Serum vitamin D levels in kidney transplant recipients: the importance of an immunosuppression regimen and sun exposure.
Vitamin D deficiency was shown to be prevalent among renal transplant recipients in northern countries, but little is known regarding risk factors. To test vitamin D levels in kidney transplant recipients residing closer to the equator, compare them to levels in liver transplant recipients and hemodialysis patients, and identify possible risk factors. In a cross-sectional study 103 kidney transplant recipients, 27 liver transplant recipients and 50 hemodialysis patients followed at our institute were tested for vitamin D levels. Demographic data, medical history and current treatment were recorded from the medical files. Inadequate vitamin D levels (< 30 ng/ml) were found in 75% of all patients and 75% of all kidney transplant recipients. Vitamin D levels were higher among dialysis patients than transplant recipients, though deficiency rates were similar. No association was found between kidney function and vitamin deficiency. Deficiency was associated with higher prednisone doses, use of mycophenolate sodium, tacrolimus, and iron supplements, or lower doses of vitamin D supplementation. Despite potential higher ultraviolet B exposure, inadequate vitamin D levels were prevalent in our study group. Importantly, some immunosuppressive medications were associated with vitamin D deficiency and high doses of vitamin D were associated with less deficiency.


Gas chromatographic analysis of resveratrol in plasma, lipoproteins and cells after in vitro incubations.
Resveratrol is a trihydroxystilbene present in certain red wines. It may play a role in the inhibition of lipoprotein oxidation and platelet activity. We have developed the first method to measure resveratrol in animal and human samples and to study its incorporation in vitro. After adding epicoprostanol as an internal standard, samples are subjected to lipid extraction in the presence of antioxidant and under dim light to minimize both denaturation and isomerization of the trans-resveratrol to the cis-form. Extracts were purified by cold acetone precipitation and the resveratrol-containing acetone phase was evaporated under nitrogen. The resveratrol was analyzed as a trimethylsilyl derivative by capillary gas chromatography which resolved the cis- and trans-resveratrol (6.6 and 12.9 min, respectively). Analyses of samples spiked with pure trans-resveratrol (0.1 to 10 microg) indicated that the method was specific and gave excellent linearity and recovery (96.8%) with a high reproducibility (coefficient of variation: 3.3%). The detection limit was about 50 ng/ml. Applications show that resveratrol was incorporated into blood cells and lipoproteins after in vitro incubations with plasma, lipoproteins and cells.


Home monitoring with connected mobile devices for asthma attack prediction with machine learning.
Monitoring asthma is essential for self-management. However, traditional monitoring methods require high levels of active engagement, and some patients may find this tedious. Passive monitoring with mobile-health devices, especially when combined with machine-learning, provides an avenue to reduce management burden. Data for developing machine-learning algorithms are scarce, and gathering new data is expensive. A few datasets, such as the Asthma Mobile Health Study, are publicly available, but they only consist of self-reported diaries and lack any objective and passively collected data. To fill this gap, we carried out a 2-phase, 7-month AAMOS-00 observational study to monitor asthma using three smart-monitoring devices (smart-peak-flow-meter/smart-inhaler/smartwatch), and daily symptom questionnaires. Combined with localised weather, pollen, and air-quality reports, we collected a rich longitudinal dataset to explore the feasibility of passive monitoring and asthma attack prediction. This valuable anonymised dataset for phase-2 of the study (device monitoring) has been made publicly available. Between June-2021 and June-2022, in the midst of UK's COVID-19 lockdowns, 22 participants across the UK provided 2,054 unique patient-days of data.


Prophylaxis and management of acute radiation-induced skin reactions: a systematic review of the literature.
Radiation therapy is a common treatment for cancer patients. One of the most common side effects of radiation is acute skin reaction (radiation dermatitis) that ranges from a mild rash to severe ulceration. Approximately 85% of patients treated with radiation therapy will experience a moderate-to-severe skin reaction. Acute radiation-induced skin reactions often lead to itching and pain, delays in treatment, and diminished aesthetic appearance-and subsequently to a decrease in quality of life. Surveys have demonstrated that a wide variety of topical, oral, and intravenous agents are used to prevent or to treat radiation-induced skin reactions. We conducted a literature review to identify trials that investigated products for the prophylaxis and management of acute radiation dermatitis. Thirty-nine studies met the pre-defined criteria, with thirty-three being categorized as prophylactic trials and six as management trials.For objective evaluation of skin reactions, the Radiation Therapy Oncology Group criteria and the U.S. National Cancer Institute Common Toxicity Criteria were the most commonly used tools (65% of the studies). Topical corticosteroid agents were found to significantly reduce the severity of skin reactions; however, the trials of corticosteroids evaluated various agents, and no clear indication about a preferred corticosteroid has emerged. Amifostine and oral enzymes were somewhat effective in preventing radiation-induced skin reactions in phase II and phase III trials respectively; further large randomized controlled trials should be undertaken to better investigate those products. Biafine cream (Ortho-McNeil Pharmaceuticals, Titusville, NJ, U.S.A.) was found not to be superior to standard regimes in the prevention of radiation-induced skin reactions (n = 6).In conclusion, the evidence is insufficient to support the use of a particular agent for the prevention and management of acute radiation-induced skin reactions. Future trials should focus on comparing agents and approaches that, in phase I and II trials, suggest efficacy. These future phase III randomized controlled trials must clearly distinguish between preventive and management strategies for radiation-induced dermatitis. Only then can evidence-based guidelines be developed, with the hope of standardizing the approach across centres and of improving the prevention and management of radiation-induced dermatitis.


A review of major influences on current public health policy in developed countries in the second half of the 20th century.
Public health policy underwent substantial transformation during the latter half of the 20th century. The landmark statement was the 1948 World Health Organization (WHO) constitution, which identified good health as a fundamental right and gave the responsibility to governments to achieve it for all their people. However, following World War II, developed countries made substantial investment in health care with less attention paid to public health. The importance of public health was slowly recognised over the period from 1970 to 2000 with the publication of several reports from different organisations. The first authoritative policy statement that the important determinants of health lay outside health care was in the Lalonde Report from Canada. These ideas were subsequently expressed in the WHO Alma-Ata declaration and were emphasised a year later by the US Surgeon General. The idea of setting goals for health improvement also began in the 1970s. The Lalonde Report and the United Kingdom Black Report recommended that targets be used, but the first explicitly stated health targets were set by the US in 1979. WHO also identified the need for such targets at this time, but did not introduce them until 1984. Since then health targets have become a central feature of public health policy in developed countries. The Ottawa Conference on Health Promotion in 1986 championed the view that health promotion was central to achieving health goals internationally. It helped clarify the types of actions needed: that individuals need to be provided with the supportive environment and economic resources to be able to lead healthy lives. In a further development, the Healthy Cities Project was launched with the specific aim of involving political decision-makers in building a strong lobby for public health at the local level. The Healthy Cities Project illustrates how to provide means and opportunity for interventions to be implemented in communities. Concerns with inequalities in health were emphasised in the WHO declaration of Alma-Ata, and were the focus of the United Kingdom Black Report. The Jakarta Conference on Health Promotion in 1997 urged international action on poverty, as it is the major threat to health. International acceptance of the need to tackle inequalities took longer than the acceptance of health targets, but it is now an important feature of public health policy. The advent of the 21st century marked the coming of age of public health. The renewed version of 'Health for All', 'Health for All in the 21st Century', emphasised the one constant goal of WHO that all individuals should achieve their full health potential. Public health is now regarded internationally as being a priority with this WHO goal being adopted as the overarching goal of policy. The challenges it faces in tackling problems such as obesity, inequalities in health, smoking, alcohol and substance abuse are great and will require policies which tackle the economic, social and environmental determinants of health.


Inhibition of pathogenic microbes in oral infectious diseases by natural products: Sources, mechanisms, and challenges.
The maintenance of oral health is of utmost importance for an individual's holistic well-being and standard of living. Within the oral cavity, symbiotic microorganisms actively safeguard themselves against potential foreign diseases by upholding a multifaceted equilibrium. Nevertheless, the occurrence of an imbalance can give rise to a range of oral infectious ailments, such as dental caries, periodontitis, and oral candidiasis. Presently, clinical interventions encompass the physical elimination of pathogens and the administration of antibiotics to regulate bacterial and fungal infections. Given the limitations of various antimicrobial drugs frequently employed in dental practice, the rising incidence of oral inflammation, and the escalating bacterial resistance to antibiotics, it is imperative to explore alternative remedies that are dependable, efficacious, and affordable for the prevention and management of oral infectious ailments. There is an increasing interest in the creation of novel antimicrobial agents derived from natural sources, which possess attributes such as safety, cost-effectiveness, and minimal adverse effects. This review provides a comprehensive overview of the impact of natural products on the development and progression of oral infectious diseases. Specifically, these products exert their influences by mitigating dental biofilm formation, impeding the proliferation of oral pathogens, and hindering bacterial adhesion to tooth surfaces. The review also encompasses an examination of the various classes of natural products, their antimicrobial mechanisms, and their potential therapeutic applications and limitations in the context of oral infections. The insights garnered from this review can support the promising application of natural products as viable therapeutic options for managing oral infectious diseases.


Zinc oxide nanoparticles as contrast-enhancing agents for microwave imaging.
Microwave imaging/sensing is an emerging technology that shows potential for healthcare diagnostic applications, particularly in breast cancer detection. This technique estimates the anatomically variant dielectric properties of the breast. Similar to other imaging modalities, nanoparticles (NPs) could potentially be utilized as contrast agents to increase contrast between healthy and malignant tissues. In this study, aqueous suspensions of NPs such as surface-modified single-walled carbon nanotubes, zinc oxide, and silicon dioxide are studied to assess their potential effective contrast for microwave imaging. Morphology characterization of the NPs has been achieved using atomic force microscopy (AFM) and scanning electron microscopy (SEM). The size and stability of colloidal dispersions have been characterized by dynamic light scattering technique (DLS) and Ultraviolet-visible spectrophotometry (UV-Vis). The dielectric characterization of the aqueous-based colloidal suspensions is recorded over the microwave frequency range between 1 and 4 GHz. Zinc oxide NP dispersion has shown an increase in the dielectric constant compared to the background medium. Furthermore, PEGylation of ZnO NPs can achieve a valid increase in the dielectric constant compared to water, which was shown to be concentration dependent. These results suggest that ZnO nanomaterials have the potential to be used in biomedical applications such as breast imaging to improve diagnostic capabilities.


Transcatheter Arterial Embolization Containing Donafenib Induces Anti-Angiogenesis and Tumoricidal CD8+ T-Cell Infiltration in Rabbit VX2 Liver Tumor.
To evaluate the effect and immune response of transcatheter arterial embolization (TAE) combined with donafenib in rabbit VX2 liver tumor model. Thirty-six New Zealand white rabbits with VX2 liver tumor were randomly divided into three groups. The LD group was treated with the emulsion of 0.5 mL lipiodol and 4 mg donafenib via hepatic arterial administration. The LE group was treated with the emulsion of 0.5 mL lipiodol and 4 mg epirubicin. The control group was treated with the equal volume of saline. Four rabbits were euthanized in each group on day 1, 3 and 7 after treatment. The tumor growth, histological markers associated with angiogenesis and immune response were assessed by imaging and histopathology. In addition, immune modulatory cytokines included interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and biochemical hepatorenal function were measured. Compared to other groups, LD group achieved lower tumor growth rate, fewer metastatic lesions, and higher tumor necrosis rate on day 7 after treatment. The percentage of CD31-positive area in the LD group was significantly lower than that in the LE group on day 3 and 7 after treatment. In addition, CD8+ lymphocytes infiltration was more pronounced in LD group than in LE group on day 7 after treatment, regardless of in the tumor or adjacent liver tissue. Serum cytokines including IL-6, TNF-α and IFN-γ were strongly upregulated in the LD group on day 1 after treatment. And there was no significant difference in the hepatorenal function between LD group and LE group after treatment. The combination of TAE and angiogenesis inhibitor donafenib resulted in a potentiated tumoricidal effect, anti-angiogenesis and antitumour T cell response in rabbit VX2 liver tumor model. This may provide a potential basis for exploring the immune-related mechanisms of embolization in liver cancer.


Embodiment awareness, mathematics discourse, and the blind.
Blindness might be described as a biological condition, and thus remedies could be in the realm of biotechnology. However, the convergence of information technology and cognitive science offers great opportunities for understanding and helping blind children as they learn mathematics, the crosscutting discipline most important for all branches of science and engineering. This article outlines our logic and approach for providing blind students with awareness of the embodiment of their teachers to maintain situated communication. First, we shall show that math discourse is inherently spatiotemporal, and that this information is carried by gesticulation in conjunction with speech. Second, we shall explore the capacity of those who are blind for the imagism necessary for mathematics reasoning. Third, we shall advance a set of augmentative devices suggested by our analysis. Finally, we shall outline our ongoing experiments to validate our rationale.


Effect of concomitant CYP2D6 inhibitor use and tamoxifen adherence on breast cancer recurrence in early-stage breast cancer.
The use of cytochrome P450 2D6-inhibiting drugs (CYP2D6 inhibitors) during tamoxifen treatment leads to a decrease in plasma concentration of endoxifen, the major active tamoxifen metabolite. Concomitant use of CYP2D6 inhibitors, such as selective serotonin reuptake inhibitors, as well as low tamoxifen adherence may negatively impact tamoxifen efficacy in patients with breast cancer. The objectives of this study were to relate concomitant CYP2D6 inhibitor use and tamoxifen adherence to breast cancer event-free time (EFT). Data were from PHARMO and included a community pharmacy dispensing database; PALGA, a nationwide pathology database; and the Dutch Medical Register in the Netherlands. Patients with breast cancer treated with adjuvant tamoxifen between 1994 and 2006 were included. A Cox proportional hazards model with a time-dependent definition for concomitant CYP2D6 inhibitor exposure was used. Adherence calculated over the first year after tamoxifen initiation was related to breast cancer events in the following period. In total, 1,962 patients with breast cancer using tamoxifen were included, among whom 150 (7.6%) frequently used a CYP2D6 inhibitor during tamoxifen treatment. No association between concomitant CYP2D6 inhibitor use and breast cancer recurrence was observed (adjusted hazard ratio [HR], 0.87; 95% CI, 0.42 to 1.79; P = .69). Poor tamoxifen adherence was associated with lower EFT (adjusted HR, 0.987; 95% CI, 0.975 to 0.999; P = .029). This observational study did not show an association between concomitant CYP2D6 inhibitor use and breast cancer recurrence among patients treated with adjuvant tamoxifen despite the strong biologic rationale. This study shows, to the best of our knowledge for the first time, that poor tamoxifen adherence is associated with an increased risk of breast cancer events.


Current status of severe acute respiratory syndrome in China.
Severe acute respiratory syndrome (SARS), also called infectious atypical pneumonia, is an emerging infectious disease caused by a novel variant of coronavirus (SARS-associated coronavirus, SARS-CoV). It is mainly characterized by pulmonary infection with a high infectivity and fatality. SARS is swept across almost all the continents of the globe, and has currently involved 33 countries and regions, including the mainland China, Hong Kong, Taiwan, North America and Europe. On June 30, 2003, an accumulative total reached 8450 cases with 810 deaths. SARS epidemic was very rampant in March, April and May 2003 in the mainland of China and Hong Kong. Chinese scientists and healthcare workers cooperated closely with other scientists from all over the world to fight the disease. On April 16, 2003, World Health Organization (WHO) formally declared that SARS-CoV was an etiological agent of SARS. Currently, there is no specific and effective therapy and prevention method for SARS. The main treatments include corticosteroid therapy, anti-viral agents, anti-infection, mechanical ventilation and isolation. This disease can be prevented and controlled, and it is also curable. Under the endeavor of the Chinese Government, medical staffs and other related professionals, SARS has been under control in China, and Chinese scientists have also made a great contribution to SARS research. Other studies in developing new detection assays and therapies, and discovering new drugs and vaccines are in progress. In this paper, we briefly review the current status of SARS in China.


Efficient sporulation in Clostridium difficile requires disruption of the sigmaK gene.
A 14.6 kb prophage-like insertion, termed skinCd, was found to interrupt the sigK gene, which encodes an RNA polymerase sigma factor essential for sporulation, in six strains of Clostridium difficile. Until now, Bacillus subtilis was the only spore-former shown to carry such an insertion, and the presence of the insertion is not required for efficient sporulation in this organism. The B. subtilis and C. difficile skin elements proved to be divergent in sequence, inserted at different sites within the sigK gene and in opposite orientations. The skinCd element was excised from the chromosome specifically during sporulation, forming a circular molecule. Two natural isolates of C. difficile lacked the skinCd element and were defective in sporulation. When a merodiploid strain was created that carries both interrupted and uninterrupted versions of the sigK gene, the cells became Spo-, showing that the uninterrupted gene is dominant and inhibits sporulation. C. difficile sigK genes, whether skinCd+ or skinCd-, lack the N-terminal pro-sequence found in all other sigK genes studied to date. Thus, regulated excision of skinCd appears to be a critical mechanism for achieving proper temporal activation of sigmaK.


Disparate HDV ribozyme crystal structures represent intermediates on a rugged free-energy landscape.
The hepatitis delta virus (HDV) ribozyme is a member of the class of small, self-cleaving catalytic RNAs found in a wide range of genomes from HDV to human. Both pre- and post-catalysis (precursor and product) crystal structures of the cis-acting genomic HDV ribozyme have been determined. These structures, together with extensive solution probing, have suggested that a significant conformational change accompanies catalysis. A recent crystal structure of a trans-acting precursor, obtained at low pH and by molecular replacement from the previous product conformation, conforms to the product, raising the possibility that it represents an activated conformer past the conformational change. Here, using fluorescence resonance energy transfer (FRET), we discovered that cleavage of this ribozyme at physiological pH is accompanied by a structural lengthening in magnitude comparable to previous trans-acting HDV ribozymes. Conformational heterogeneity observed by FRET in solution appears to have been removed upon crystallization. Analysis of a total of 1.8 µsec of molecular dynamics (MD) simulations showed that the crystallographically unresolved cleavage site conformation is likely correctly modeled after the hammerhead ribozyme, but that crystal contacts and the removal of several 2'-oxygens near the scissile phosphate compromise catalytic in-line fitness. A cis-acting version of the ribozyme exhibits a more dynamic active site, while a G-1 residue upstream of the scissile phosphate favors poor fitness, allowing us to rationalize corresponding changes in catalytic activity. Based on these data, we propose that the available crystal structures of the HDV ribozyme represent intermediates on an overall rugged RNA folding free-energy landscape.


Effects of Aspergillus fumigatus gliotoxin and methylprednisolone on human neutrophils: implications for the pathogenesis of invasive aspergillosis.
Aspergillus fumigatus (AF) is a ubiquitous mold and the most common cause of invasive aspergillosis (IA) in immunocompromised patients. In stem cell transplant recipients, IA now occurs most frequently in the setting of therapy with corticosteroids, including methylprednisolone (MP). We showed previously that gliotoxin (GT), an AF-derived mycotoxin, induces apoptosis in monocytes and dendritic cells, resulting in the suppression of AF-specific T cell responses. We examined the ability of GT to induce apoptosis in polymorphonuclear leukocytes (PMN) and assessed GT effects on important neutrophil functions, including phagocytic function, degranulation, myeloperoxidase activity, and the production of reactive oxygen species (ROS). In contrast to its effects on monocytes, PMN remained resistant to GT-mediated apoptosis. Although many essential neutrophil functions were unaffected, GT inhibited phagocytosis and also induced a decrease in ROS generation by PMN. In contrast, MP therapy potentiated ROS production, suggesting a mechanism that may facilitate tissue injury in IA. Distinct from its effects on untreated PMN, GT augmented ROS production in MP-treated PMN. Our results suggest that although GT may suppress the adaptive immune response, GT may also serve to increase PMN-mediated inflammation, which is likely to play an important role in tissue destruction in the setting of IA.


TNF-α response in macrophages depends on clinical Legionella pneumophila isolates genotypes.
Legionnaires' Disease (LD) is a severe pneumonia mainly caused in Europe by Legionella pneumophila serogroup 1 (Lp1). Sequence-based typing methods reveal that some sequence types (ST) are overrepresented in clinical samples such as ST1 and ST47, suggesting that some strains are more fit for infection than others. In the present study, a collection of 108 Lp1 clinical isolates were used to evaluate the strain-dependent immune responses from human macrophages. Clinical Lp1 isolates induced differential TNFα secretion from macrophages. ST1 isolates induced a significantly higher TNF-α secretion than non-ST1, whereas ST47 isolates induced a significantly lower TNF-α secretion than non-ST47 isolates. ST1 isolates induced a significantly higher cell death than ST47 isolates evaluated by lactate dehydrogenase activity (cytotoxicity) and caspase-3 activity (apoptosis). Treatment of macrophages with anti-TNF-α antibodies significantly reduced the cell death in macrophages infected with ST1 or ST47 strains. The TNF-α secretion was neither explained by a differential bacterial replication nor by the number or type (bystander or infected) of TNF-α producing cells following infection but by a differential response from macrophages. The Paris ST1 reference strain elicited a significantly higher TNF-α gene transcription and a higher induction of NF-κB signaling pathway than the Lorraine ST47 reference strain.Clinical Lp1 isolates induce a diverse immune response and cell death, which could be related to the genotype. The two predominant sequence-types ST1 and ST47 trigger opposite inflammatory response that could be related to the host susceptibility.


A Combination of Aqueous Extraction and Polymeric Membranes as a Sustainable Process for the Recovery of Polyphenols from Olive Mill Solid Wastes.
Polyamide commercial membranes in flat-sheet configuration and with molecular weight cut-off (MWCO) in the range of ultrafiltration (UF) to nanofiltration (NF) were tested for the recovery of phenolic compounds from clarified olive mill solid waste (OMSW) aqueous extracts. The performance of selected membranes was evaluated in terms of productivity (permeate flux) and selectivity towards biologically active compounds (such as phenolic compounds, flavanols, and hydroxycinnamic acids derivatives) and total antioxidant activity (TAA) as a function of transmembrane pressure (TMP). NF membranes produced higher permeate fluxes and a lower fouling index in comparison with UF membranes. Retention of bioactive compounds was also significantly higher for NF membranes than for UF membranes. In particular, membranes with MWCO in the range 150-500 Da showed rejection towards flavanols and hydroxycinnamic acid derivatives of about 100%. On the other hand, the rejection towards TAA and total polyphenols was of about 90% and 72%, respectively. Therefore, NF retentate fractions appear of practical interest for the production of food additives and food supplements due to their high antioxidant activity.


Generation of free oxygen radicals from human polymorphonuclear granulocytes by cytokines from human mononuclear cells, treated with quartz dust DQ12 or coal mine dust TF-1--new aspects in pathogenesis of pneumoconiosis.
We report about the release of a soluble mediator(s) from cultured human monocytes/macrophages after exposure to quartz dust DQ12 or coal mine dust TF-1. This mediator(s) activates isolated human polymorphonuclear granulocytes (PMN) to generation of free oxygen radicals. The strong and long-lasting production of reactive oxygen species (ROS), especially of superoxide anion, was measured as lucigenin dependent chemiluminescence (CL). Studies of mediator exposed PMN with the NBT-test (nitroblue-tetrazolium test) also demonstrated the strong activation of PMN. Electromicroscopical studies of mediator exposed PMN showed strong chemotactic changes in a time dependent manner and suggested the release of lysosomal products. According to these properties we called the mediator(s) "granulocyte activating mediator(s)" (GRAM). Biochemical characterisation indicated a protein nature of GRAM. High pressure liquid chromatography (HPLC) gel-filtration suggested that two molecules or two fragments of one molecule with a m.w. of about 20 kda and just below 10 kda resp. were responsible for the observed effects. PMN are potent inflammatory cells, which are known to immigrate in the lung tissue, especially in the early phases of silicosis. ROS released by activated PMN can act tissue destroying, mutagenic and are probably involved in collagene synthesis by regulation of activity of prolylhydroxylase. Mediator induced release of ROS seems to be an important event in development of lung fibrosis and presents a new mechanism of quartz dust and coal mine dust fibrogenicity.


Systemic lupus erythematosus and pregnancy.
We present a retrospective study of 42 consecutive cases of systemic lupus erythematosus (SLE) and pregnancy followed and delivered during the period 2002-2007 in our department. The mean patient age was 28.6 years and the nulliparity rate was 45.2%. Disease flare up occurred in 9.5% of patients. Lupus anticoagulants, anticardiolipin IgG and IgM antibodies were positive in 33%, 16.6% and 19% of patients, respectively. Mean gestational age at delivery was 36.9 +/- 4.2 and mean birth weight was 2,750 +/- 844 g. Stillbirth, fetal growth restriction, pre-eclampsia and pre-term delivery rates were 7.1%, 14.3%, 2.4% and 23.1%, respectively. Cases with uterine artery Doppler abnormalities had significantly poorer obstetric outcomes. Antiphospholipid antibodies, renal involvement and lupus activation did not have any significant influence on poor obstetric outcome. Multidisciplinary approach to the care of pregnant women with SLE is mandatory for good maternal and fetal outcomes. Uterine artery Doppler seems to be a good prognostic factor for adverse obstetric outcomes.


Increasing the vegetable intake dose is associated with a rise in plasma carotenoids without modifying oxidative stress or inflammation in overweight or obese postmenopausal women.
The optimal amount of vegetable consumption required to reduce chronic disease risk is widely debated. Intervention trials evaluating biological activity of vegetables at various doses are limited. We conducted a 3-dose, crossover feeding trial to test the hypothesis that vegetable intake is associated in a dose-dependent manner with increased plasma carotenoids and subsequently reduced oxidative stress and inflammation in 49 overweight, postmenopausal women. Participants were assigned in random order to 2 (130 g), 5 (287 g), and 10 (614 g) daily servings of fresh, greenhouse-grown vegetables for 3-wk intervals with a 4-wk washout period between treatments. Plasma total carotenoids significantly increased from 1.63 to 2.07 μmol/L with a dose of 2 vegetable servings, from 1.49 to 2.84 μmol/L with a dose of 5 vegetable servings, and from 1.40 to 4.42 μmol/L with a dose of 10 vegetable servings (pre-post paired ttests, all P < 0.001). The change during each feeding period increased with each dose level (P < 0.001). Urine concentrations of 8-isoprostane F2α, hexanoyl lysine, and serum high sensitivity C-reactive protein were not affected by any administered vegetable dose. In this variable-dose vegetable study, a dose-response for plasma carotenoids was demonstrated without significant change in oxidative stress and inflammation in overweight, postmenopausal women.


Spectrum and characteristics of the virus inhibitory action of 2-(alpha-hydroxybenzyl)-benzimidazole.
2-(alpha-Hydroxybenzyl)-benzimidazole (HBB) inhibited the cytopathic effects of the following enteroviruses: polio 1 to 3; Coxsackie A9; Coxsackie B 1 to 6; and ECHO virus types 1 to 9, 11 to 21, and 24 to 27. The following enteroviruses were not inhibited: Coxsackie A types 7, 11, 13, 16, and 18; and ECHO types 22, 23, and 28. Other HBB-insusceptible viruses were: arbor B and C, reo 1 to 3; adeno 2 to 4; influenza B; para-influenza 2 and 3; mumps; herpes simplex, and vaccinia. HBB had no inactivating effect on viral infectivity, but rather inhibited some intracellular step in the reproductive cycle of susceptible viruses. With all viruses examined, inhibition of viral cytopathic effects appeared to be due to inhibition of virus multiplication. Virus inhibition by HBB was demonstrable in monkey kidney, HeLa, and ERK cells. HBB-susceptible viruses varied quantitatively in their susceptibility to the compound, and different strains of the same virus also exhibited varying susceptibility. No relationship was found between attenuation of polioviruses and their susceptibility to the compound. After passage of HBB-susceptible enteroviruses in the presence of the compound, virus populations with lowered susceptibility to HBB were obtained. At virus inhibitory concentrations, HBB did not affect the morphology of cells, nor the following cellular metabolic activities: oxygen uptake; glucose utilization; lactic acid production; and incorporation of adenosine into RNA, and of alanine into proteins. The rates of multiplication of HeLa and ERK. cells were not significantly altered by HBB at virus inhibitory concentrations.


[An AA-amyloidosis course in patients with rheumatoid arthritis].
To characterize renal amyloidosis in patients with rheumatoid arthritis and stages of amyloid nephropathy. The trial covered 30 patients (6 males and 24 females) with documented rheumatoid arthritis (RA) complicated with secondary AA-amyloidosis. Amyloidosis diagnosis was confirmed in all the patients morphologically, the samples were studied with the peroxidase immunohistochemical method using specific monoclonal antibodies to SAA. Clinical manifestations of RA were assessed by the disease activity, functional impairment of the joints, x-ray alterations, extraarticular signs of RA, etc. All the patients were examined clinically, total blood count and biochemical tests were made. In 23 (77%) of 30 examinees with RA, proteinuria as the first clinical symptom of AA-amyloidosis emerged with the first 15 years of RA. RA of the second-third degree of activity were diagnosed in 25 (83%) patients, 21 (70%) patients had apparent destructive changes in the joints (x-ray stage III-IV). Severe functional insufficiency of the joints was observed in 25 (83%) patients, deformation of the joints - in 27 (90%) patients. Clinically, renal amyloidosis was characterized by change of stages - from moderate proteinuria to nephrotic syndrome and renal failure. Prognosis of amyloid nephropathy in RA depends on duration of the proteinuric stage: if this stage is short (3 years maximum), the prognosis is worse than in its long duration. RA ranks first among causes of secondary AA-amyloidosis. Development of AA-amyloidosis in RA patients is most probable in the first 15 years of the course of the articular process. Amyloidosis is more frequent in patients with severe clinical manifestations of RA.


Drivers of woody canopy water content responses to drought in a Mediterranean-type ecosystem.
Severe droughts increase physiological stress in woody plant species, which can lead to mortality, fundamentally altering the composition, structure, and biogeography of forests in many regions. Little is known, however, about the factors determining the physiological response of woody plants to drought at landscape scales. Our objective was to understand woody plant species responses to ongoing changes in climate, using remotely sensed canopy water content (CWC) as an indicator of plant physiological and phenological status. We used fused imaging spectroscopy and light detection and ranging from the Carnegie Airborne Observatory to quantify the factors affecting species compositional changes in CWC in a diverse Mediterranean-type ecosystem (Jasper Ridge Biological Preserve, California, USA) between 2013 and 2015. Mapped CWC was spatially variable in both of the observation years, and proved to be most closely tied to species composition and distribution across the landscape. The secondary predictors of CWC were elevation and soil substrate. In contrast, we found that CWC change was much more related to environmental factors than to the species composition. We suggest that the effect of environment on CWC change is mediated through species resistance and resilience to drought. Monitoring CWC change with imaging spectroscopy is a powerful approach to identifying species-level responses to climatic events and long-term change, which may provide support for policy decisions and conservation at large spatial scales.


The Effect of BMI and Gender on Bleeding Events when Rivaroxaban Is Administered for Thromboprophylaxis Following Total Hip and Total Knee Arthroplasty.
Rivaroxaban is approved in Europe and the United States for thromboprophylaxis following total joint arthroplasty. As the rate of obesity increases, confirming safety and efficacy in this patient population is paramount. This retrospective chart review assessed the efficacy and safety of rivaroxaban between two body mass index (BMI) groups: normal or overweight (< 30 kg/m2) and obese or morbidly obese (≥30 kg/m2). Safety outcome was a major bleeding event, defined as a decrease in hemoglobin of at least 2 g/dL from postoperative day 1(POD 1) to discharge or a blood transfusion of at least two units. Efficacy outcome was venous thromboembolism within 35 days postoperatively. There were 68 (68/1,241; 5.48%) major bleeding events. There was no significant association between major bleeding events and BMI in the univariable analysis (p < 0.36). However, after adjusting for other factors in the multivariable model, there was a significant interaction between BMI and gender (p < 0.001). Among males, the incidence of major bleeding events was three times greater in obese/morbidly obese subjects as compared with normal/overweight male subjects (odds ratio [OR]: 3.09, 95% confidence interval [CI]: 1.25, 7.62). Among females, incidence of having a major bleeding event was almost two times greater in normal/overweight subjects as compared with obese/morbidly obese female subjects (OR: 2.17, 95% CI: 1.10, 4.35). Incidence of venous thromboembolism was 0.4% in each group. The authors' study results highlight a previously unexplored association between BMI and gender-dependent differences in bleeding outcomes when rivaroxaban is used for thromboprophylaxis following total joint arthroplasty.


UL146 variability among clinical isolates of human cytomegalovirus from Japan.
Human cytomegalovirus (HCMV) is a herpesvirus associated with serious diseases in immunocompromised subjects. The region between ORF UL133 and UL151 from HCMV, named ULb' is frequently deleted in attenuated AD169 and in highly passaged laboratory strains. However, this region is conserved in low-passaged and more virulent HCMV, like the Toledo strain. The UL146 gene, which is located in the ULb' region, encodes a CXC-chemokine analogue. The diversity of UL146 gene was evaluated among fifty-six clinical isolates of HCMV from Japan. Results show that UL146 gene was successfully amplified by the polymerase chain reaction (PCR) in only 17/56 strains (30%), while the success rate for UL145/UL147 gene was 18/56 strains (32%). After DNA sequencing, the 35 amplified strains were classified into 8 groups. When compared, variability of UL146 ranged from 25.1% to 52.9% at the DNA level and from 34.5% to 67% at the amino acid level. Seven groups had the interleukin-8 (IL-8) motif ERL (Glu-Leu-Arg) CXC and one group had only the CXC motif, suggesting the absence of the IL-8 function of UL146. In conclusion, we found that UL146 gene of HCMV is hyper-variable in clinical strains from Japan suggesting the possibility of a different function in each sequence group.


Electronic Tongue for Direct Assessment of SARS-CoV-2-Free and Infected Human Saliva-A Feasibility Study.
An electronic tongue is a powerful analytical instrument based on an array of non-selective chemical sensors with a partial specificity for data gathering and advanced pattern recognition methods for data analysis. Connecting electronic tongues with electrochemical techniques for data collection has led to various applications, mostly within sensing for food quality and environmental monitoring, but also in biomedical research for the analyses of different bioanalytes in human physiological fluids. In this paper, an electronic tongue consisting of six electrodes (viz., gold, platinum, palladium, titanium, iridium, and glassy carbon) was designed and tested in authentic (undiluted, unpretreated) human saliva samples from eight volunteers, collected before and during the COVID-19 pandemic. Investigations of 11 samples using differential pulse voltammetry and a principal component analysis allowed us to distinguish between SARS-CoV-2-free and infected authentic human saliva. This work, as a proof-of-principle demonstration, provides a new perspective for the use of electronic tongues in the field of enzyme-free electrochemical biosensing, highlighting their potential for future applications in non-invasive biomedical analyses.


Analysis of expression profiling data suggests explanation for difficulties in finding biomarkers for nasal polyps.
Identification of clinically useful biomarkers for Nasal Polyposis in chronic rhinosinusitis (CRSwNP) has proven dif-ficult. We analyzed gene expression profiling data to find explanations for this. We analyzed mRNA expression profiling data, GSE36830, of six uncinate tissues from healthy controls and six NP from CRSwNP patients. We performed Ingenuity Pathway Analysis (IPA) of differentially expressed genes to identify pathways and predicted upstream regulators. We identified 1,608 differentially expressed genes and 177 significant pathways, of which Th1 and Th2 activation pathway and leukocyte extravasation signaling were most significant. We identified 75 upstream regulators whose activity was predicted to be upregulated. These included regulators of known pathogenic and therapeutic relevance, like IL-4. However, only seven of the 75 regulators were actually differentially expressed in NP, namely CSF1, TYROBP, CCL2, CCL11, SELP, ADORA3, ICAM1. Interes-tingly, these did not include IL-4, and four of the seven were receptors. This suggested a potential explanation for the discrepancy between the predicted and observed expression levels of the regulators, namely that the receptors, and not their ligands, were upregulated. Indeed, we found that 10 receptors of key predicted upstream regulators were upregulated, including IL4R. Our findings indicate that the difficulties in finding specific biomarkers for CRSwNP depend on the complex underly-ing mechanisms, which include multiple pathways and regulators, each of which may be subdivided into multiple components such as ligands, soluble and membrane-bound receptors. This suggests that combinations of biomarkers may be needed for CRSwNP diagnostics.


A Study on Dosimetric Outcomes and Acute Toxicity of Post Mastectomy Adjuvant Hypofractionated Radiotherapy for Breast Cancer.
Hypofractionated External Beam Radiotherapy (HFRT) is a relatively new adjuvant Radiotherapy (RT) schedule for breast cancers following breast conservation surgery and less commonly, following mastectomy. Here we report our experience on normal tissue exposure and acute toxicity of HFRT after mastectomy. To assess the dosimetric outcomes and acute toxicity profile of adjuvant HFRT following mastectomy for breast cancer. This prospective observational study considered consecutive patients planned for adjuvant HFRT (42.5 Gy in 16 sessions delivered over 3 weeks) to the chest wall with/without regional nodes between October 2014 and June 2015. The dosimetric parameters including dose homogeneity to the target volume and exposure to heart and lung were analyzed. Acute haematological and dermatological toxicity was recorded until upto three months after completion of RT. Among the 56 patients treated with HFRT, the mean age was 49 years (range: 28-69 years). Pathologically positive nodes and ≥pT3 primary was observed in 44 (78.6%) and 12 (21.4%) patients, respectively. Majority (87.5%) received prior adjunct chemotherapy. RT to the supraclavicular fossa was delivered for 39 (69.6%) patients. The mean V90 and V95 to the Planning Target Volume (PTV) were 95% (± 3.3%) and 93% (± 4%), respectively. The maximum dose received was on average 47.7 Gy (112%; range: 46.2-48.5 Gy). The mean lung dose was 10.2 Gy (± 3.5 Gy) and V20 was 20.9% (± 6%). The mean V25 to heart was 6.6% (± 4.8%) for left sided and 0% for right sided tumours (p=0.001). Acute skin toxicity peaked at completion of RT and was tolerable (grade 0, I, II and III reactions were 75%, 16% and 1.8%, respectively). No patient had ≥ grade III haematological toxicity, and treatment was not interrupted for any patient. Adjuvant HFRT could be planned while meeting the dose constraints to normal tissues in all patients and was well tolerated, with mild to moderate acute adverse effects that did not warrant any therapeutic intervention or treatment interruption.


Modulation of neurotransmitter release by carbon monoxide at the frog neuro-muscular junction.
Carbon monoxide (CO) is an endogenous gaseous messenger, which regulates numerous physiological functions in a wide variety of tissues. Using extracellular microelectrode recording from frog neuro-muscular preparation the mechanisms of exogenous and endogenous CO action on evoked quantal acetyl-choline (Ach) release were studied. It was shown that CO application increases Ach-release in dose-dependent manner without changes in pre-synaptic Na+ and K+ currents. The effect of exogenous CO on Ach-release was decreased by prior application of guanylate cyclase inhibitor ODQ and prevented by application of a cyclic guanylate monophosphate (cGMP) analog 8Br-cGMP. Pre-treatment of the preparation with adenylate cyclase inhibitor MDL-12330A has completely abolished the effect of CO, whereas elevation of intracellular level of cyclic adenosine monophosphate (cAMP) mimicked and eliminated CO action. Application of cGMP-activated phosphodiesterase-2 inhibitor EHNA did not prevent CO action, whereas inhibition of cGMP-inhibited phosphodiesterase-3 by quazinone has partially blocked the effect of CO. Utilizing immuno-histochemical methods CO-producing enzyme heme-oxygenase-2 (HO-2) was shown to be expressed in skeletal muscle fibers, mostly in sub-sarcolemmal region, karyolemma and sarcoplasmic reticulum. Zn-protoporphirin-IX, the selective HO-2 blocker, has depressed Ach-release, suggesting the tonic activating effect of endogenous CO on pre-synaptic function. These results suggest that facilitatory effect of CO on Ach-release is mediated by elevation of intracellular cAMP level due to activation of adenylate cyclase and decrease of cAMP breakdown. As such, endogenous skeletal muscle-derived CO mediates tonic retrograde up-regulation of neuro-transmitter release at the frog neuro-muscular junction.


SMART Recovery International and COVID-19: Expanding the reach of mutual support through online groups.
Mutual support groups play an extremely important role in providing opportunities for people to engage in alcohol and other drug (AOD) treatment and support. SMART Recovery groups employ cognitive, behavioural and motivational principles and strategies to offer support for a range of addictive behaviours. COVID-19 fundamentally changed the way that these groups could be delivered. A series of online meetings were conducted by the lead author (PK) and the SMART Recovery International Executive Officer (KM), with representatives from the SMART Recovery National Offices in the Ireland (DO), United States (MR), Australia (RM), and Denmark (BSH, DA), and the United Kingdom (AK). The meetings focused on discussing the impacts of COVID-19 on SMART Recovery in each of the regions. As a result of restrictions to prevent the transmission of COVID-19, the vast majority of SMART Recovery face-to-face meetings were required to cease globally. To ensure people still had access to AOD mutual support, SMART Recovery rapidly scaled up the provision of online groups. This upscaling has increased the number of groups in countries that had previously provided a limited number of online meetings (i.e., United States, England, Australia), and has meant that online groups are available for the first time in Denmark, Ireland, Hong Kong, Spain, Malaysia and Brazil. Whilst the urgent and rapid expansion of online groups was required to support people during the pandemic, it has also created an opportunity for the ongoing availability of online mutual support post-pandemic. The challenge for the research community is to critically evaluate the online delivery of mutual support groups, to better understand the mechanisms through which they may work, and to help understand the experience of people accessing the groups.


Meta-Analysis of the Impact of the Learning Curve in Robotic Rectal Cancer Surgery on Histopathologic Outcomes.
Although the process of learning robotic surgery for rectal cancer is associated with a prolonged operating time and higher complication rates, its impact on histopathologic outcomes is unknown. The aim of this meta-analysis was to evaluate the impact of the learning curve in robotic surgery for rectal cancer on histopathologic outcomes. The PubMed, EMBASE, Cochrane Library, MEDLINE via Ovid, CINAHL, and Web of Science databases were systematically searched. The inclusion criterion was any clinical study comparing the outcomes of robotic surgery for rectal cancer between different phases of the learning curve (LC) including competence (C). The primary endpoint was the circumferential resection margin (CRM) involvement rate defined as CRM ≤1 mm. The Mantel-Haenszel method with odds ratios with 95% confidence intervals (OR (95%CI)) was used for dichotomous variables. Ten studies including a total of 907 patients (521 LC and 386 C) were selected. Nine studies were found to have a low risk of bias, and one had a moderate risk of bias. The CRM involvement rate was 2.9% (13/441) for learning curve vs. 4.6% (13/284) for competence. This difference was not significant (OR (95%CI) = 0.70 (0.30, 1.60); p=0.39; I2=0%). A surgeon's learning curve seems to have no impact on CRM involvement rates compared to surgeon competence in robotic surgery for rectal cancer.


Extrapulmonary inflammatory myofibroblastic tumor: a clinical and pathological survey.
Inflammatory myofibroblastic tumor (IMT) or inflammatory pseudotumor was initially recognized in the lung, and somewhat later, a similar-appearing pathological process was reported in the liver. Presently, this tumor has been described in virtually all major organs and extrapulmonary sites with a few exceptions. It was thought initially that the IMT was nonneoplastic and represented an aberrant inflammatory response despite its gross and microscopic features of a spindle cell neoplasm. The inflammatory hypothesis about the pathogenesis has been more readily accommodated in the lung than in the extrapulmonary sites of involvement. Some cases, however, were accompanied by the constitutional symptoms and signs of an inflammatory process, which resolved in most cases after surgical resection. There were some pathological aspects of the IMT that seemingly contradicted its purely inflammatory nature, including its potential for local recurrence; development of multifocal, noncontiguous tumors; infiltrative local growth; vascular invasion; and malignant transformation. These pathological features seemed to support the hypothesis that the IMT is a neoplastic process, which has been augmented by reports that these tumors have clonal characteristics. Other studies have suggested that IMTs of the liver and spleen are associated with the Epstein-Barr virus. From the diagnostic perspective, there are several potential difficulties that the pathologist may encounter in the examination of one of these tumors. Just as it was true 60 years ago, the potential for a pathological diagnosis of one or another type of spindle cell sarcoma has not diminished with time. Because these tumors have a predilection for children, embryonal rhabdomyosarcoma is another diagnostic temptation when an IMT presents in the bladder or other hollow viscus. The IMT should probably be regarded as a soft tissue-mesenchymal tumor with an indeterminant or low malignant potential, which is a somewhat indefinite but realistic prognostic category.


Patellar ligament rupture in the cat: repair methods and patient outcomes in seven cases.
The medical records of cats receiving surgical treatment for unilateral patellar ligament rupture between 1999 and 2012 at 12 referral centres in the UK and Ireland were reviewed. Seven cases were identified: six were caused by trauma and one was iatrogenic, occurring as a complication following surgical stabilisation of a tibial fracture. All cases were treated by sutured anastomosis of the ruptured ligament, with six of the repairs protected by a circumpatellar and/or transpatellar loop of suture. The stifle was immobilised by transarticular external skeletal fixation in three cases. No cases required revision surgery. No complications were reported. Final evaluation, performed at a median time of 31 days, determined five patients to have returned to acceptable or good limb function; two cases were lost to follow-up. The data suggest that, in cats, the current surgical techniques extrapolated from their canine counterparts for repair of a completely or partially ruptured patellar ligament are successfully used and result in acceptable limb function.


What's new in chronic inflammatory demyelinating polyradiculoneuropathy in 2007-2008?
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)-related research has made progress in the field of pathogenesis, genetics, and treatment. The number of circulating CD4(+) CD25(+) T-regulatory cells was shown to be reduced in CIDP patients. Increased frequency of genotype GA13-16 of the SH2D2A gene encoding for a T-cell-specific adapter protein in CIDP patients may result in a defective control and elimination of autoreactive T cells. IVIg treatment has been shown to increase numbers and function of peripheral CD4(+) CD25(+) T-regulatory cell in a mouse model. These findings shed new light on the understanding of why peripheral tolerance is breached in CIDP patients and why the disease becomes chronic and adds another possible mechanism of action of intravenous immunoglobulin to the already long list. Long-term effectiveness of IVIg has now been proven. Subcutaneous immunoglobulin could be an alternative for IVIg, but this has to be explored further in well-designed trials. Autologous stem cell transplantation has been tried in refractory patients, but larger trials are necessary to assess safety and effect of this treatment.


Sound wave propagation on the human skull surface with bone conduction stimulation.
Bone conduction (BC) is an alternative to air conduction to stimulate the inner ear. In general, the stimulation for BC occurs on a specific location directly on the skull bone or through the skin covering the skull bone. The stimulation propagates to the ipsilateral and contralateral cochlea, mainly via the skull bone and possibly via other skull contents. This study aims to investigate the wave propagation on the surface of the skull bone during BC stimulation at the forehead and at ipsilateral mastoid. Measurements were performed in five human cadaveric whole heads. The electro-magnetic transducer from a BCHA (bone conducting hearing aid), a Baha® Cordelle II transducer in particular, was attached to a percutaneously implanted screw or positioned with a 5-Newton steel headband at the mastoid and forehead. The Baha transducer was driven directly with single tone signals in the frequency range of 0.25-8 kHz, while skull bone vibrations were measured at multiple points on the skull using a scanning laser Doppler vibrometer (SLDV) system and a 3D LDV system. The 3D velocity components, defined by the 3D LDV measurement coordinate system, have been transformed into tangent (in-plane) and normal (out-of-plane) components in a local intrinsic coordinate system at each measurement point, which is based on the cadaver head's shape, estimated by the spatial locations of all measurement points. Rigid-body-like motion was dominant at low frequencies below 1 kHz, and clear transverse traveling waves were observed at high frequencies above 2 kHz for both measurement systems. The surface waves propagation speeds were approximately 450 m/s at 8 kHz, corresponding trans-cranial time interval of 0.4 ms. The 3D velocity measurements confirmed the complex space and frequency dependent response of the cadaver heads indicated by the 1D data from the SLDV system. Comparison between the tangent and normal motion components, extracted by transforming the 3D velocity components into a local coordinate system, indicates that the normal component, with spatially varying phase, is dominant above 2 kHz, consistent with local bending vibration modes and traveling surface waves. Both SLDV and 3D LDV data indicate that sound transmission in the skull bone causes rigid-body-like motion at low frequencies whereas transverse deformations and travelling waves were observed above 2 kHz, with propagation speeds of approximately of 450 m/s at 8 kHz.


Short CAG repeats within the hSKCa3 gene associated with schizophrenia: results of a family-based study.
In a family-based association study we investigated transmission of a multiallelic CAG repeat in a novel neuronal potassium channel gene, hSKCa3, in 59 parent/ offspring trios. In contrast to recent reports of an association of moderately large repeats with schizophrenia in case-control studies, our findings indicate that short CAG repeats (< or=19 repeats) are transmitted at an increased frequency to schizophrenic offspring (p=0.014), particularly among familial cases (p=0.007). No evidence for a parent-of-origin effect was found. Multiallelic TDT procedure showed no association of individual CAG repeats to schizophrenia. Further studies using family-based designs should clarify whether hSKCa3 is a susceptibility factor to schizophrenia or co-segregates with a major disease gene in tight linkage.


Changes of serum omentin-1 levels and relationship between omentin-1 and insulin resistance in chronic hepatitis C patients.
Omentin-1 is a novel adipokine that has a pivotal role in modulating the insulin sensitivity, immunity and inflammation. The current study was conducted to evaluate the serum omentin-1 level in hepatitis C virus (HCV) infected patients, with or without type 2 diabetes, and to investigate its correlation with liver function parameters and insulin resistance. Eighty subjects were enrolled in this study divided into four groups: chronic HCV infected patients (n=20), chronic hepatitis C patients with concomitant type 2 diabetes (n=18), type 2 diabetic patients (n=22) and 20 healthy controls. Serum omentin-1 levels were assessed using enzyme-linked immunosorbent assay (ELISA). Fasting blood glucose, insulin levels, and liver parameters including aminotransferases (ALT and AST) were determined. Serum omentin-1 levels were significantly elevated in HCV infected patients compared to all other groups. Omentin-1 levels were positively correlated with AST and ALT levels (r =0.43, p< 0.001; r =0.423, p<0.001, respectively). Additionally, a significant negative correlation was found between omentin-1 and both fasting insulin levels and homeostasis model assessment of insulin resistance (HOMA-IR) (r = -0.238, p<0.05; r = -0.277, p<0.05, respectively). Furthermore, fasting blood glucose, HbA1c and HOMA-β were negatively correlated to serum omentin-1 levels however these correlations were not statistically significant. Serum omentin-1 level is elevated in HCV infected patients and is positively associated with liver enzymes AST and ALT. This suggested that omentin-1 may be implicated in the pathogenesis of hepatitis C and its metabolic complications. However its role needs to be elucidated by further studies.


Baclofen in trigeminal neuralgia: its effect on the spinal trigeminal nucleus: a pilot study.
Experiments with cats showed that baclofen resembles carbamazepine and phenytoin sodium in its ability to depress excitatory synaptic transmission in the spinal trigeminal nucleus. Baclofen was, therefore, given to 14 patients with refractory trigeminal neuralgia. Ten patients were relieved of the paroxysms of tic douloureux while taking 60 to 80 mg/day of baclofen. A reduction in the dosage of baclofen in six of these patients resulted in a recurrence of painful paroxysms in five patients. Seven patients have been pain-free or almost pain-free on a regimen of baclofen for four to 12 months. Our results suggest that baclofen may be a useful drug in the treatment of trigeminal neuralgia and that our experimental model may successfully predict the efficacy of a drug in the treatment of this condition.


Selective Disruption of the Blood-Brain Barrier by Zika Virus.
The blood-brain barrier (BBB) selectively regulates the cellular exchange of macromolecules between the circulation and the central nervous system (CNS). Here, we hypothesize that Zika virus (ZIKV) infects the brain via a disrupted BBB and altered expression of tight junction (TJ) proteins, which are structural components of the BBB. To assess this hypothesis, in vitro and in vivo studies were performed using three different strains of ZIKV: Honduras (ZIKV-H), Puerto Rico (ZIKV-PR), and Uganda (ZIKV-U). Primary human brain microvascular endothelial cells (BMECs) were productively infected by all studied ZIKV strains at MOI 0.01, and were analyzed by plaque assay, immunofluorescence for NS1 protein, and qRT-PCR at 2 and 6 days post-infection (dpi). Compared to mock-infected controls, expression level of ZO-1 was significantly upregulated in ZIKV-H-infected BMECs, while occludin and claudin-5 levels were significantly downregulated in BMECs infected by all three studied viral strains. Interestingly, BMEC permeability was not disturbed by ZIKV infection, even in the presence of a very high viral load (MOI 10). All studied ZIKV strains productively infected wild-type C57BL/J mice after intravenous infection with 107 PFU. Viral load was detected in the plasma, spleen, and brain from 1 to 8 dpi. Peak brain infection was observed at 2 dpi; therefore, TJ protein expression was assessed at this time point. Claudin-5 was significantly downregulated in ZIKV-U-infected animals and the BBB integrity was significantly disturbed in ZIKV-H-infected animals. Our results suggest that ZIKV penetrates the brain parenchyma early after infection with concurrent alterations of TJ protein expression and disruption of the BBB permeability in a strain-dependent manner.


Nanosized Calcium Phosphates as Novel Macronutrient Nano-Fertilizers.
The need for qualitatively and quantitatively enhanced food production, necessary for feeding a progressively increasing World population, requires the adoption of new and sustainable agricultural protocols. Among them, limiting the waste of fertilizers in the environment has become a global target. Nanotechnology can offer the possibility of designing and preparing novel materials alternative to conventional fertilizers, which are more readily absorbed by plant roots and, therefore, enhance nutrient use efficiency. In this context, during the last decade, great attention has been paid to calcium phosphate nanoparticles (CaP), particularly nanocrystalline apatite and amorphous calcium phosphate, as potential macronutrient nano-fertilizers with superior nutrient-use efficiency to their conventional counterparts. Their inherent content in macronutrients, like phosphorus, and gradual solubility in water have been exploited for their use as slow P-nano-fertilizers. Likewise, their large (specific) surfaces, due to their nanometric size, have been functionalized with additional macronutrient-containing species, like urea or nitrate, to generate N-nano-fertilizers with more advantageous nitrogen-releasing profiles. In this regard, several studies report encouraging results on the superior nutrient use efficiency showed by CaP nano-fertilizers in several crops than their conventional counterparts. Based on this, the advances of this topic are reviewed here and critically discussed, with special emphasis on the preparation and characterization approaches employed to synthesize/functionalize the engineered nanoparticles, as well as on their fertilization properties in different crops and in different (soil, foliar, fertigation and hydroponic) conditions. In addition, the remaining challenges in progress toward the real application of CaP as nano-fertilizers, involving several fields (i.e., agronomic or material science sectors), are identified and discussed.


Combined perventricular septal defect closure and patent ductus arteriosus ligation via the lower ministernotomy approach.
Over the past decade, minimally invasive approaches have been advocated for surgical correction of congenital defects to reduce costs related to hospitalization and for improved cosmesis. Minimal skin incisions and partial sternotomy reduce surgical trauma, however these techniques might not be successful in treating a number of congenital pathological conditions, particularly for combined congenital defects. We focused on cases with a combined presentation of ventricular septal defect and patent ductus arteriosus. We studied 12 infants who successfully underwent surgical treatment for a combined single-stage ventricular septal defect and patent ductus arteriosus closure through a lower ministernotomy without using cardiopulmonary bypass and X-rays. No intraoperative and early postoperative complications or mortality were noted. Postoperative echocardiography did not reveal residual shunts. The proposed technique is safe and reproducible in infants.


Transport calculations of depth-dose distributions for gadolinium neutron capture therapy.
Depth-dose distributions were calculated for thermal and epithermal neutron fluence and capture gamma ray dose rates using a two-dimensional neutron-coupled gamma-ray transport code (DOT 3.5) for gadolinium neutron capture therapy. The results show that (i) a capture gamma-ray dose rate of 10 Gy h-1 was obtained with a thermal neutron fluence rate of 1.5 x 10(9) cm-2 s-1 in a simulated tumour containing 5000 PPM gadolinium placed near the surface of a water phantom, (ii) deep-seated tumours may be treated with epithermal neutrons, and (iii) gadolinium neutron capture therapy appears to achieve comparable dose distributions to those of boron neutron capture therapy.


A small molecule inhibitor of beta-catenin/CREB-binding protein transcription [corrected].
Inherited and somatic mutations in the adenomatous polyposis coli occur in most colon cancers, leading to activation of beta-catenin-responsive genes. To identify small molecule antagonists of this pathway, we challenged transformed colorectal cells with a secondary structure-templated chemical library, looking for compounds that inhibit a beta-catenin-responsive reporter. We identified ICG-001, a small molecule that down-regulates beta-catenin/T cell factor signaling by specifically binding to cyclic AMP response element-binding protein. ICG-001 selectively induces apoptosis in transformed cells but not in normal colon cells, reduces in vitro growth of colon carcinoma cells, and is efficacious in the Min mouse and nude mouse xenograft models of colon cancer.


Discovery of putative small non-coding RNAs from the obligate intracellular bacterium Wolbachia pipientis.
Wolbachia pipientis is an endosymbiotic bacterium that induces a wide range of effects in its insect hosts, including manipulation of reproduction and protection against pathogens. Little is known of the molecular mechanisms underlying the insect-Wolbachia interaction, though it is likely to be mediated via the secretion of proteins or other factors. There is an increasing amount of evidence that bacteria regulate many cellular processes, including secretion of virulence factors, using small non-coding RNAs (sRNAs), but sRNAs have not previously been described from Wolbachia. We have used two independent approaches, one based on comparative genomics and the other using RNA-Seq data generated for gene expression studies, to identify candidate sRNAs in Wolbachia. We experimentally characterized the expression of one of these candidates in four Wolbachia strains, and showed that it is differentially regulated in different host tissues and sexes. Given the roles played by sRNAs in other host-associated bacteria, the conservation of the candidate sRNAs between different Wolbachia strains, and the sex- and tissue-specific differential regulation we have identified, we hypothesise that sRNAs may play a significant role in the biology of Wolbachia, and in particular in its interactions with its host.


Rehabilitation of Auricular Defect with Implant-Retained Auricular Prosthesis - A Case Report.
Maxillofacial defect is of great concern physically, emotionally, and psychologically for a patient. However, it is an even bigger challenge for a team attempting rehabilitation, as a crucial decision has to be made between surgical approach and/or prosthetic rehabilitation. However, if both are combined, it will result in best of esthetics and function with ease of maintainance, resulting in a sucessful rehabilitation. This case report represents a case of auricular defect rehabilitated with a combination of implants and bar-retained silicone prosthesis. A 38-year-old male patient with right auricular defect reported with the main concern of esthetic rehabilitation of a lost part of the external ear. With through evaluation and examination, a diagnosis of acquired partial auricular defect of the right side secondary to trauma was established. An implant-retained auricular prosthesis was planned for this case. Surgically, three intraoral implants were placed in the mastoid bone, and after healing, bar framework was fabricated and attached. Finally, silicone prosthesis was fabricated and delivered to the patient. A successful rehabilitation was carried out in this case using implants and bar attachment for retention of the silicone prosthesis. This prosthesis provided excellent retention and restored the appearance and confidence of the patient. Rehabilitation of the auricular defect can be carried out with surgical approach, which involves multiple surgeries, and still, the results may not be esthetically favorable. Prosthetic rehabilitation is an option, but retention is generally a hindrance. However, implant-retained prosthesis has really paved a way for rehabilitation of the maxillofacial defect esthetically and more reliably. Cone-beam computerized tomography (CT) can be used for planning and evaluation instead of CT, which will save the patient from a lot of radiation exposure. Hence, in the maxillofacial defect, attempts should be made to explore the option of implant-retained prosthesis.


Quality of the interface of primary tooth dentin bonded with antibacterial fluoride-releasing adhesive.
Limited information is available on the physical properties and ultrastructure of resin-dentin interfaces created in primary teeth. The interfacial quality of sound and caries-affected primary tooth dentin bonded with an antibacterial fluoride-releasing self-etch adhesive was examined in the present study. Primary molars were bonded with Clearfil Protect Bond (Kuraray Medical). A nano-indentation tester was employed for creating indentations vertically across resin-dentin interfaces of the bonded sound and caries-affected primary dentin for determination of hardness (H) and Young's modulus (Y). Statistical analysis were performed using one-way and two-way ANOVA and Fisher's PLSD test at p<0.05. Similar resin-dentin interfaces were examined with SEM/EDX, and with TEM using ammoniacal silver nitrate tracer for nanoleakage. In both sound and caries-affected dentin, compared to the underlying dentin, significantly lower values were seen in the H and Y values of the interfacial dentin except for the H in caries-affected dentin. No significant difference between the interfacial dentin and the underlying dentin was observed in the H of caries-affected dentin and the Ca and P contents in both sound and caries-affected dentin. TEM revealed extensive interfacial nanoleakage in bonded sound dentin, while no silver deposit in bonded caries-affected dentin. However, silver deposits were observed in the porous caries-affected dentin beneath the interface. Within the limitation of this study, Clearfil Protect Bond cannot demonstrate evidence of remineralization, does not increase the hardness and elasticity of the interfacial dentin, and does not prevent nanoleakage along the resin-dentin interface.


[The use of monoclonal antibodies with human IgE for determining the level of allergen-specific IgE].
The possibility of using monoclonal antibodies to human IgE, obtained in our laboratory, with the aim to determine allergen-specific IgE in the radioallergosorbent test (RAST), the enzyme immunoassay and the radioimmunoassay has been studied. The results obtained with the use of the standard RAST system (manufactured by Pharmacia, Sweden) and different variants of assay based on the use of our antibodies, labeled with 125I or conjugated with peroxidase, and timothy pollen allergen (obtained from the Stavropol Research Institute for Vaccines and Sera) have been compared. The best results have been obtained with anti-IgE antibodies 11-2, but for working out our assay systems it is necessary to develop our own standards and control limits.


Dose response effect of conjugated equine oestrogen on blood pressure in postmenopausal women with hypertension.
This study was designed to compare with placebo the dose-response of conjugated equine oestrogen (CEE) on blood pressure in hypertensive postmenopausal women. Fourteen postmenopausal women with grade 1-2 hypertension participated in the study which used a double-blind crossover design. There were four randomised treatment phases, each lasting 4 weeks. The four treatments were CEE 0.3 mg, CEE 0.625 mg, CEE 1.25 mg and placebo. Each subject also received non-blinded medroxyprogesterone acetate (MPA) 10 mg for the final 14 days of each 28-day treatment cycle. Clinic blood pressure was measured weekly with the mean values of weeks 3 and 4 of each phase used for analysis. Ambulatory blood pressure was performed in week 4 of each phase. Compared with placebo, clinic systolic blood pressure was reduced in the CEE 0.3 mg and CEE 0.625 mg phases (p < 0.05) and clinic diastolic blood pressure was reduced in the CEE 0.625 mg phase (p < 0.05). There was no significant effect of CEE on ambulatory blood pressure, although the blood pressure pattern was similar to clinic measurements. In hypertensive postmenopausal women, daily CEE together with cyclical MPA has a variable effect on blood pressure depending on CEE dose. The "lower" and "middle" doses of CEE produced a small reduction in blood pressure which reached a nadir and tended to reverse with the "higher" CEE dose.


Experimental Evidence for Quantum Tunneling Time.
The first hundred attoseconds of the electron dynamics during strong field tunneling ionization are investigated. We quantify theoretically how the electron's classical trajectories in the continuum emerge from the tunneling process and test the results with those achieved in parallel from attoclock measurements. An especially high sensitivity on the tunneling barrier is accomplished here by comparing the momentum distributions of two atomic species of slightly deviating atomic potentials (argon and krypton) being ionized under absolutely identical conditions with near-infrared laser pulses (1300 nm). The agreement between experiment and theory provides clear evidence for a nonzero tunneling time delay and a nonvanishing longitudinal momentum of the electron at the "tunnel exit."


Bacterial community structure in the drinking water microbiome is governed by filtration processes.
The bacterial community structure of a drinking water microbiome was characterized over three seasons using 16S rRNA gene based pyrosequencing of samples obtained from source water (a mix of a groundwater and a surface water), different points in a drinking water plant operated to treat this source water, and in the associated drinking water distribution system. Even though the source water was shown to seed the drinking water microbiome, treatment process operations limit the source water's influence on the distribution system bacterial community. Rather, in this plant, filtration by dual media rapid sand filters played a primary role in shaping the distribution system bacterial community over seasonal time scales as the filters harbored a stable bacterial community that seeded the water treatment processes past filtration. Bacterial taxa that colonized the filter and sloughed off in the filter effluent were able to persist in the distribution system despite disinfection of finished water by chloramination and filter backwashing with chloraminated backwash water. Thus, filter colonization presents a possible ecological survival strategy for bacterial communities in drinking water systems, which presents an opportunity to control the drinking water microbiome by manipulating the filter microbial community. Grouping bacterial taxa based on their association with the filter helped to elucidate relationships between the abundance of bacterial groups and water quality parameters and showed that pH was the strongest regulator of the bacterial community in the sampled drinking water system.


Intimal Flaps Detected by Optical Frequency Domain Imaging in the Proximal Segments of Native Coronary Arteries.
Background: The prevalence and clinical sequelae of optical frequency domain imaging (OFDI)-detected intimal flaps caused by vessel trauma or plaque rupture in the proximal native coronary arteries have not been described. Methods and Results: OFDI investigation was performed following stent implantation in patients with ST-segment elevation myocardial infarction (STEMI). We defined a flap-like structure (FS) as a disruption or discontinuation of the endoluminal vessel surface, and classified as actual flap or artifact. FS in the left main stem, or maximally 20mm distal to the guiding catheter in the proximal right coronary artery were assessed. A total of 8,931 frames in 97 patients were analyzed in a frame-by-frame fashion (0.125-mm interval). OFDI identified 8 FS in 7 patients, none of which was evident angiographically. All FS were left untreated because the operators per protocol were blinded to the OFDI images. A total of 5 FS in 5 patients (5.1%) appeared to be actual flaps in which only the intima was involved (mean distance from guiding catheter: 4.8±2.7mm). The remaining 3 FS in 3 patients were artifacts; namely, residual blood and interface light reflectivity. There were no adverse cardiac events during 6-months follow-up. Conclusions: In 5.1% of STEMI patients, post-procedural OFDI identified flaps with minimal involvement of the intima in the proximal coronary arteries. A precise interpretation of FS may help decision making to avoid unnecessary procedures. (Clinical Trial Registration Information: ClinicalTrials.gov identifier: NCT01271361.).


Skeletal correlates for body mass estimation in modern and fossil flying birds.
Scaling relationships between skeletal dimensions and body mass in extant birds are often used to estimate body mass in fossil crown-group birds, as well as in stem-group avialans. However, useful statistical measurements for constraining the precision and accuracy of fossil mass estimates are rarely provided, which prevents the quantification of robust upper and lower bound body mass estimates for fossils. Here, we generate thirteen body mass correlations and associated measures of statistical robustness using a sample of 863 extant flying birds. By providing robust body mass regressions with upper- and lower-bound prediction intervals for individual skeletal elements, we address the longstanding problem of body mass estimation for highly fragmentary fossil birds. We demonstrate that the most precise proxy for estimating body mass in the overall dataset, measured both as coefficient determination of ordinary least squares regression and percent prediction error, is the maximum diameter of the coracoid's humeral articulation facet (the glenoid). We further demonstrate that this result is consistent among the majority of investigated avian orders (10 out of 18). As a result, we suggest that, in the majority of cases, this proxy may provide the most accurate estimates of body mass for volant fossil birds. Additionally, by presenting statistical measurements of body mass prediction error for thirteen different body mass regressions, this study provides a much-needed quantitative framework for the accurate estimation of body mass and associated ecological correlates in fossil birds. The application of these regressions will enhance the precision and robustness of many mass-based inferences in future paleornithological studies.


Midostaurin In Acute Myeloid Leukemia: An Evidence-Based Review And Patient Selection.
Fms-related-tyrosine kinase 3 (FLT3) mutations occur in approximately a third of acute myeloid leukemia (AML) patients and confer an adverse prognosis. Numerous studies have evaluated FLT3 targeting as single agent and in combination approaches in frontline and relapsed AML. At this time, midostaurin, a multikinase inhibitor, is the only FLT3-inhibitor that is US FDA approved to be used in combination with induction therapy in the frontline FLT3-mutated AML setting based on improved overall survival noted in the RATIFY Phase III trial. The utility of midostaurin in maintenance post stem cell transplantation has shown promising results and further studies are still ongoing. In this review, we discuss the studies that led to the inception of midostaurin as a targeted kinase inhibitor, its evaluation in AML, the early clinical trials and the large Phase III clinical trial that led to its eventual US FDA-approval in FLT3-mutated AML. Our review also discusses data on midostaurin adverse effects, mechanisms of resistance and limitations of its utility. We further discuss emerging second-generation FLT3 inhibitors, with a focus on quizartinib and gilteritinib and future directions to enhance FLT3-inhibitor efficacy and overcome mechanisms of resistance.


'Closer to my world': Children with autism spectrum disorder tell their stories through photovoice.
One of the challenges in doing research with individuals with autism spectrum disorder (ASD) is the difficulty in communication. This study employed a modified form of photovoice with a group of young people with ASD in Hanoi, Vietnam, to provide a means of meaningful participation in research about their lives, experiences, and needs. We describe the process of conducting photovoice with nine children with ASD from June 2011 to May 2012, many of whom had limited verbal communication skills. More than 2100 photos were taken by children. Undertaking photovoice with children with ASD required some modification of the method. In particular we consider the difficulties in analysing and interpreting the photographs produced by children with ASD. Due to the ambiguities of the visual images produced we found content analysis of photographs alone was inadequate. There was a discrepancy between our initial interpretations of the photographs and our understandings derived from information from interviews with children, parents, carers, and our own observations. Our study points to the need to understand context through multiple methods and the potential of photovoice as a means to mediate communication and participation in research for groups with communication difficulties.


Sequential [(18)F]FDG µPET whole-brain imaging of central vestibular compensation: a model of deafferentation-induced brain plasticity.
Unilateral inner ear damage is followed by a rapid behavioural recovery due to central vestibular compensation. In this study, we utilized serial [(18)F]Fluoro-deoxyglucose ([(18)F]FDG)-µPET imaging in the rat to visualize changes in brain glucose metabolism during behavioural recovery after surgical and chemical unilateral labyrinthectomy, to determine the extent and time-course of the involvement of different brain regions in vestibular compensation and test previously described hypotheses of underlying mechanisms. Systematic patterns of relative changes of glucose metabolism (rCGM) were observed during vestibular compensation. A significant asymmetry of rCGM appeared in the vestibular nuclei, vestibulocerebellum, thalamus, multisensory vestibular cortex, hippocampus and amygdala in the acute phase of vestibular imbalance (4 h). This was followed by early vestibular compensation over 1-2 days where rCGM re-balanced between the vestibular nuclei, thalami and temporoparietal cortices and bilateral rCGM increase appeared in the hippocampus and amygdala. Subsequently over 2-7 days, rCGM increased in the ipsilesional spinal trigeminal nucleus and later (7-9 days) rCGM increased in the vestibulocerebellum bilaterally and the hypothalamus and persisted in the hippocampus. These systematic dynamic rCGM patterns during vestibular compensation, were confirmed in a second rat model of chemical unilateral labyrinthectomy by serial [(18)F]FDG-µPET. These findings show that deafferentation-induced plasticity after unilateral labyrinthectomy involves early mechanisms of re-balancing predominantly in the brainstem vestibular nuclei but also in thalamo-cortical and limbic areas, and indicate the contribution of spinocerebellar sensory inputs and vestibulocerebellar adaptation at the later stages of behavioural recovery.


Preventing hypothermia in elective arthroscopic shoulder surgery patients: a protocol for a randomised controlled trial.
Patients having arthroscopic shoulder surgery frequently experience periods of inadvertent hypothermia. This common perioperative problem has been linked to adverse patient outcomes such as myocardial ischaemia, surgical site infection and coagulopathy. International perioperative guidelines recommend patient warming, using a forced air warming device, and the use of warmed intraoperative irrigation solutions for the prevention of hypothermia in at-risk patient groups. This trial will investigate the effect of these interventions on patients' temperature, thermal comfort, and total recovery time. The trial will employ a randomised 2 x 2 factorial design. Eligible patients will be stratified by anaesthetist and block randomised into one of four groups: Group one will receive preoperative warming with a forced air warming device; group two will receive warmed intraoperative irrigation solutions; group three will receive both preoperative warming and warmed intraoperative irrigation solutions; and group four will receive neither intervention. Participants in all four groups will receive active intraoperative warming with a forced air warming device. The primary outcome measures are postoperative temperature, thermal comfort, and total recovery time. Primary outcomes will undergo a two-way analysis of variance controlling for covariants such as operating room ambient temperature and volume of intraoperative irrigation solution. This trial is designed to confirm the effectiveness of these interventions at maintaining perioperative normothermia and to evaluate if this translates into improved patient outcomes. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY NUMBER: ACTRN12610000591055.


Spectral characterization and unmixing of intrinsic contrast in intact normal and diseased gastric tissues using hyperspectral two-photon microscopy.
Living tissues contain a range of intrinsic fluorophores and sources of second harmonic generation which provide contrast that can be exploited for fresh tissue imaging. Microscopic imaging of fresh tissue samples can circumvent the cost and time associated with conventional histology. Further, intrinsic contrast can provide rich information about a tissue's composition, structure and function, and opens the potential for in-vivo imaging without the need for contrast agents. In this study, we used hyperspectral two-photon microscopy to explore the characteristics of both normal and diseased gastrointestinal (GI) tissues, relying only on their endogenous fluorescence and second harmonic generation to provide contrast. We obtained hyperspectral data at subcellular resolution by acquiring images over a range of two-photon excitation wavelengths, and found excitation spectral signatures of specific tissue types based on our ability to clearly visualize morphology. We present the two-photon excitation spectral properties of four major tissue types that are present throughout the GI tract: epithelium, lamina propria, collagen, and lymphatic tissue. Using these four excitation signatures as basis spectra, linear unmixing strategies were applied to hyperspectral data sets of both normal and neoplastic tissue acquired in the colon and small intestine. Our results show that hyperspectral unmixing with excitation spectra allows segmentation, showing promise for blind identification of tissue types within a field of view, analogous to specific staining in conventional histology. The intrinsic spectral signatures of these tissue types provide information relating to their biochemical composition. These results suggest hyperspectral two-photon microscopy could provide an alternative to conventional histology either for in-situ imaging, or intraoperative 'instant histology' of fresh tissue biopsies.


Nanoliposomes and Nanoemulsions Based on Chia Seed Lipids: Preparation and Characterization.
Polyunsaturated fatty acids (PUFA) are important in reducing the risk for cardiovascular, metabolic and neurodegenerative diseases. Chia (Salvia hispanica L.) seeds contain high levels of omega-3 PUFA, α-linolenic acid (ALA) in particular, and are a potential source for development of omega-3 PUFA-based products. Our objective was to obtain and characterize chia seed lipids, focusing on phospholipid fraction, and to investigate their use in the formulation of nanoemulsions (NE) and nanoliposomes (NL). Solvent-based lipid extraction was performed on the ORURO variety of chia seeds, followed by lipid composition analysis using GC and LC-MS and physico-chemical characterization of chia NL and NE. Folch extraction led to a slightly higher yield of ALA as compared to Soxhlet extraction. Lipid, phospholipid, and fatty acid composition analysis of the oil and residue revealed that the residue was rich in phospholipids; these were used to prepare NE and NL. Physico-chemical characterization showed that NE and NL were generally spherical (transmission electron microscopy), with a size of <120 nm under hydrated conditions that remained stable over 5 days. In conclusion, chia oil and phospholipid-rich residue can be used to obtain stable NL or NE using a simple method that involves spontaneous emulsification during lipid hydration, which potentially may be useful in cosmetics, pharmaceutical, and other health applications.


Coronary-artery bypass surgery in patients with left ventricular dysfunction.
The role of coronary-artery bypass grafting (CABG) in the treatment of patients with coronary artery disease and heart failure has not been clearly established. Between July 2002 and May 2007, a total of 1212 patients with an ejection fraction of 35% or less and coronary artery disease amenable to CABG were randomly assigned to medical therapy alone (602 patients) or medical therapy plus CABG (610 patients). The primary outcome was the rate of death from any cause. Major secondary outcomes included the rates of death from cardiovascular causes and of death from any cause or hospitalization for cardiovascular causes. The primary outcome occurred in 244 patients (41%) in the medical-therapy group and 218 (36%) in the CABG group (hazard ratio with CABG, 0.86; 95% confidence interval [CI], 0.72 to 1.04; P=0.12). A total of 201 patients (33%) in the medical-therapy group and 168 (28%) in the CABG group died from an adjudicated cardiovascular cause (hazard ratio with CABG, 0.81; 95% CI, 0.66 to 1.00; P=0.05). Death from any cause or hospitalization for cardiovascular causes occurred in 411 patients (68%) in the medical-therapy group and 351 (58%) in the CABG group (hazard ratio with CABG, 0.74; 95% CI, 0.64 to 0.85; P<0.001). By the end of the follow-up period (median, 56 months), 100 patients in the medical-therapy group (17%) underwent CABG, and 555 patients in the CABG group (91%) underwent CABG. In this randomized trial, there was no significant difference between medical therapy alone and medical therapy plus CABG with respect to the primary end point of death from any cause. Patients assigned to CABG, as compared with those assigned to medical therapy alone, had lower rates of death from cardiovascular causes and of death from any cause or hospitalization for cardiovascular causes. (Funded by the National Heart, Lung, and Blood Institute and Abbott Laboratories; STICH ClinicalTrials.gov number, NCT00023595.).


Neuropsychologic impairment in astrocytoma survivors.
Thirteen patients selected for long-term survival with primary astrocytic tumor (who failed to return to premorbid educational or vocational levels) were examined by neuropsychologic tests of specific and generalized higher cortical functions. In the absence of tumor regrowth or other neurologic disorders, each demonstrated difficulty in problem solving or coping with novel situations when previously acquired abilities, overlearned material, and psychometric intelligence appeared consistent with their premorbid level. The diffuse difficulties were unrelated to tumor type or location, and were not explicable by existing focal deficits, psychotic or depressive thought disorders, metabolic difficulties, or hydrocephalus. These examinations explained in part why these patients failed to resume active social lives or premorbid employment. The diffuse cortical dysfunction was most notable on the Category Test, Trails B, and Localization component of the Tactual Performance Test.


Therapeutic integration of c-myc and bcl-2 antisense molecules with docetaxel in a preclinical model of hormone-refractory prostate cancer.
The response of hormone-refractory prostate cancer (HRPC) to chemotherapy remains modest, necessitating the search for new forms of treatment to improve the prognosis. Since an increased expression of oncogenes, including c-myc and bcl-2, accompanies the transition to HRPC, we evaluated whether the concomitant downregulation of these oncogenes by antisense strategy sensitized HRPC to chemotherapy. PC-3 prostate cancer cells were exposed in vitro to c-myc (INX-6295) and bcl-2 (G3139) antisense oligodeoxynucleotides (ODNs) and docetaxel given alone or in combination. Therapeutic efficacy of the different treatments was also evaluated in xenografts. We show that the triple combination of drugs given in the sequence G3139/docetaxel/INX-6295 was the most active in reducing the survival of PC-3. Likewise, the combination triggered apoptosis in more than 80% of cells. A marked tumor weight inhibition was observed in PC-3 xenografts after G3139/docetaxel/INX-6295 treatment, with a complete tumor regression being noted in half the mice. A 111% overall increase in life survival and a complete cure in two out of eight mice was also reported. This treatment remained effective even when started at a very late stage of tumor growth producing about 80% tumor weight inhibition (TWI), with tumor regression being maintained for 1 month. Finally, the antitumor effect resulted in a significant increase (70%) in mice survival. These data indicate that the combined targeting of genes involved in uncontrolled proliferation and evasion of apoptosis renders HRPC responsive to chemotherapy making this treatment a promising antineoplastic strategy.


Symmetry correlations between crystallographic and photoluminescence study of ternary β-diketone europium(iii) based complexes using 1,10-phenanthroline as the ancillary ligand.
This work entails deep red emitting EuIII based complexes with a variety of ternary β-diketonate ligands and 1,10-phenanthroline as the ancillary ligand in the system. The solid state structure and spectroscopic analysis has been outlaid in terms of photoluminescence and crystallography. A luminescence quantum efficiency of 50% was obtained for the [tris-(4,4,4-trifluoro-1-chlorophenyl-butanedione)mono-(1,10-phenanthroline)europium(iii)] complexes. Moreover, complexes [tris-(2,2,6,6-tetramethyl-heptanedione)mono-(1,10-phenanthroline) europium(iii)] and {[hexa-(benzyl carboxylic acid) bis-(1,10-phenanthroline)di-europium(iii)]-μ-[κ2-O,O'-(benzyl carboxylic acid)]2} were found to also have quantum yields of 9% and 28% with respective sensitization efficiencies of 85%, 15% and 58%. These results were articulated with crystallographic details pertaining to the nature of coordination and the effect of steric and electronic properties thereof which somewhat impacts the Eu-N bond distances. A symmetry correlation was drawn between the crystallographic data and the photoluminescence data.