practice registered nurse. A survey was distributed to a convenience sample of patients triaged to fast track areas in three southeastern emergency departments. The survey contained basic demographic information, four multiple-choice questions, and a section for comments. A majority of patients (65%) responded that they were willing to be treated by a nurse practitioner. Patients who had been treated by a nurse practitioner in the past were more willing to be treated by a nurse practitioner during this visit. The results of this study support the addition of nurse practitioners to fast track emergency department teams. Additional studies that focus on public and professional education regarding the role of the emergency nurse practitioner are warranted.


Association of Clinical Signs, Host Biomarkers and Etiology With Radiological Pneumonia in Bhutanese Children.
Diagnosing pneumonia and identifying those requiring antibiotherapy remain challenging. Chest radiographs (CXR) are often used as the reference standard. We aimed to describe clinical characteristics, host-response biomarkers and etiology, and assess their relationship to CXR findings in children with pneumonia in Thimphu, Bhutan. Children between 2 and 59 months hospitalized with WHO-defined pneumonia were prospectively enrolled and classified into radiological endpoint and non-endpoint pneumonia. Blood and nasopharyngeal washing were collected for microbiological analyses and plasma levels of 11 host-response biomarkers were measured. Among 149 children with readable CXR, 39 (26.2%) presented with endpoint pneumonia. Identification of respiratory viruses was common, with no significant differences by radiological outcomes. No clinical sign was suggestive of radiological pneumonia, but children with radiological pneumonia presented higher erythrocyte sedimentation rate, C-reactive protein and procalcitonin. Markers of endothelial and immune activation had little accuracy for the reliable identification of radiological pneumonia.


Urinary tract infections in children: renal ultrasound evaluation.
Ultrasound may replace urography in screening pediatric patients with uncomplicated urinary tract infections but without vesicoureteral reflux. A child undergoing a first radiographic evaluation for urinary tract infection is initially examined by voiding cystourethrography. If reflux is present, urography is performed. If no reflux is present, the kidneys are evaluated by real-time ultrasound; urography may also be performed if the ultrasound examination is abnormal, equivocal, or inadequate. A total of 192 patients was evaluated with this protocol; 146 (76%) had no reflux and therefore were examined with ultrasound. One patient was found to have hydronephrosis and underwent surgical correction. This group of patients was compared with a similar group of 223 patients without reflux who were evaluated by urography prior to the institution of the ultrasound protocol; there was no significant difference between the two groups in upper urinary tract findings that influenced patient management.


MicroRNA-300 inhibits the growth of hepatocellular carcinoma cells by downregulating CREPT/Wnt/β-catenin signaling.
A number of studies have demonstrated that altered expression levels of microRNA-300 (miR-300) are associated with tumor progression; however, little is understood regarding the role of miR-300 in hepatocellular carcinoma (HCC). The present study aimed to investigate the expression, biological function and potential regulatory mechanism of miR-300 in HCC. A miR-300 mimic and miR-300 inhibitor were transfected into liver cancer cells using RNAiMAX reagent. The expression levels of miR and mRNA were detected by reverse transcription-quantitative polymerase chain reaction. Protein expression levels were detected by western blot analysis. Cell growth was determined using Cell Counting Kit-8, a colony formation assay and cell cycle assay. miRNA targeting sites were analyzed using bioinformatics analysis and dual-luciferase reporter assay. The results revealed that miR-300 expression was significantly decreased in HCC tissues and cell lines. In vitro experiments demonstrated that overexpression of miR-300 could inhibit cell proliferation, colony formation and cell cycle progression of liver cancer cells. By contrast, inhibition of miR-300 was associated with increased rates of cell proliferation, colony formation and cell cycle progression. Notably, regulation of nuclear pre-mRNA domain-containing protein 1B (CREPT) was identified as a putative target gene of miR-300 by bioinformatics analysis. A luciferase reporter assay revealed that miR-300 directly targets the 3'-untranslated region of CREPT. Further data demonstrated that miR-300 can regulate CREPT expression levels in liver cancer cells. Notably, miR-300 was identified to regulate the Wnt/β-catenin signaling pathway in liver cancer cells. The restoration of CREPT expression partially reversed the antitumor effect of miR-300. In conclusion, the current results revealed a tumor suppressive role of miR-300 in HCC and indicated that the underlying mechanism was associated with a regulation of CREPT. The present study suggests that miR-300 and CREPT may serve as potential therapeutic targets for liver cancer.


Composition of the enterococcal and streptococcal intestinal flora of poultry.
Identification to species level showed that Enterococcus faecalis and Ent. faecium largely dominated the enterococcal and streptococcal gut flora of 1-d-old chicks. Enterococcus faecalis was rare in 3- to 5-week-old broilers. Two species, Ent. faecium and Streptococcus alactolyticus, were isolated from nearly all broilers examined. Enterococcus hirae and Ent. durans were found in the small intestines of this category of poultry. In layers and parent stock of over 12 weeks of age, Ent. cecorum dominated with Strep. alactolyticus ranking next. Other species were isolated irregularly. Enterococcus avium and Ent. gallinarum, originally described from chickens, were rarely found. These species did not appear to belong to the normal intestinal flora of poultry.


The Prevalence of Metabolic Syndrome and Different Obesity Phenotype in Iranian Male Military Personnel.
Obesity, especially when concentrated in the abdominal area, is often associated with the presence of metabolic syndrome. Stress, particularly occupational stress, is one of the most important factors contributing to the increased prevalence of metabolic syndrome components among different populations. This study aimed to investigate the prevalence of overweight and obesity as well as the criteria for metabolic syndrome and its risk factors and different obesity phenotype in a population of military personnel aged 20 to 65 years. This study is a retrospective cross-sectional study in which data are extracted from the database of a military hospital (2,200 participants). The records of participants contained information such as age, marital status, educational level, weight, height, body mass index, blood pressure, waist circumference, history of drug use and smoking, as well as the results of tests including lipid profile and fasting blood glucose. The Adult Treatment Panel III criteria as well as two national criteria were used to identify metabolic syndrome among participants. Data analysis was p1erformed using SPSS version 16. The average age of participants was 33.37 (7.75) years. The prevalence of metabolic syndrome according to Iranian cutoff was 26.6% for the waist circumference >90 cm (585 persons) and 19.6% for the waist circumference >95 cm (432 persons). The rate of metabolic syndrome was identified as 11.1% (432 cases) according to Adult Treatment Panel III criteria. Results of the current study identified that the prevalence of metabolic syndrome among military individuals is less than other populations, but the prevalence of the syndrome is higher than other military personnel in other countries.


Plasma cell balanitis presenting in a patient with a history of syphilis.
Plasma cell balanitis (PCB), also knows as Zoon balanitis, is a benign asymptomatic but chronic and erosive inflammatory condition of the glans penis and prepuce that generally affects uncircumcised men in later years. Clinical presentation involves a single, shiny, well defined reddish patch. We describe the first case of PCB ever reported in a patient with a previous history of syphilis, and include a review of the current literature. A 57-year-old Hispanic man with a remote history of syphilis presented with a 6-month nonhealing, granulating ulcer of the foreskin and glans penis that had been repeatedly mistaken for syphilis and treated unsuccessfully with circumcision 3 weeks previously. Biopsy of the glans penis demonstrated sections with denuded chronic granulation tissue showing a fibrotic stroma with numerous blood vessels and a mixed inflammatory infiltrate including scattered plasma cells. It is important to differentiate PCB from a syphilitic chancre in a patient presenting with a nonhealing penile lesion. This case report demonstrates that these entities may be seen in the same patient at different times.


The B cell response in multiple sclerosis.
Multiple sclerosis (MS) plaques and CSF contain increased amounts of intrathecally synthesized IgG, manifest as oligoclonal bands (OCBs) after protein electrophoresis. OCBs are not unique to MS and are also produced in infectious diseases of the CNS, in which the oligoclonal IgG has been shown to be antibody directed against the disease-causing agent. Thus, analysis of antibody specificity may identify the causative agent/antigen in MS. This review discusses recent studies that have analyzed the phenotypes of B cells in MS which infiltrate the CNS and the molecular features of their antigen-binding regions. Together with histologic studies showing the presence of ectopic lymphoid follicles in the meninges of some MS patients, this data supports the notion of a targeted and compartmentalized humoral response in MS.


Monoclonal antibodies multireactive with parasite antigens produced by hybridomas generated from naive mice.
Hybridoma clones producing IgM naturally occurring (natural) antibodies were generated from naive Balb/c mice and characterized for reactivity against parasite antigens. Ascites of mice injected with these hybridomas reacted with Toxoplasma gondii soluble antigen at levels approximately 1000-10,000 times higher than serum pooled from mice used for generating hybridomas as determined by a conventional enzyme-linked immunosorbent assay. Western blot analysis indicated that these monoclonal antibodies reacted with multiple antigen molecules of T. gondii with patterns similar to that of pooled mouse sera. These antibodies also reacted with multiple antigens of Plasmodium yoelii, Entamoeba histolytica, Ascaris lumbricoides, Toxocara canis, Trichuris vulpis, Fasciola hepatica, Schistosoma mansoni, and Dipylidium caninum. When one monoclonal antibody was absorbed with these parasite antigens, its reactivity with T. gondii antigen molecules was consistently reduced, independent of parasite species. These natural antibodies failed to kill T. gondii tachyzoites in vitro or to protect mice from lethal challenge with T. gondii. These results indicate that natural antibodies detected in sera of naive mice are secreted from certain B cell populations and that these antibodies are multireactive with parasite antigens and have low affinity.


Romantic relationship stages and social networking sites: uncertainty reduction strategies and perceived relational norms on facebook.
Due to their pervasiveness and unique affordances, social media play a distinct role in the development of modern romantic relationships. This study examines how a social networking site is used for information seeking about a potential or current romantic partner. In a survey, Facebook users (N=517) were presented with Facebook behaviors categorized as passive (e.g., reading a partner's profile), active (e.g., "friending" a common third party), or interactive (e.g., commenting on the partner's wall) uncertainty reduction strategies. Participants reported how normative they perceived these behaviors to be during four possible stages of relationship development (before meeting face-to-face, after meeting face-to-face, casual dating, and exclusive dating). Results indicated that as relationships progress, perceived norms for these behaviors change. Sex differences were also observed, as women perceived passive and interactive strategies as more normative than men during certain relationship stages.


Operative treatment of sacrococcygeal chordoma. A review of twenty-one cases.
Between 1972 and 1992, twenty-one patients had a primary operation for the treatment of a sacrococcygeal chordoma; seventeen had had a diagnostic biopsy elsewhere. The average age at the time of the operation was fifty-five years (range, six to seventy-eight years); fourteen patients were male and seven were female. In all patients, a posterior approach was used, even for resections at the cephalic levels of the sacrum. In addition, sixteen of the twenty-one patients were treated with adjuvant radiation therapy. Four patients died; three died of metastatic chordoma. Of the remaining seventeen patients, fifteen were apparently free of disease and had not had a local recurrence at the time of the latest follow-up examination. The average duration of follow-up for these fifteen patients was four and one-half years. Of the nine patients who were followed for at least five years, seven were disease-free at the latest follow-up evaluation. Of the seven patients in whom both second sacral roots were the most caudad nerve-roots spared, four had normal bladder control and five had normal bowel control. Of the four patients in whom the most caudad nerve-roots spared were the first sacral or more cephalic roots, all had impaired bladder control, one had impaired bowel control, and three had a colostomy.


Effects of NRG1 and DAOA genetic variation on transition to psychosis in individuals at ultra-high risk for psychosis.
Prospective studies have suggested genetic variation in the neuregulin 1 (NRG1) and D-amino-acid oxidase activator (DAOA) genes may assist in differentiating high-risk individuals who will or will not transition to psychosis. In a prospective cohort (follow-up=2.4-14.9 years) of 225 individuals at ultra-high risk (UHR) for psychosis, we assessed haplotype-tagging single-nucleotide polymorphisms (htSNPs) spanning NRG1 and DAOA for their association with transition to psychosis, using Cox regression analysis. Two NRG1 htSNPs (rs12155594 and rs4281084) predicted transition to psychosis. Carriers of the rs12155594 T/T or T/C genotype had a 2.34 (95% confidence interval (CI)=1.37-4.00) times greater risk of transition compared with C/C carriers. For every rs4281084 A-allele the risk of transition increased by 1.55 (95% CI=1.05-2.27). For every additional rs4281084-A and/or rs12155594-T allele carried the risk increased ∼1.5-fold, with 71.4% of those carrying a combination of 3 of these alleles transitioning to psychosis. None of the assessed DAOA htSNPs were associated with transition. Our findings suggest NRG1 genetic variation may improve our ability to identify UHR individuals at risk for transition to psychosis.


Intranasal administration of plasmid DNA-coated nanoparticles results in enhanced immune responses.
Intranasal immunization offers potential forthe elicitation of effective mucosal and systemic immune responses. In this study, a previously reported novel cationic nanoparticle engineered from a microemulsion precursor was further modified, optimized and applied intranasally to mice to explore its potential as a plasmid DNA (pDNA) vaccine delivery system. To this end, more uniform nanoparticles (around 100 nm) containing less cationic surfactant were developed. The pDNA-coated nanoparticles significantly enhanced the specific serum IgG and IgA titres to an expressed model antigen, beta-galactosidase, by 18-28 and 25-30 fold, respectively, when compared with naked pDNA alone. An enhanced splenocyte proliferative response was also observed after immunization with the pDNA-coated nanoparticles. It was concluded that these plasmid DNA-coated nanoparticles may have potential for immunization via the nasal route.


The effect of bone quality on pedicle screw loading in axial instability. A synthetic model.
In this biomechanical analysis of pedicle screw bending moments, custom-fabricated vertebral analogues were loaded in axial compression to produce sagittal bending forces. Moments were measured directly from internally instrumented pedicle screws. To establish the role of cancellous vertebral modulus on pedicle screw bending moments within the vertebral body and the vertebral pedicle. Pedicle screws are often used to manage axial instability of the spine. Clinical studies report a high incidence of screw bending failure, resulting in kyphosis and pain in some patients. Factors predisposing to bending failure are not well understood, although recent studies have shown that vertebral morphometry is important. Axially canullated 7.0-mm pedicle screws, internally instrumented with paired strain gauges, were inserted into analogue vertebrae of uniform dimension. Cancellous modulus was varied from 25-100 MPa. Screws were rigidly mounted to a vertical testing frame, and axial loads were applied to the superior vertebral endplate, producing sagittal bending moments. Moments were recorded from gauges applied in the intrapedicular and intravertebral portions of the screw. Mean moments were compared using a Student's t test, with significance defined as P < 0.05. Cancellous modulus did not affect bending moments experienced in either the intrapedicular or intravertebral portions of the pedicle screws. Gauge accuracy was excellent, and with no gauge drift. Although small changes in pedicle morphometry can alter screw bending moments significantly, changes in cancellous modulus had no measurable impact on bending moments at these same loads. Bone density is likely to play a limited role in screw bending failure.


The contaminant legacy from historic coastal landfills and their potential as sources of diffuse pollution.
Prior to modern environmental regulation landfills in low-lying coastal environments were frequently constructed without leachate control, relying on natural attenuation within inter-tidal sediments to dilute and disperse contaminants reducing environmental impact. With sea level rise and coastal erosion these sites may now pose a pollution risk, yet have received little investigation. This work examines the extent of metal contamination in saltmarsh sediments surrounding a historic landfill in the UK. Patterns of sediment metal data suggest typical anthropogenic pollution chronologies for saltmarsh sediments in industrialised nations. However, many metals were also enriched at depth in close proximity to the landfill boundary and are indicative of a historical leachate plume. Though this total metal load is low, e.g., c. 1200 and 1650kg Pb and Zn respectively, with >1000 historic landfills on flood risk or eroding coastlines in the UK this could represent a significant, yet under-investigated, source of diffuse pollution.


The effect of oral fenoldopam (SKF 82526-J), a peripheral dopamine receptor agonist, on blood pressure and renal function in normal man.
The effect of a single oral dose of 100 mg of fenoldopam on renal function and blood pressure was investigated in seven healthy male subjects in a double-blind placebo controlled study. Mean diastolic blood pressure fell by 10 mm Hg, 45 min after oral dosing and then gradually returned to baseline values. There was an increase in pulse rate and a delayed rise in systolic blood pressure. Measured from 30 to 120 min after drug ingestion, mean effective renal plasma flow increased to 158% of the value observed after placebo; mean glomerular filtration rate rose to 109% of the placebo value. Measured from 120 to 210 min after administration of the drug, effective renal plasma flow and glomerular filtration rate had returned to baseline values. Fenoldopam produced a small increase in the mean sodium excretion rate which was not significantly different from the fall after placebo. No change was detected in urine flow or potassium excretion rate. Mean plasma renin activity increased three-fold 1 h after oral dosing. Plasma aldosterone did not show a parallel increase although the plasma concentration at 1 h was significantly higher than after placebo. The results show a pronounced renal vasodilator effect lasting about 2 h. The findings are consistent with marked DA1 receptor agonist activity.


Application of Immunocompetent Microphysiological Systems in Drug Development: Current Perspective and Recommendations.
Immune responses are heavily involved in the regulation and pathogenesis of human diseases, including infectious diseases, inflammatory and autoimmune conditions, cancer, neurological disorders, and cardiometabolic syndromes. The immune system is considered a double-edged sword serving as a powerful host defense mechanism against infection and cancerous cells and causing detrimental tissue damage when the immune response is exaggerated or uncontrollable. One of the challenges in studying the efficacy and toxicity of drugs that target or modulate the immune system is the lack of suitable preclinical human models that are predictive of human response. Recent advancements in human microphysiological systems (MPS) have provided a promising in vitro platform to evaluate the response of immune organs ex vivo, to investigate the interaction of immune cells with non-lymphoid tissue cells, and to reduce the reliance on animals in preclinical studies. The development, regulation, trafficking, and responses of immune cells have been extensively studied in preclinical animal models and clinically, providing a wealth of knowledge by which to evaluate new in vitro models. Therefore, the application of immunocompetent MPS in drug discovery and development should first verify that the immune response in an MPS model recapitulates the complexity of the human immune physiology. This manuscript reviews biological functions of immune organ systems and tissue-resident immune cells and discusses contexts-of-use for commonly used immunocompetent and immune organ MPS models. Current perspective and recommendations are provided to guide the continued development of immune organ and immunocompetent MPS models and their application in drug discovery and development.


[Changes in the composition of phospholipids bound to supramolecular DNA of the thymus and liver in gamma-irradiated rats].
The composition of supramolecular DNA (SM DNA)-bound phospholipids (PL) of thymus and liver of intact rats and those 2 min, 2, 6 and 24 h after gamma-irradiation (9,7 Gy) was studied. In norm, supramolecular DNA of the thymus was shown to contain 6.7 micrograms PL/mg DNA, and that of the liver, 6.1 micrograms PL/mg DNA, the main components of PL being cardiolipin (CL) and phosphatidylethanolamine (PEA). Substantial changes were detected in the PL composition of SM DNA of gamma-irradiated rat organs. During the postirradiation period the concentration of PEA and CL in thymus SM DNA changed symbatically and irreversibly decreased to traces; whereas in SM DNA of the liver, their concentrations changed antibatically and decreased only to a definite level thus maintaining the necessary "lipid volume". It was shown that PL were not restored in SM DNA of the radioresistant liver.


A semi high-throughput method for real-time monitoring of curli producing Salmonella biofilms on air-solid interfaces.
Biofilms enable bacteria to colonize numerous ecological niches. Bacteria within a biofilm are protected by the extracellular matrix (ECM), of which the fibril-forming amyloid protein curli and polysaccharide cellulose are major components in members of Salmonella, Eschericha and Mycobacterium genus. A shortage of real-time detection methods has limited our understanding of how ECM production contributes to biofilm formation and pathogenicity. Here we present optotracing as a new semi-high throughput method for dynamic monitoring of Salmonella biofilm growth on air-solid interfaces. We show how an optotracer with binding-induced fluorescence acts as a dynamic fluorescent reporter of curli expression during biofilm formation on agar. Using spectrophotometry and microscopic imaging of fluorescence, we analyse in real-time the development of the curli architecture in relation to bacterial cells. With exceptional spatial and temporal precision, this revealed a well-structured, non-uniform distribution of curli organised in distally projecting radial channel patterns. Dynamic monitoring of the biofilm also showed defined regions undergoing different growth phases. ECM structures were found to assemble in regions of late exponential growth phase, suggesting that ECM forms on site after bacteria colonize the surface. As the optotracer biofilm method expedites screening of curli production, providing exceptional spatial-temporal understanding of the surface-associated biofilm lifestyle, this method adds a new technique to further our understanding of bacterial biofilms.


Evaluation of the Estrogenic/Antiestrogenic Activities of Perfluoroalkyl Substances and Their Interactions with the Human Estrogen Receptor by Combining In Vitro Assays and In Silico Modeling.
The potential estrogenic activities of perfluoroalkyl substances (PFASs) are controversial. Here, we investigated the estrogenic/antiestrogenic activities of PFASs and explored the corresponding interaction mode of PFASs with the estrogen receptor (ER) by combining in vitro assays and in silico modeling. We found that three PFASs (perfluorobutanoic acid, perfluorobutane sulfonate, and perfluoropentanoic acid) exerted antiestrogenic effects by inhibiting luciferase activity, whereas perfluorohexane sulfonate (PFHxS) and perfluorooctane sulfonate (PFOS) exerted estrogenic effects by inducing luciferase activity. When coexposed to 17β-estradiol (E2), all tested PFASs attenuated the E2-stimulated luciferase activity; unexpectedly, each PFAS could further attenuate the luciferase activity generated by the cotreatment with ICI 182,780 and E2, with a minimal effective concentration comparable to that found in human serum. PFHxS and PFOS significantly induced the gene expression of TFF1; additionally, all PFASs inhibited the E2-induced gene expression of TFF1 and EGR3. Furthermore, the results of the blind docking analyses suggested that the interaction with the coactivator-binding region on the ER surface should be included as a pathway through which PFASs exert estrogenic and antiestrogenic activities. Finally, we revealed the critical molecular property of the zero-order molecular connectivity index (MCI) (0χ) that affects the antiestrogenic activity of PFASs.


Improving glycemic control: the case for self-monitoring blood glucose levels.
Diabetes can be potentially identified, monitored, treated, and prevented more easily now than at any other time in history. Yet, the prevalence of diabetes continues to grow and the complications associated with it continue to afflict millions of Americans. Glycemic control, or the maintenance of appropriate levels of blood sugar, measured through the self-monitoring of blood glucose or a glycated hemoglobin test, represents the best opportunity for persons with diabetes to prevent complications by helping them understand the effect of their lifestyle choices and medications on their health. Despite the numerous advantages of glycemic control, a number of barriers prevent individuals from monitoring their blood sugar concentrations and achieving the health benefits that come with the proper understanding of their condition.


Binding of glutamine to glutamine-binding protein from Escherichia coli induces changes in protein structure and increases protein stability.
Glutamine-binding protein (GlnBP) from Escherichia coli is a monomeric protein localized in the periplasmic space of the bacterium. It is responsible for the first step in the active transport of L-glutamine across the cytoplasmic membrane. The protein consists of two similar globular domains linked by two peptide hinges, and X-ray crystallographic data indicate that the two domains undergo large movements upon ligand binding. Fourier transform infrared spectroscopy (FTIR) was used to analyze the structure and thermal stability of the protein in detail. The data indicate that glutamine binding induces small changes in the secondary structure of the protein and that it renders the structure more thermostable and less flexible. Detailed analyses of IR spectra show a lower thermal sensitivity of alpha-helices than beta-sheets in the protein both in the absence and in the presence of glutamine. Generalized two-dimensional (2D) analyses of IR spectra reveal the same sequence of unfolding events in the protein in the absence and in the presence of glutamine, indicating that the amino acid does not affect the unfolding pathway of the protein. The data give new insight into the structural characteristics of GlnBP that are useful for both basic knowledge and biotechnological applications.


[Analysis and visualization of diffusion tensor MRI].
In magnetic resonance imaging (MRI), the contrast mechanisms based on the water diffusion provide an understanding of the microscopic geometry of tissues and related tissue composition. To provide a general view of this rapidly developing area, the key concept in diffusion MRI and its potential applications are described. This article provides explains data acquisition of diffusion MRI, analysis, and visualization methods that are relevant to studying microstructure using diffusion tensor MRI.


Identification of key pathways and RNAs associated with skeletal muscle atrophy after spinal cord injury.
This study was performed to investigate the potential key molecules involved in the progression of skeletal muscle atrophy after SCI. Based on GSE21497 dataset, the DEmRNAs and DElncRNAs were screened after differentially expressed analysis. Then the enrichment analyses were performed on DEmRNAs. Then the PPI network and ceRNA network were constructed. Finally, the DGIdb was utilized to predict drug-gene interactions. A total of 412 DEmRNAs and 21 DElncRNAs were obtained. The DEmRNAs were significantly enriched in MAPK signaling pathway and FoxO signaling pathway. In addition, UBE2D1, JUN, and FBXO32 had higher node degrees in PPI network, and the top 20 genes with high degree were significantly enriched in FoxO signaling pathway and Endometrial cancer. Moreover, FOXO3 was regulated by hsa-miR-1207-5p and hsa-miR-1207-5p was regulated by lncRNA RP11-253E3.3 in ceRNA network. Finally, 37 drug-gene interactions were obtained based on the 26 genes in ceRNA network. UBE2D1, JUN, and FBXO32 are likely to be related to the progression of skeletal muscle atrophy after SCI, and activating of MAPK signaling pathway, Endometrial cancer and FoxO signaling pathway may induce skeletal muscle inflammation, apoptosis, autophagy and atrophy after SCI. Moreover, RP11-253E3.3-hsa-miR-1207-5p-FOXO3 axis may be a promising therapeutic target for skeletal muscle atrophy after SCI.


Better design of menu selection systems through cognitive psychology and human factors.
In this study, I seek to emphasize the contributions of cognitive psychology and human factors research in the design of menu selection systems. Menu selection systems are used in computer interfaces to allow users to enter choices, set parameters, and navigate to items, functions, and locations. Designers of these systems have many choices concerning the organizational structure and layout of the menu interface. I review several of these concerning hierarchies of menus, organization and clustering of items, and item distinctiveness. Special attention is given to cases in which designer's intuition differed from theory and experimental results. Cognitive psychology and human factors have contributed both theory and empirical research that have helped to resolve differences of opinion and establish general principles for design. It is argued that cognitive psychology has contributed substantially to the design of better menu selection systems. It is imperative that designers continue to apply these findings to interfaces that they develop and that researchers continue to study the characteristics and efficacy of innovative menu designs as they appear.


Hepatocellular carcinoma and vitamin D: a review.
The non-classical actions of vitamin D, namely antiproliferation, pro-differentiation, pro-apoptosis, anti-inflammation, and immune regulation, have received great attention during the past decade. Increasing evidence from epidemiological studies showing the inverse association between vitamin D status and incidence of many forms of cancer as well as biochemical studies has suggested that vitamin D deficiency may play a role in the cause and progression of these types of cancer. Recently, vitamin D and its analogs have been deemed as potential regimen to treat a variety of cancers alone or in combination with other drugs. Although, the epidemiologic evidence regarding the association of vitamin D and hepatocellular carcinoma (HCC) is still inconclusive, biochemical evidence clearly indicates that HCC cells are responsive to the inhibitory effect of vitamin D and its analogs. In this review, we discuss the current status of HCC and its treatment, the source, metabolism, functions, and the mechanism of actions of vitamin D, and the biochemical studies of vitamin D analogs and their implications in the prevention and treatment of HCC.


Reflection mode scanning near-field optical microscopy analyses of integrated devices.
Ultra-large-scale integrated devices have been investigated by a reflection mode scanning near-field optical microscope designed for semiconductor analyses. Although it could be found that imaging the reflectivity of metal structures buried underneath thin, optically transparent passivation layers is practicable, shading of the reflected light by the SNOM probe complicated the interpretability of the achieved results. This issue has been overcome by using the SNOM probe as both illumination source and detector, simultaneously. The application of focused ion beam milling to the probes has allowed the increase of the transmittivity of the probes to such an extent that coated fibres could be utilized and the interpretability of the results could be enhanced. Furthermore, the investigated structures are of great interest for an investigation of z-motion artefacts, as the presence of the polished passivation layers allows topographical influences to be distinguished from pure optical contrast.


Persistence of lymphoblasts in bone marrow on day 15 and days 22 to 25 of remission induction predicts a dismal treatment outcome in children with acute lymphoblastic leukemia.
We determined the prognostic importance of morphologically identifiable persistent disease at day 15 and days 22 to 25 of remission induction in childhood acute lymphoblastic leukemia (ALL). Among 546 patients entered on 2 consecutive protocols, 397 patients had evaluable bone marrow (BM) examinations on day 15 (+/- 1 day) and 218 on days 22 to 25 (+/- 1 day). Fifty-seven patients (14%) had persistent lymphoblasts (> or = 1%) in the BM on day 15 and 27 patients (5.5%) had persistent lymphoblasts on days 22 to 25. The 5-year event-free survival (EFS) was significantly worse for patients with lymphoblasts on day 15 (40% +/- 6%) or on days 22 to 25 (4% +/- 3%) as compared to those without lymphoblasts on these dates (78% +/- 2% and 76% +/- 2%, respectively, P <.001 for both comparisons). A worse prognosis was observed even for patients with a low percentage of lymphoblasts (ie, 1%-4%) at either day 15 (5-year EFS = 56% +/- 8%) or days 22 to 25 (5-year EFS = 0%) compared to those without morphologically identifiable persistent lymphoblasts at these times (P <.001 for both comparisons). The prognostic impact of persistent lymphoblasts on both dates remained significant after adjusting for other known risk factors, including treatment protocol, age, white blood cell count, DNA index, cell lineage, and central nervous system status, and National Cancer Institute/Rome criteria simultaneously. Hence, persistence of lymphoblasts (even 1%-4%) on day 15 of remission induction was associated with a poor prognosis and on days 22 to 25 signified a particularly dismal outcome; these very high-risk patients require novel or more intensive therapy to improve outcome.


Chiral Brønsted acid catalyzed enantioselective propargylation of aldehydes with allenylboronate.
A highly enantioselective chiral Brønsted acid catalyzed propargylation of aldehydes with allenylboronate is described. The reaction is shown to be practical and quite general with a broad substrate scope covering aryl, polyaryl, heteroaryl, α,β-unsaturated, and aliphatic aldehydes.


Joint effect of MCP-1 genotype GG and MMP-1 genotype 2G/2G increases the likelihood of developing pulmonary tuberculosis in BCG-vaccinated individuals.
We previously reported that the -2518 MCP-1 genotype GG increases the likelihood of developing tuberculosis (TB) in non-BCG-vaccinated Mexicans and Koreans. Here, we tested the hypothesis that this genotype, alone or together with the -1607 MMP-1 functional polymorphism, increases the likelihood of developing TB in BCG-vaccinated individuals. We conducted population-based case-control studies of BCG-vaccinated individuals in Mexico and Peru that included 193 TB cases and 243 healthy tuberculin-positive controls from Mexico and 701 TB cases and 796 controls from Peru. We also performed immunohistochemistry (IHC) analysis of lymph nodes from carriers of relevant two-locus genotypes and in vitro studies to determine how these variants may operate to increase the risk of developing active disease. We report that a joint effect between the -2518 MCP-1 genotype GG and the -1607 MMP-1 genotype 2G/2G consistently increases the odds of developing TB 3.59-fold in Mexicans and 3.9-fold in Peruvians. IHC analysis of lymph nodes indicated that carriers of the two-locus genotype MCP-1 GG MMP-1 2G/2G express the highest levels of both MCP-1 and MMP-1. Carriers of these susceptibility genotypes might be at increased risk of developing TB because they produce high levels of MCP-1, which enhances the induction of MMP-1 production by M. tuberculosis-sonicate antigens to higher levels than in carriers of the other two-locus MCP-1 MMP-1 genotypes studied. This notion was supported by in vitro experiments and luciferase based promoter activity assay. MMP-1 may destabilize granuloma formation and promote tissue damage and disease progression early in the infection. Our findings may foster the development of new and personalized therapeutic approaches targeting MCP-1 and/or MMP-1.


Delayed activation of the plasma membrane calcium pump by a sudden increase in Ca2+: fast pumps reside in fast cells.
There are four genes encoding isoforms of the plasma membrane Ca(2+) pump (PMCA). PMCA variability is increased by the presence of two splicing sites. Functional differences between the variants of PMCA have been described, but little is known about the adaptive advantages of this great diversity of pumps. In this paper we studied how the different isoforms respond to a sudden increase in Ca(2+) concentration. We found that different PMCAs are activated by Ca(2+) at different rates, PMCA 3f and 2a being the fastest, and 4b the slowest. The rate of activation by Ca(2+) depends both on the rate of calmodulin binding and the magnitude of the activation by calmodulin. We found that 2a is located in heart and the stereocilia of inner ear hair cells, 3f in skeletal muscle and 4b was identified in Jurkat cells. Both cardiac and skeletal muscle, and stereocilia recover very rapidly after a cytoplasmic Ca(2+)peak, while in Jurkat cells the recovery takes up to a minute. In stereocilia, 2a is the only method for export of Ca(2+), making the analysis of them unusually straightforward. This indicates that these rates of PMCA activation by Ca(2+) are correlated with the speed of Ca(2+) concentration decay after a Ca2 spike in the cells in which these variants of PMCA are expressed. The results suggest that the type of PMCA expressed will correspond with the speed of Ca(2+) signals in the cell.


Early recognition of patients with decreased methotrexate clearance following high-dose methotrexate infusion therapy.
The purpose of this study was to identify the patients with decreased methotrexate (MTX) clearance as early as possible after the start of high-dose methotrexate (HD-MTX) infusion. Fifty-six patients (age: 18 approximately 83 years) received a HD-MTX infusion (dosage: 1.9 approximately 3.8 g/m2) for 6 h. These patients were retrospectively divided into a low-clearance group and a high-clearance group based on the serum MTX concentration at 48 h (1 microM). Six out of the 56 patients showed decreased MTX clearance. The MTX concentrations in the low-clearance group were significantly higher than those in the high-clearance group even in earlier sampling times than at 48 h. The average MTX concentrations were 330 microM at 6 h, 72 microM at 12 h, and 16 microM at 24 h in the low-clearance group, and those in the high-clearance group were 210 microM, 18 microM, and 1.0 microM, respectively. The estimated elimination half-lives (t1/2) at 6 approximately 12 h and 12 approximately 24 h after the start of the infusion were also significantly longer in the low-clearance group (2.8 vs. 1.7 h and 5.0 vs. 2.8 h, respectively). Therefore, we proposed convenient criteria based on the mean + 1 S.D. of the high-clearance group: the concentration > 270 microM at 6 h and > 32 microM at 12 h; the t1/2 value > 2.1 h at 6-12 h. All 6 patients were recognized as belonging to the low-clearance group at an early stage after HD-MTX infusion by using our proposed criteria. These results indicate that patients with decreased MTX clearance could be identified within the first 12 h after the start of HD-MTX infusion. The factors influencing the prolonged elimination of MTX were also investigated. A significant decrease in renal function on day 2 was observed in the low-clearance group. The MTX level at 12 h and the estimated t1/2 values were significantly correlated with BUN, Scr and Clcr on the 2nd day after HD-MTX therapy, suggesting that an alteration in renal function occurs within 12 h of the HD-MTX infusion. The prolonged elimination of MTX could be attributable to this decrease in renal function.


Prenatal diagnosis: molecular genetics and cytogenetics.
The technologies developed for the Human Genome Project, the recent surge of available DNA sequences resulting from it and the increasing pace of gene discoveries and characterization have all contributed to new technical platforms that have enhanced the spectrum of disorders that can be diagnosed prenatally. The importance of determining the disease-causing mutation or the informativeness of linked genetic markers before embarking upon a DNA-based prenatal diagnosis is, however, still emphasized. Different fluorescence in situ hybridization (FISH) technologies provide increased resolution for the elucidation of structural chromosome abnormalities that cannot be resolved by more conventional cytogenetic analyses, including microdeletion syndromes, cryptic or subtle duplications and translocations, complex rearrangements involving many chromosomes, and marker chromosomes. Interphase FISH and the quantitative fluorescence polymerase chain reaction are efficient tools for the rapid prenatal diagnosis of selected aneuploidies, the latter being considered to be most cost-effective if analyses are performed on a large scale. There is some debate surrounding whether this approach should be employed as an adjunct to karyotyping or whether it should be used as a stand-alone test in selected groups of women.


Prognostic significance of detection of monoclonality in remission marrow in acute lymphoblastic leukemia in childhood. Australian and New Zealand Children's Cancer Study Group.
Techniques based on the polymerase chain reaction (PCR) to detect rearrangement of the immunoglobulin or T-cell receptor genes can detect residual disease in leukemia and hence have the potential to improve prognosis and treatment. Such techniques may involve either detection of monoclonality, which is simple and quick but has limited sensitivity, or specific detection of the leukaemic clone, which is complex and time-consuming but has high sensitivity. The PCR was used to detect monoclonal rearrangements of the immunoglobulin heavy chain and/or T-cell receptor gamma chain genes in archival marrow specimens from 185 children with acute lymphoblastic leukemia who achieved remission during two consecutive Australasian trials of treatment. A monoclonal rearrangement was detected at diagnosis in 152 (84%) patients and in these patients detection of the same rearrangement in the remission marrow at the end of induction therapy was highly significantly correlated with outcome. There were nine patients in whom polymerase chain reaction showed only the monoclonal rearrangement and eight (89%) relapsed; there were 26 patients in whom PCR showed the leukemic monoclonal rearrangement as well as polyclonal rearrangements from normal lymphocytes and 12 (46%) relapsed; and there were 117 patients in whom only polyclonal rearrangements could be detected and only 29 (25%) relapsed. In patients who relapsed, remissions were shorter in those patients in whom the leukemic rearrangements had been detected in the remission marrow. Treatment in the later trial was more intensive than in the earlier trial, the results were better and the PCR detected the leukemic rearrangement in the remission marrow in significantly fewer patients. We conclude that detection by PCR of the monoclonal gene rearrangement of the leukemic clone in remission marrow indicates that numerous leukemic cells have survived induction therapy and is a good predictor of relapse. However, due to limited sensitivity of the test, failure to detect the leukemic clone by PCR is not a sufficiently good predictor of ultimate cure.


No useful role for fine needle aspiration as a marker for familial breast cancer.
A study of a single fine needle aspiration taken from the upper outer quadrant of 228 asymptomatic women attending a family history clinic has been performed. No abnormalities were detected. This is not a useful screening tool in asymptomatic women at risk of breast cancer.


Differential expression of extracellular matrix genes in glenohumeral capsule of shoulder instability patients.
Anterior shoulder instability is a common orthopedic problem. After a traumatic shoulder dislocation, patients present a plastic deformation of the capsule. The shoulder instability biology remains poorly understood. We evaluated the expression of genes that encode the cartilage oligomeric matrix protein (COMP), fibronectin 1 (FN1), tenascin C (TNC) and tenascin XB (TNXB) in the glenohumeral capsule of anterior shoulder instability patients and controls. Moreover, we investigated the associations between gene expression and clinical parameters. The gene expression was evaluated by quantitative reverse transcription-polymerase chain reaction in the antero-inferior (macroscopically injured region), antero-superior and posterior regions of the capsule of 29 patients with shoulder instability and 8 controls. COMP expression was reduced and FN1 and TNC expression was increased in the antero-inferior capsule region of cases compared to controls (p < 0.05). TNC expression was increased in the posterior capsule portion of shoulder instability patients (p = 0.022). COMP expression was reduced in the antero-inferior region compared to the posterior region of shoulder instability patients (p = 0.007). In the antero-inferior region, FN1 expression was increased in the capsule of patients with more than one year of symptoms (p = 0.003) and with recurrent dislocations (p = 0.004) compared with controls. FN1 and TNXB expression was correlated with the duration of symptoms in the posterior region (p < 0.05). Thus, COMP, FN1, TNC and TNXB expression was altered across the capsule of shoulder instability patients. Dislocation episodes modify FN1, TNC and TNXB expression in the injured tissue. COMP altered expression may be associated with capsule integrity after shoulder dislocation, particularly in the macroscopically injured portion.


Emotional attention in acquired prosopagnosia.
The present study investigated whether emotionally expressive faces guide attention and modulate fMRI activity in fusiform gyrus in acquired prosopagnosia. Patient PS, a pure case of acquired prosopagnosia with intact right middle fusiform gyrus, performed two behavioral experiments and a functional imaging experiment to address these questions. In a visual search task involving face stimuli, PS was faster to select the target face when it was expressing fear or happiness as compared to when it was emotionally neutral. In a change detection task, PS detected significantly more changes when the changed face was fearful as compared to when it was neutral. Finally, an fMRI experiment showed enhanced activation to emotionally expressive faces and bodies in right fusiform gyrus. In addition, PS showed normal body-selective activation in right fusiform gyrus, partially overlapping the fusiform face area. Together these behavioral and neuroimaging results show that attention was preferentially allocated to emotional faces in patient PS, as observed in healthy subjects. We conclude that systems involved in the emotional guidance of attention by facial expression can function normally in acquired prosopagnosia, and can thus be dissociated from systems involved in face identification.


Synergetic Photo-Thermo Catalytic Hydrogen Production by Carbon Materials.
Photo-thermo catalytic hydrogen production represents one of the most promising routes for channeling solar energy but typically suffers from high reaction temperatures. In this work, we develop photo-thermo catalytic hydrogen production at low temperatures by cost-effective, nonplasmonic, and metal-free nitrogen-doped carbon materials (CNO1-x). We demonstrate that due to the photothermal conversion of CNO1-x, carrier generation is improved and electron migration is enhanced to suppress the recombination of electron-hole pairs, both of which promote hydrogen production by photocatalysis, while generated hydrogen radicals facilitate the regeneration of active sites for hydrogen production by thermocatalysis. Such synergy greatly promotes photo-thermo catalytic hydrogen production at low temperatures. These results demonstrate the great promise of photo-thermo catalytic hydrogen production over carbon materials at low temperatures.


Coronally Advanced Flap with Different Designs in the Treatment of Gingival Recession: A Comparative Controlled Randomized Clinical Trial.
The aim of this parallel double-blind randomized controlled clinical trial was to describe a modified approach using the coronally advanced flap (CAF) with triangular design and to compare its efficacy, in terms of root coverage and esthetics, with a trapezoidal type of CAF. A sample of 50 isolated Miller Class I and II gingival recessions with at least 1 mm of keratinized tissue apical to the defects were treated with CAF. Of these recessions, 25 were randomly treated with trapezoidal CAF (control group) while the other 25 (test group) were treated with a modified triangular CAF. The clinical and esthetic evaluations, made by the patient and an independent periodontist, were performed 3 months, 6 months, and 1 year after the surgery. No statistically significant difference was demonstrated between the two CAF groups in terms of recession reduction, complete root coverage, or 6-month and 1-year patient esthetic scores. Better 3-month patient esthetic evaluations and better periodontist root coverage, color match, and contiguity assessments were reported after triangular CAF. Trapezoidal CAF was associated with greater incidence of keloid formation. Single-type gingival recessions can be successfully covered with both types of CAF. The triangular CAF should be preferred for esthetically demanding patients.


Management of portal hypertension severe complications.
Portal hypertension is a clinical syndrome characterized by an increase in the portal pressure gradient, defined as the gradient between the portal vein at the site downstream of the site of obstruction and the inferior vena cava. The most frequent cause of portal hypertension is cirrhosis. In patients with cirrhosis, portal hypertension is the main driver of cirrhosis progression and development of hepatic decompensation (ascites, variceal hemorrhage and hepatic encephalopathy), which defines the transition from compensated to decompensated stage. In decompensated patients, treatments aim at lowering the risk of death by preventing further decompensation and/or development of acute-on-chronic liver failure. Decompensated patients often pose a complex challenge which typically requires a multidisciplinary approach. The aims of the present review were to discuss the current knowledge regarding interventional treatments for patients with portal hypertension complications as well as to highlight useful information to aid hepatologists in their clinical practice. Specifically, we discussed the indications and contraindications of transjugular intra-hepatic portosystemic shunt and for the treatment of gastro-esophageal variceal hemorrhage in patients with decompensated cirrhosis (first section); we reviewed the use of interventional treatments in patients with hepatic vein obstruction (Budd-Chiari Syndrome) and in those with portal vein thrombosis (second section); and we briefly comment on the most frequent applications of selective splenic embolization in patients with and without underlying cirrhosis (third section).


The effects of dietary protein deficiency on rat testicular function.
Diets containing 0%, 5% and 10% protein were used for treatment periods of 30, 50, and 90 days respectively. Control rats were fed a diet containing 20% protein. Protein deficient rats failed to gain weight during the experiment. In addition, the weights of the testis, epididymis, prostate and seminal vesicle also decreased, with the 10% group less affected than the 0% and 5% groups. Testicular histology indicated retarded germ cell maturation in the 0% and 5% groups only. Overall testicular cell number and size were reduced in treated rats and there was a reduction in the diameter of the seminiferous tubule in these groups. Epididymal epithelial height was also reduced in protein deficient rats with a concomitant increase in the number of epididymal duct cross sections devoid of sperm. Protein deficiency caused significant reductions in testicular DNA, RNA and protein content. The proportion of motile epididymal sperm decreased in the 0% and 5% groups by 90% and 35% respectively. Epididymal sperm number decreased in both the 0% and 5% groups by 90% while the proportion of abnormal sperm increased by 65% and 61% respectively. Circulating androgen levels were also lowered by more than 50% on average in protein deficient animals.


Prevalence and Correlates of Phenazine Resistance in Culturable Bacteria from a Dryland Wheat Field.
Phenazines are a class of bacterially produced redox-active natural antibiotics that have demonstrated potential as a sustainable alternative to traditional pesticides for the biocontrol of fungal crop diseases. However, the prevalence of bacterial resistance to agriculturally relevant phenazines is poorly understood, limiting both the understanding of how these molecules might shape rhizosphere bacterial communities and the ability to perform a risk assessment for off-target effects. Here, we describe profiles of susceptibility to the antifungal agent phenazine-1-carboxylic acid (PCA) across more than 100 bacterial strains isolated from a wheat field where PCA producers are indigenous and abundant. We found that Gram-positive bacteria are typically more sensitive to PCA than Gram-negative bacteria, and there was significant variability in susceptibility both within and across phyla. Phenazine-resistant strains were more likely to be isolated from the wheat rhizosphere, where PCA producers were also more abundant, compared to bulk soil. Furthermore, PCA toxicity was pH-dependent for most susceptible strains and broadly correlated with PCA reduction rates, suggesting that uptake and redox-cycling were important determinants of phenazine toxicity. Our results shed light on which classes of bacteria are most likely to be susceptible to phenazine toxicity in acidic or neutral soils. In addition, the taxonomic and phenotypic diversity of our strain collection represents a valuable resource for future studies on the role of natural antibiotics in shaping wheat rhizosphere communities. IMPORTANCE Microbial communities contribute to crop health in important ways. For example, phenazine metabolites are a class of redox-active molecules made by diverse soil bacteria that underpin the biocontrol of diseases of wheat and other crops. Their physiological functions are nuanced. In some contexts, they are toxic. In others, they are beneficial. While much is known about phenazine production and the effect of phenazines on producing strains, our ability to predict how phenazines might shape the composition of environmental microbial communities is poorly constrained. In addition, phenazine prevalence in the rhizosphere has been predicted to increase in arid soils as the climate changes, providing an impetus for further study. As a step toward gaining a predictive understanding of phenazine-linked microbial ecology, we document the effects of phenazines on diverse bacteria that were coisolated from a wheat rhizosphere and identify conditions and phenotypes that correlate with how a strain will respond to phenazines.


Antitumor effects of deracoxib treatment in 26 dogs with transitional cell carcinoma of the urinary bladder.
OBJECTIVE-To evaluate the antitumor activity and toxic effects of deracoxib, a selective cyclooxygenase-2 inhibitor, in dogs with transitional cell carcinoma (TCC) of the urinary bladder. DESIGN-Clinical trial. Animals-26 client-owned dogs with naturally occurring, histologically confirmed, measurableTCC of the urinary bladder. PROCEDURES-Dogs were treated PO with deracoxib at a dosage of 3 mg/kg/d (1.36 mg/lb/d) as a single-agent treatment for TCC. Tumor response was assessed via radiography, abdominal ultrasonography, and ultrasonographic mapping of urinary bladder masses. Toxic effects of deracoxib administration in dogs were assessed through clinical observations and hematologic and biochemical analyses. RESULTS-Of 24 dogs for which tumor response was assessed, 4 (17%) had partial remission, 17 (71%) had stable disease, and 3 (13%) had progressive disease; initial response could not be assessed in 2 of 26 dogs. The median survival time was 323 days. Median time to progressive disease was 133 days. Renal, hepatic, and gastrointestinal abnormalities attributed to deracoxib administration were noted in 4% (1/26), 4% (1/26), and 19% (5/26) of dogs, respectively. CONCLUSIONS AND CLINICAL RELEVANCE-Results indicated that deracoxib was generally well tolerated by dogs and had antitumor activity against TCC.


Formation pathway of CuInSe2 nanocrystals for solar cells.
Copper, indium, and gallium chalcogenide nanocrystals (binary, ternary, and quaternary) have been used to fabricate high-efficiency thin-film solar cells. These solution-based methods are being scaled-up and may serve as the basis for the next generation of low-cost solar cells. However, the formation pathway to reach stoichiometric ternary CuInSe(2) or any chalcopyrite phase ternary or quaternary nanocrystal in the system has not been investigated but may be of significant importance to improving nanocrystal growth and discovering new methods of synthesis. Here, we present the results of X-ray diffraction, electron microscopy, compositional analysis, IR absorption, and mass spectrometry that reveal insights into the formation pathway of CuInSe(2) nanocrystals. Starting with CuCl, InCl(3), and elemental Se all dissolved in oleylamine, the overall reaction that yields CuInSe(2) involves the chlorination of the hydrocarbon groups of the solvent. Further, we show that the amine and alkene functional groups in oleylamine are not necessary for the formation of CuInSe(2) nanocrystals by conducting successful syntheses in 1-octadecene and octadecane. Hence, the role of oleylamine is not limited to nanocrystal size and morphology control; it also acts as a reactant in the formation pathway. Typically, the formation of copper selenide (CuSe) and indium selenide (InSe) nanocrystals precedes the formation of CuInSe(2) nanocrystals in oleylamine. But it was also found that Cu(2-x)Se (0 < x < 0.5) and In(2)Se(3) were the primary intermediates involved in the formation of CISe in a purely non-coordinating solvent such as 1-octadecene, which points to the surface-stabilization effect of the coordinating solvent on the less thermodynamically stable indium selenide (InSe) nanocrystals. We also show that the yield of the chalcopyrite phase of CuInSe(2) (as opposed to the sphalerite phase) can be increased by reacting CuSe nanocrystals with InCl(3).


Identification of genes for normalization of quantitative real-time PCR data in ovarian tissues.
Increased attention has been paid to the determination of the potential biomarker and therapeutic target for ovarian cancer in recent years. However, the normalization of quantitative real-time PCR is important to obtain accurate gene expression data. We investigated the stability of 20 reference genes in ovarian tissues under different conditions to determine the most adequate for this application. The study characterized the expression of 20 possible reference genes among 52 ovarian tissue samples involving the normal, non-malignant, and primary ovarian carcinomas. One-way analysis of variance (ANOVA) method was used to compare the candidate gene changes brought about by the disease progression. The stability and suitability of the genes with no statistic difference were further validated employing geNorm and NormFinder softwares. Results showed that the expression levels of the 20 reference genes varied, while the RPL4, RPLP0, HSPCB, TPT1, RPL13A, 18S rRNA, PPIA, TBP, and GUSB kept statistic stability despite different ovarian tissue conditions. RPL4, RPLP0, and HSPCB were demonstrated as the most stable reference genes and the combination of the RPLP0 and RPL4 should be recommended as a much more reliable normalization strategy.