Orthopedic disease burden in adult patients with symptomatic lumbar scoliosis: results from a prospective multicenter study.
Although the health impact of adult symptomatic lumbar scoliosis (ASLS) is substantial, these patients often have other orthopedic problems that have not been previously quantified. The objective of this study was to assess disease burden of other orthopedic conditions in patients with ASLS based on a retrospective review of a prospective multicenter cohort. The ASLS-1 study is an NIH-sponsored prospective multicenter study designed to assess operative versus nonoperative treatment for ASLS. Patients were 40-80 years old with ASLS, defined as a lumbar coronal Cobb angle ≥ 30° and Oswestry Disability Index ≥ 20, or Scoliosis Research Society-22 questionnaire score ≤ 4.0 in pain, function, and/or self-image domains. Nonthoracolumbar orthopedic events, defined as fractures and other orthopedic conditions receiving surgical treatment, were assessed from enrollment to the 4-year follow-up. Two hundred eighty-six patients (mean age 60.3 years, 90% women) were enrolled, with 173 operative and 113 nonoperative patients, and 81% with 4-year follow-up data. At a mean (± SD) follow-up of 3.8 ± 0.9 years, 104 nonthoracolumbar orthopedic events were reported, affecting 69 patients (24.1%). The most common events were arthroplasty (n = 38), fracture (n = 25), joint ligament/cartilage repair (n = 13), and cervical decompression/fusion (n = 7). Based on the final adjusted model, patients with a nonthoracolumbar orthopedic event were older (HR 1.44 per decade, 95% CI 1.07-1.94), more likely to have a history of tobacco use (HR 1.63, 95% CI 1.00-2.66), and had worse baseline leg pain scores (HR 1.10, 95% CI 1.01-1.19). Patients with ASLS have high orthopedic disease burden, with almost 25% having a fracture or nonthoracolumbar orthopedic condition requiring surgical treatment during the mean 3.8 years following enrollment. Comparisons with previous studies suggest that the rate of total knee arthroplasty was considerably greater and the rates of total hip arthroplasty were at least as high in the ASLS-1 cohort compared with the similarly aged general US population. These conditions may further impact health-related quality of life and outcomes assessments of both nonoperative and operative treatment approaches in patients with ASLS.


Bronchoscopic photography of a bronchial carcinoid tumor associated with unilateral hypoperfusion of the lung.
A patient with a bronchial carcinoid-producing unilateral hypoperfusion of the lung is described. Bronchoscopic photographs show the adenoma to assume different intrabronchial positions during inspiration and expiration. Although patent during inspiration, the lumen was effectively occluded during expiration. The adenoma exhibited a ball-valve movement which is speculated to be the initial mechanism of hypoperfusion in this setting.


Comparative Evaluation of Occlusal Bite Force in Relation to the Muscle Activity in the Mixed Dentition Children of Age Group 9-12 Years: A T-scan Analysis.
Compare and evaluate the muscle activity and the occlusal force between the mixed dentition boys and girls of 9-12 years. The study included 15 boys and 15 girls. The occlusal force and activity of the masseter and temporalis muscle were measured with a T-scan device using a sensor, a module to transmit the signals to a computer and the complete data of the bite force and muscle activity with the EMG recordings and data were collected and evaluated. Relative occlusal force in the primary and permanent molars between the boys and girls showed no significant difference on the left side compared to the right. The electromyography values of masseter and temporalis in boys and girls showed a significant difference in which (TAR and MMR), (TAR and MML), (TAL and MMR), and (TAL and MML) are significant. The overall paired sample statistics showed higher muscle activity in masseter. T-scan analysis has proved to be a dependable method for the evaluation of occlusal bite force with the muscle activity interpretation using EMG. This study concluded that there is a difference in the occlusal pattern and muscle activity in the mixed dentition that showed the maximum force was on the permanent molars and the symmetry of EMGs activity in children was on the right masseter comparatively with higher bite values in boys compared to girls. T-scan is a computerized analysis system that helps in the proper assessment of the patient's occlusion and assists in the proper treatment planning and diagnosis accurately without much effort. Prabahar T, Gupta N, Chowdhary NR, et al. Comparative Evaluation of Occlusal Bite Force in Relation to the Muscle Activity in the Mixed Dentition Children of Age Group 9-12 Years: A T-scan Analysis. Int J Clin Pediatr Dent 2021;14(S-1):S29-S34.


Cross-modal pattern of brain activations associated with the processing of self- and significant other's name.
Previous neuroimaging studies have shown that the patterns of brain activity during the processing of personally relevant names (e.g., own name, friend's name, partner's name, etc.) and the names of famous people (e.g., celebrities) are different. However, it is not known how the activity in this network is influenced by the modality of the presented stimuli. In this fMRI study, we investigated the pattern of brain activations during the recognition of aurally and visually presented full names of the subject, a significant other, a famous person and unknown individuals. In both modalities, we found that the processing of self-name and the significant other's name was associated with increased activation in the medial prefrontal cortex (MPFC). Acoustic presentations of these names also activated bilateral inferior frontal gyri (IFG). This pattern of results supports the role of MPFC in the processing of personally relevant information, irrespective of their modality.


Elucidation of the structural role of fluorine in potentially bioactive glasses by experimental and computational investigation.
Glasses belonging to the Na(2)O-CaO-P(2)O(5)-SiO(2) system and modified by CaF(2) substitution for CaO and Na(2)O alternatively, were synthesized and characterized experimentally and computationally. The results of molecular dynamics simulations show that fluorine is almost exclusively bonded to modifier cations (Ca and Na) with coordination number close to 4. A similar mean coordination number value is found in the crystal phases obtained by means of thermal treatment at fixed temperature. Addition of fluorine increases the polymerization of silicate tetrahedra by removing modifiers from the siliceous matrix. No appreciable amount of Si-F bonds are detected.


Investigating microbial (micro)colony heterogeneity by vibrational spectroscopy.
Fourier transform infrared and Raman microspectroscopy are currently being developed as new methods for the rapid identification of clinically relevant microorganisms. These methods involve measuring spectra from microcolonies which have been cultured for as little as 6 h, followed by the nonsubjective identification of microorganisms through the use of multivariate statistical analyses. To examine the biological heterogeneity of microorganism growth which is reflected in the spectra, measurements were acquired from various positions within (micro)colonies cultured for 6, 12, and 24 h. The studies reveal that there is little spectral variance in 6-h microcolonies. In contrast, the 12- and 24-h cultures exhibited a significant amount of heterogeneity. Hierarchical cluster analysis of the spectra from the various positions and depths reveals the presence of different layers in the colonies. Further analysis indicates that spectra acquired from the surface of the colonies exhibit higher levels of glycogen than do the deeper layers of the colony. Additionally, the spectra from the deeper layers present with higher RNA levels than the surface layers. Therefore, the 6-h colonies with their limited heterogeneity are more suitable for inclusion in a spectral database to be used for classification purposes. These results also demonstrate that vibrational spectroscopic techniques can be useful tools for studying the nature of colony development and biofilm formation.


Simultaneous Determination of Posaconazole and Hemp Seed Oil in Nanomicelles through RP-HPLC via a Quality-by-Design Approach.
The present study involves the development of a reverse-phase HPLC method employing the quality-by-design methodology for the estimation of posaconazole and hemp seed oil simultaneously in nanomicelles formulation. The successful separation of posaconazole and hemp seed oil was achieved together, and this is the first study to develop and quantify posaconazole and hemp seed oil nanomicelles with linoleic acid as the internal standard and developed a dual drug analytical method employing a quality-by-design approach. The study was performed on a Shimadzu Prominence-I LC-2030C 3D Plus HPLC system with a PDA detector and the Shim-pack Solar C8 column (250 mm × 4.6 mm × 5 μm) for analysis with a mobile phase ratio of methanol:water (80:20% v/v) maintaining the flow rate of 1.0 mL/min. The final wavelength was selected as 240 nm and the elution of hemp seed oil and posaconazole was obtained at 2.7 and 4.6 min, respectively, with a maximum run time of 8.0 min. Box Behnken design was employed to optimize the method, keeping the retention time, peak area, and theoretical plates as dependent variables, while the mobile phase composition, flow rate, and wavelengths were chosen as independent variables. Parameters such as specificity, accuracy, robustness, linearity, sensitivity, precision, ruggedness, and forced degradation study were performed to validate the method. The calibration curves of posaconazole and hemp seed oil were determined to be linear throughout the range for concentration. The suggested approach can be effectively utilized for estimating the content of drugs from their nanoformulation and proved suitable for both in vivo and in vitro research.


Five myths about cancer care in America.
In this commentary we debunk a number of the most common misconceptions about cancer treatment, such as claims that the war on cancer has been a failure and that treatment costs are unsustainable. In addition, there is good evidence that patients value these treatments more highly than traditional cost-effectiveness analysis would indicate. We argue that coverage policies placing undue burden on patients are socially wasteful and will likely discourage further innovation.


Mitoxantrone: a review of its use in multiple sclerosis.
Mitoxantrone (Novantrone), a synthetic anthracenedione derivative, is an antineoplastic, immunomodulatory agent. Its presumed mechanism of action in patients with multiple sclerosis (MS) is via immunomodulatory mechanisms, although these remain to be fully elucidated. Intravenous mitoxantrone treatment improved neurological disability and delayed progression of MS in patients with worsening relapsing-remitting (RR) [also termed progressive-relapsing (PR) MS] or secondary-progressive (SP) disease. In a pivotal randomised, double-blind, multicentre trial, mitoxantrone 12 mg/m(2) administered once every 3 months for 2 years provided significant improvements in neurological disability ratings, including Kurtzke Expanded Disability Status Scale (EDSS), Ambulatory Index (AI) and Standardised Neurological Status (SNS) scores, compared with placebo. The drug also significantly reduced the mean number of corticosteroid-treated relapses and prolonged the time to the first treated relapse, with the beneficial effects on disease progression supported by magnetic resonance imaging. Post hoc analyses suggest that the benefits associated with mitoxantrone treatment may be sustained for at least 12 months after cessation of treatment, mean changes from baseline at 36 months in EDSS, AI and SNS scores of 0.10, 0.61 and 0.19, respectively, in the mitoxantrone group versus 0.46, 1.13 and 3.38 with placebo. Concomitant intravenous mitoxantrone 20mg plus intravenous methylprednisolone 1g once every month for 6 months was more effective than intravenous methylprednisolone monotherapy in preventing the development of new gadolinium-enhanced lesions in patients with very active RRMS or SPMS. The drug was generally well tolerated in patients with MS. Adverse events were generally mild to moderate in severity and usually resolved upon discontinuation of treatment or with appropriate pharmacotherapy. At the recommended dosage, mitoxantrone appears to have a low potential to cause cardiotoxicity. In conclusion, intravenous mitoxantrone reduces the relapse rate and slows progression of the disease in patients with worsening RRMS, PRMS or SPMS; thus providing a new option for the management of these patients. The drug was generally well tolerated at the recommended dosage, although potential cardiotoxicity limits the total cumulative dose to 140 mg/m(2). Further studies are warranted to determine which patients with worsening RRMS, PRMS or SPMS are most likely to benefit from mitoxantrone treatment and to more fully define the long-term safety and tolerability of mitoxantrone, including the use of concomitant cardioprotectants to extend the therapeutic lifespan of the drug. Pharmacodynamic Profile. Mitoxantrone, a synthetic anthracenedione derivative, is an established cytotoxic, antineoplastic agent. Its presumed mechanism of action in multiple sclerosis (MS) is immunosuppression. In antineoplastic studies, the drug showed several immunomodulatory effects, inducing macrophage-mediated suppression of B-cell, T-helper and T-cytotoxic lymphocyte function. Currently, the pharmacodynamic properties of mitoxantrone have not been investigated to any extent in patients with MS. In one study, 6 months' treatment with intravenous mitoxantrone generally had no effect on the distribution of cytokine-positive peripheral blood monocyte cells in patients with MS. In an animal model of the disease, mitoxantrone suppressed the development and progression of both actively and passively induced acute experimental allergic encephalomyelitis (EAE). It appeared to be 10-20 times more effective than cyclophosphamide in the suppression of EAE. Moreover, mitoxantrone approximately doubled the mean time to onset of EAE versus control animals (279 vs 148 days after immunisation; p < 0.00005). In vitro, mitoxantrone 10 and 100 micro g/L inhibited myelin degradation by leucocytes and peritoneal macrophages derived from mice with acute EAE by approximately 60% and 100%. Pharmacokinetic Profile. Currently, there are no published pharmacokinetic data for intravenous mitoxantrone in pitoxantrone in patients with MS, paediatric patients or in those with renal impairment. All studies, to date, have been in patients with cancer receiving a single, approximately 30-minute intravenous infusion of mitoxantrone 5-14 mg/m(2). The drug exhibits triexponential pharmacokinetics, with a rapid initial distribution (alpha) phase, an intermediate distribution (beta) phase and a much slower elimination (gamma) phase. The mean half-life of the alpha phase appears to be 6-12 minutes and that of the beta phase 1.1-3.1 hours. Mitoxantrone has a high affinity for tissue, with a volume of distribution of up to 2248 L/m(2). Mitoxantrone persists for prolonged periods in tissues and was detectable in autopsy tissue from patients who last received the drug up to 272 days before death. At concentrations of 10-10000 ng/mL, the drug was 70-80 % bound to plasma proteins in dogs. Elimination of mitoxantrone occurs predominantly through biliary excretion and may be impaired in patients with hepatic dysfunction or third space abnormalities (e.g. ascites). The mean terminal elimination half-life of mitoxantrone ranged from 23 hours to 215 hours. Renal clearance accounts for 10 % of the total clearance of the drug. Total clearance of mitoxantrone ranged from 13 to 34.2 L/h/m(2) and renal clearance from 0.9 to 2.7 L/h/m(2). The drug appears to have a low potential for interaction with other concomitantly administered agents. Therapeutic Efficacy. Intravenous mitoxantrone (infusion of > or = 5 minutes), either as monotherapy or in combination with intravenous methylprednisolone, delayed the progression of the disease in patients with secondary-progressive (SP) or worsening relapsing-remitting (RR) MS (the latter is also termed progressive-relapsing MS) in comparative, randomised, multicentre trials. In a double-blind, monotherapy trial (Mitoxantrone In Multiple Sclerosis [MIMS] trial), mitoxantrone 12 mg/m(2) (n = 60) once every 3 months for 2 years significantly improved neurological disability relative to placebo (n = 64), as assessed by changes in mean Kurtzke Expanded Disability Status Scale (EDSS) score, mean Ambulatory Index (AI) score and mean Standardised Neurological Status (SNS) score. The drug also significantly reduced the mean number of corticosteroid-treated relapses per patient and prolonged the time to the first treated relapse. A Wei-Lachin multivariate analysis of these five efficacy variables indicated that the global difference between the two treatment groups was 0.30 (p < 0.0001). Mitroxantrone was also more effective than placebo according to secondary endpoints in this study, with fewer mitoxantrone recipients experiencing a relapse, a deterioration of > or =1 EDSS point or a confirmed deterioration in EDSS score over a 3-month period. Mitoxantrone recipients also showed less deterioration in quality-of-life ratings and had fewer hospital admissions, whereas more placebo recipients had new gadolinium-enhanced lesions at study end (the latter parameter was assessed using magnetic resonance imaging [MRI] in a subgroup of 110 patients, including 40 patients who received an exploratory 5 mg/m(2) dose). Furthermore, post hoc analyses indicated that the beneficial effects of mitoxantrone treatment on EDSS, SNS and AI scores were sustained for at least 12 months after cessation of treatment, with mean changes from baseline at 36 months in EDSS, AI and SNS scores of 0.10, 0.61 and 0.19, respectively, in the mitoxantrone group versus 0.46, 1.13 and 3.38 with placebo. Preliminary data from a cost-minimisation analysis based on results from the MIMS trial indicated that approximately half of the cost of mitoxantrone was offset by cost savings in other areas associated with the treatment of MS (direct and indirect major costs), with a total annual incremental cost for mitoxantrone of dollar 1661 per patient. Combination therapy once-monthly with intravenous mitoxantrone 20mg plus intravenous methylprednisolone 1g was more effective than intravenous methylprednisolone 1g once every month in preventing the development of gadolinium-enhanced lesions in patients with very active RRMS or SPMS (double-blind assessment using MRI scans). After 6 months, significantly more combination therapy recipients had no new gadolinium-enhanced lesions (90.5% vs 31.3% with monotherapy; p < 0.001) [primary endpoint]. There were also significant reductions in both the mean number of new enhancing lesions and the total number of gadolinium-enhanced lesions in patients receiving combination therapy versus methylprednisolone monotherapy.Tolerability. Mitoxantrone was generally well tolerated in patients with MS. Treatment-emergent adverse events occurring significantly more frequently with mitoxantrone (12 mg/m(2) once every 3 months for 2 years) than placebo were nausea, alopecia, menstrual disorders, urinary tract infection, amenorrhoea, leucopenia and elevated gamma-glutamyltranspeptidase levels. Adverse events were usually mild to moderate in severity and generally resolved with discontinuation of treatment or when treated with appropriate pharmacotherapy. Eight percent of patients discontinued treatment in the mitoxantrone 12 mg/m(2) group due to an adverse event versus 3% of placebo recipients. The incidence of drug-related acute myelogenous leukaemia was very low (0.12%) in a cohort of 802 patients with MS receiving mitoxantrone. Evidence suggests that the risk of cardiotoxicity is low in patients with MS. After 1 year of monotherapy, 3.4% of mitoxantrone recipients had a reduction in left ventricular ejection fraction (LVEF) to < or =50% compared with 0% of placebo recipients; at the end of the second year, respective incidences were 1.9% and 2.9% (total cumulative dose of mitoxantrone per patient was 96 mg/m(2) after 2 years' treatment). (ABSTRACT TRUNCATED)


Substantial differences in the diagnostic criteria used by diabetes experts.
A survey of twenty diabetologists revealed that they employ diagnostic criteria differing quite substantially. In some populations, including the general population of the United States, these disparities would result in very major differences in the rates of "diabetes." Under certain common circumstances, some diabetologists would classify as normal more than half of the one- and two-hour values considered to be abnormal by other well-qualified diabetologists.


[A 13-week oral toxicity study of prulifloxacin (NM441) in dogs followed by a 5-week recovery test].
A repeated dose toxicity study of prulifloxacin, a new antibacterial agent, was conducted in beagle dogs. Male and female dogs were given the test material orally for 13 weeks at doses of 0 (control), 20, 100 and 500 mg/kg. After discontinuation of the treatment, a 5-week recovery test was also conducted. Vomiting, salivation and decreased body weight gain or reduced body weight were seen in the 100 and 500 mg/kg groups. In the 500 mg/kg group, tremor, paresis of posterior limb associated with prone or sitting position and decreased food consumption were also observed. There were no treatment-related effects on survival and water consumption. Ophthalmoscopic, electrocardiographic and hematologic examinations, and urinalysis failed to show any abnormalities attributable to the treatment. Blood chemical examination showed increased GPT and decreased beta- and gamma-globulins in the 100 and 500 mg/kg groups, and increased GOT in the 500 mg/kg group. In pathological examination, cavitations and erosions were seen in the humeral and femoral articular cartilages in the 100 and 500 mg/kg groups. The above-mentioned changes were satisfactorily reversible except for erosions in the humeral and femoral articular cartilages in the 100 and 500 mg/kg groups. No toxicological findings were seen in the 20 mg/kg group. The results show that the NOAEL of prulifloxacin is 20 mg/kg for 13-week repeated dose toxicity in dogs.


Adhesive and non-adhesive membrane domains of amphibian embryo cells.
Superficial blastomeres of mid-cleavage stage amphibian embryos (32- and 64-cell stage) display regional cell-surface differences in adhesiveness. The cells are adhesive on the lateral and basal cell surfaces and non-adhesive on the apical surface. These adhesive differences are maintained by single cells which have been dissociated from the intact embryo. Pigmentation differences afford a means of distinguishing apical surface from basal/lateral surface in dissociated cells. The apical surface is underlain by melanin granules and so appears dark, whereas the lateral and basal surfaces lack pigment and are white. Scanning electron-micrograph observations of isolated superficial cells reveal striking morphological differences between the adhesive and non-adhesive regions. The apical (non-adhesive) portion of the cell surface has a convoluted appearance and is almost entirely devoid of microvilli. The lateral and basal (adhesive) surfaces lack the convolutions of the apical surface and bear scattered microvilli. The isolated superficial cells continue to divide in culture. The cells display a unilateral or one-sided furrow which begins in the basal surface and progresses toward the apical surface. The plane of cleavage of most of the cells is oriented such that the pigmented cap is bisected, with very few cells having the plane of the furrow pass parallel to the apical surface. The direction of furrowing in the isolated cells from the 32- to 64-cell embryo represents a direction of furrow progression in the intact embryo from the interior to the surface. Since the early cleavages are initiated at the surface and progress into the interior, it is suggested that a reversal in direction of furrowing occurs by mid-cleavage stages.


Brown adipose tissue: what have we learned since its recent identification in human adults.
Brown adipose tissue, an essential organ for thermoregulation in small and hibernating mammals due to its mitochondrial uncoupling capacity, was until recently considered to be present in humans only in newborns. The identification of brown adipose tissue in adult humans since the development and use of positron emission tomography marked with 18-fluorodeoxyglucose (PET-FDG) has raised a series of doubts and questions about its real importance in our metabolism. In this review, we will discuss what we have learnt since its identification in humans as well as both new and old concepts, some of which have been marginalized for decades, such as diet-induced thermogenesis.


[Frailty, an enigmatic and controversial concept in geriatrics. The biological perspective].
Frailty is a controversial, complex and enigmatic concept. Because the world's population is aging, it has been possible to assess the impact of frailty over patients themselves as well as on their relatives, community and mainly on their caregivers. Health care personnel must be able to identify and understand this entity and its components. In addition during the 80's frailty was understood as synonymous with disability, chronic illness, or extreme aging; this perspective must be modified. The literature on frailty has increased exponentially in the last years. However, there is still not a well defined and universally recognized description or definition. The purpose of this review was to understand frailty and its consequences based on the most recent advances in the field of aging. Frialty is a multifactorial phenomenon and for purposes of this review, only biological characteristics are discussed.


Catch me if you can: how the histone chaperone FACT capitalizes on nucleosome breathing.
Nucleosomes confer a barrier to processes that require access to the eukaryotic genome such as transcription, DNA replication and repair. A variety of ATP-dependent nucleosome remodeling machines and ATP-independent histone chaperones facilitate nucleosome dynamics by depositing or evicting histones and unwrapping the DNA. It is clear that remodeling machines can use the energy from ATP to actively destabilize, translocate or disassemble nucleosomes. But how do ATP-independent histone chaperones, which "merely" bind histones, contribute to this process? Using our recent structural analysis of the conserved and essential eukaryotic histone chaperone FACT in complex with histones H2A-H2B as an example, we suggest that FACT capitalizes on transiently exposed surfaces of the nucleosome. By binding these surfaces, FACT stabilizes thermodynamically unfavorable intermediates of the intrinsically dynamic nucleosome particle. This makes the nucleosome permissive to DNA and RNA polymerases, providing temporary access, passage, and read-out.


Mycobacteriosis in wild rabbitfish Siganus rivulatus associated with cage farming in the Gulf of Eilat, Red Sea.
Infection patterns of Mycobacterium marinum were studied over a period of 3 yr in wild rabbitfish Siganus nivulatus populations associated with commercial mariculture cages and inhabiting various sites along the Israeli Red Sea coastline. Mycobacteriosis was first recorded from the Red Sea in 1990 in farmed sea bass Dicentrarchus labrax and is absent from records of studies on parasites and diseases of wild rabbitfish carried out in the 1970s and 1980s. A sharp increase in the prevalence of the disease in cultured and wild fish in the region has occurred since. A total of 1142 rabbitfish were examined over a 3 yr period from inside mariculture net cages, from the cage surroundings and from several sites along the coast. Histological sections of spleens were examined for presence of granulomatous lesions. Overall prevalence levels of 50% were recorded in the rabbitfish sampled inside the net cages and 39% at the cages' close surroundings, 21% at a sandy beach site 1.2 km westwards, 35% at Eilat harbour 3 km to the south and 42% at a coral reef site about 10 km south of the cages. In addition, 147 fish belonging to 18 native Red Sea species were sampled from 2 sites, the net cage farm perimeter and the coral reef area, and examined for similar lesions. None of those from the coral reef were infected with Mycobacterium; however, 9 of 14 species collected from the cage surroundings were infected. An increase in prevalence of mycobacteriosis in the mariculture farm area was noted from 1995 to 1997. At the same time, a significant increase in prevalence was also apparent at the coral reef sampling site. Two M. marinum isolates from rabbitfish captured at Eilat harbour and the coral reef site were shown by 16S rDNA sequencing analysis to be identical to isolates from rabbitfish trapped inside the mariculture cages as well as isolates from locally cultured sea bass D. labrax. The implications of spreading of M. marinum infection in wild fish populations in the Gulf of Eilat are discussed.


The role of beta-carotene and other dietary factors in the aetiology of cervical dysplasia: results of a case-control study.
The effects of beta-carotene and several other dietary factors on the risk of cervical dysplasia were evaluated in a case-control study. Cases (n = 257) were the participants of a randomized trial assessing the effect of beta-carotene on cervical dysplasia. Controls (n = 705) were sampled from the general population. A postal questionnaire was used to obtain information about the frequency of consumption of several food items containing beta-carotene, retinol, vitamin C and dietary fibre. Information was also collected about other risk factors for cervical dysplasia, in order to adjust for possible confounding. To our surprise, we observed an increased risk of cervical dysplasia for women with a high intake of beta-carotene (odds ratio (OR) = 2.31; 95% confidence interval (CI): 1.27-4.19). No relationship was found with the intake of retinol, while both vitamin C and dietary fibre showed a weak and not statistically significant inverse relationship with cervical dysplasia. These findings do not support the hypothesis that beta-carotene protects against cervical dysplasia.


Vascular cognitive impairment: Modeling a critical neurologic disease in vitro and in vivo.
Vascular contributions to cognitive impairment and dementia (VCID) is a complex form of dementia, combining aspects of vascular disease and other forms of dementia, such as Alzheimer's disease. VCID encompasses a wide spectrum of cerebrovascular-driven cognitive impairment, from mild cognitive impairment to fully developed dementia. This disease state is further complicated by metabolic disorders, such as type 2 diabetes and hypertension, and lifestyle factors, like obesity and high fat diets. This manuscript is meant to both define VCID and review the in vitro and in vivo models of the disease state. This includes in vitro models of the neurovascular unit, models of chronic cerebral hypoperfusion, animals with NOTCH3 mutations as a model of small vessel disease, large animals with cerebral amyloid angiopathy (CAA), and animal models of mixed dementia. Synthetic microvessels are a promising technique to study the neurovascular unit and canines, despite the cost, are an excellent model to study CAA. While there are several good models of individual aspects of VCID, the heterogeneity of the disease states prevents them from being a model of all aspects of the disease. Therefore, VCID needs to be further defined into disease states that exist within this umbrella term. This includes specific guidelines for stroke counts and stroke locations and further categorization of overlapping cerebrovascular and AD pathologies that contribute to dementia. This will allow for better models and a more thorough understanding of how vascular disease contributes to dementia. VCID is the second most common form of dementia and is expected to increase in coming years. The heterogeneity of VCID makes it difficult to study, but without better definitions and models, VCID presents a major public health problem for our aging population. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.


Free electron laser lithotripsy: threshold radiant exposures.
To determine the threshold radiant exposures (J/cm2) needed for ablation or fragmentation as a function of infrared wavelengths on various urinary calculi and to determine if there is a relation between these thresholds and lithotripsy efficiencies with respect to optical absorption coefficients. Human calculi composed of uric acid, calcium oxalate monohydrate (COM), cystine, or magnesium ammonium phosphate hexahydrate (MAPH) were used. The calculi were irradiated in air with the free electron laser (FEL) at six wavelengths: 2.12, 2.5, 2.94, 3.13, 5, and 6.45 microm. Threshold radiant exposures increased as optical absorption decreased. At the near-infrared wave-lengths with low optical absorption, the thresholds were >1.5 J/cm2. The thresholds decreased below 0.5 J/cm2 for regions of high absorption for all the calculus types. Thresholds within the high-absorption regions were statistically different from those in the low-absorption regions, with P values much less than 0.05. Optical absorption coefficients or threshold radiant exposures can be used to predict lithotripsy efficiencies. For low ablation thresholds, smaller radiant exposures were required to achieve breakdown temperatures or to exceed the dynamic tensile strength of the material. Therefore, more energy is available for fragmentation, resulting in higher lithotripsy efficiencies.


[Treatment of osteoporotic vertebral compression. Explosive interest for vertebroplasty and kyphoplasty].
During the last 15 years, two new treatment strategies have gained worldwide attention in the treatment of osteoporotic vertebral fractures. The exponential increase in the use of percutaneous vertebro- or kyphoplasty has up to now not been supported by scientific sound evidence-based data. There exist no prospective randomised controlled trials (RCT) that support the efficacy of the treatments, not even adequate controlled studies. Instead we have to rely on prospective and retrospective uncontrolled short-term observational studies and case-control studies. These studies consistently indicate that the short-term results after the procedures in the treatment of osteoporotic vertebral fractures are favourable, regarding both pain relief and functional status. However, if a vertebro- or a kyphoplasty produces a better outcome than conservative treatment, and if the long-term results are as favourable as the short-term results in the treatment of osteoporotic vertebral fractures, is currently unknown.


Photosensitizer-incorporated quadruplex DNA-gated nanovechicles for light-triggered, targeted dual drug delivery to cancer cells.
A novel light-operated vehicle for targeted intracellular drug delivery is constructed using photosensitizer-incorporated G-quadruplex DNA-capped mesoporous silica nanoparticles. Upon light irradiation, the photosensitizer generates ROS, causing the DNA capping to be cleaved and allowing cargo to be released. Importantly, this platform makes it possible to develop a drug-carrier system for the synergistic combination of chemotherapy and PDT for cancer treatment with spatial/temporal control. Furthermore, the introducing of targeting ligands further improves tumor targeting efficiency. The excellent biocompatibility, cell-specific intracellular drug delivery, and cellular uptake properties set up the basis for future biomedical application that require in vivo controlled, targeted drug delivery.


The Functional Assessment of Cancer Therapy - General (FACT-G) is valid for monitoring quality of life in patients with non-Hodgkin lymphoma.
Quality of life (QoL) is an important outcome in patients with non-Hodgkin lymphoma (NHL). We assessed the validity of administering the Functional Assessment of Cancer Therapy - General (FACT-G) at 12-month intervals over 3 years in a longitudinal study of 611 prospectively enrolled, newly diagnosed patients with NHL. We evaluated corrected item-total correlation and percent missing to identify items that may be less useful in certain NHL patient subgroups. The FACT-G subscales and total score demonstrated good internal consistency reliability, convergent validity and known-groups validity. Most scores also demonstrated good responsiveness to change. Questions that could be problematic included GE3 (losing hope) and GP2 (nausea) for patients in remission, and GP5 (bothered by side effects) for patients being observed. Overall, the FACT-G was a valid measure for monitoring QoL over time in patients with NHL. However, sensitivity analyses based on subscale scoring that excludes potentially problematic items may be warranted.


The complexity of caring for patients with ruptured cerebral aneurysm: case studies.
Ruptured intracerebral aneurysm causes instantaneous neurologic chaos and is associated with high morbidity ad mortality. The event initiates a cascade of physiologic and structural changes that manifest themselves in a variety of clinical symptoms. The critical care team of nurses, physicians, and therapists must rapidly identify the cause; understand the pathology; and use advanced assessment techniques, medications, and interventions to stabilize the patient and to counter the horrendous effects of the injury. Interventions that include endovascular aneurysm coiling and cerebral angioplasty are providing new options for isolating the aneurysm and countering the effects of vasospasm. Through an integrated team approach, recovery from ruptured aneurysm will be maximized.


Pediatric psychopharmacology.
This paper reviews research in pediatric psychopharmacology over the past decade. The authors first discuss social, economic, and other influences on pediatric psychopharmacology research and prescribing patterns including changing models of childhood psychopathology, increased government funding, and changes in industry regulations. Definitions are offered for current research terminology including efficacy, effectiveness, and adverse events. Design trends and new approaches to outcome measurement are also presented. New data from the last 10 years of research is reviewed for each major class of psychotropic agents. Criteria for inclusion in the review are presented and include aspects of study design (placebo-controlled, large sample size), source of funding (government funded vs. industry), and vision (creative applications). Data for short-term efficacy, long-term efficacy, effectiveness, and safety and adverse events are discussed for each class of medication, although for many, there remains little empirical data. Findings for stimulants, selective serotonin reuptake inhibitors, neuroleptics, alpha-adrenergic agonists, mood stabilizers, buproprion, secretin, naltrexone, immune therapies, and natural supplements are all presented. Finally, the authors offer some speculations regarding the future of pediatric psychopharmacology research.


Heterogeneity in genetic disorders that affect the orofacies.
The diagnosis of genetic disorders is complicated by multiple genetic causes for the same or similar disorders, phenotypic similarities of different disorders, and environmental disorders that resemble genetic ones. The clinical geneticist is well versed in identifying genetic heterogeneity, and the extent of the clinical heterogeneity and phenocopies for diseases with which he or she deals regularly. Nonetheless, the expertise of clinical geneticists form other specialties of medicine or dentistry may be useful in documenting heterogeneity that otherwise may be overlooked. The examples presented here illustrate that heterogeneity is as important to the dentist who practices clinical genetics as it is to the physician-clinical geneticist, and that a consultation with a properly trained dentist may be a useful part of a protocol for the genetic evaluation.


Embryonic GABA(B) receptor blockade alters cell migration, adult hypothalamic structure, and anxiety- and depression-like behaviors sex specifically in mice.
Neurons of the paraventricular nucleus of the hypothalamus (PVN) regulate the hypothalamic- pituitary-adrenal (HPA) axis and the autonomic nervous system. Females lacking functional GABA(B) receptors because of a genetic disruption of the R1 subunit have altered cellular characteristics in and around the PVN at birth. The genetic disruption precluded appropriate assessments of physiology or behavior in adulthood. The current study was conducted to test the long term impact of a temporally restricting pharmacological blockade of the GABA(B) receptor to a 7-day critical period (E11-E17) during embryonic development. Experiments tested the role of GABA(B) receptor signaling in fetal development of the PVN and later adult capacities for adult stress related behaviors and physiology. In organotypic slices containing fetal PVN, there was a female specific, 52% increase in cell movement speeds with GABA(B) receptor antagonist treatment that was consistent with a sex-dependent lateral displacement of cells in vivo following 7 days of fetal exposure to GABA(B) receptor antagonist. Anxiety-like and depression-like behaviors, open-field activity, and HPA mediated responses to restraint stress were measured in adult offspring of mothers treated with GABA(B) receptor antagonist. Embryonic exposure to GABA(B) receptor antagonist resulted in reduced HPA axis activation following restraint stress and reduced depression-like behaviors. There was also increased anxiety-like behavior selectively in females and hyperactivity in males. A sex dependent response to disruptions of GABA(B) receptor signaling was identified for PVN formation and key aspects of physiology and behavior. These changes correspond to sex specific prevalence in similar human disorders, namely anxiety disorders and hyperactivity.


Genetic locus on MWF rat chromosome 6 affects kidney damage in response to L-NAME treatment in spontaneously hypertensive rats.
A major quantitative trait locus (QTL) on rat chromosome (RNO)6 was linked to albuminuria in Munich Wistar Frömter rats (MWF). We tested whether transfer of MWF RNO6 into the background of albuminuria-resistant spontaneously hypertensive rats (SHR) induces albuminuria in consomic SHR-6(MWF) animals. Male MWF, SHR, and SHR-6(MWF) were sham operated and treated between 6 and 24 wk of age with normal water (Sham) or with water containing 20 mg/l N(G)-nitro-L-arginine methyl ester (L-NAME) or unilaterally nephrectomized (Nx). Compared with SHR albuminuria was not increased in SHR-6(MWF) in both Sham and Nx groups. All animals survived the observation period in Sham and Nx groups, while premature mortality occurred from 12-14 wk on in L-NAME-treated SHR and SHR-6(MWF) compared with MWF L-NAME animals, in which survival was not affected (P < 0.005, respectively). Subsequent further analysis of L-NAME-treated animals at 12 wk of age showed significantly increased arterial blood pressures in both SHR and SHR-6(MWF) compared with control (P < 0.05), with higher levels in SHR compared with consomics (P < 0.05). However, L-NAME-treated consomic animals demonstrated increased albuminuria compared with SHR (12.7 +/- 3.5 vs. 0.8 +/- 0.2 mg/24 h; P < 0.05) and an induction of tubulointerstitial structural injury and expression of neutrophil gelatinase-associated lipocalin mRNA (P < 0.05 vs. other strains). Our study demonstrates that isolation of the RNO6 albuminuria QTL from the MWF background and transfer into SHR fails to induce an albuminuria phenotype during normal conditions or after nephron reduction. Moreover, our data indicate that genes on RNO6 contribute to the development of L-NAME-induced renal damage in the SHR strain.


Lean Mass Loss and Altered Muscular Aerobic Capacity after Bariatric Surgery.
Patients undergoing weight loss surgery do not improve their aerobic capacity or peak oxygen uptake (VO2peak) after bariatric surgery and some still complain about asthenia and/or breathlessness. We investigated the hypothesis that a post-surgery muscular limitation could impact the ventilatory response to exercise by evaluating the post-surgery changes in muscle mass, strength, and muscular aerobic capacity, measured by the first ventilatory threshold (VT). Thirteen patients with obesity were referred to our university exercise laboratory before and 6 months after bariatric surgery and were matched by sex, age, and height to healthy subjects with normal weight. All subjects underwent a clinical examination, blood sampling, and body composition assessment by dual-energy X-ray absorptiometry, respiratory and limb muscle strength assessments, and cardiopulmonary exercise testing on a cyclo-ergometer. Bariatric surgery resulted in a loss of 34% fat mass, 43% visceral adipose tissue, and 12% lean mass (LM) (p < 0.001). Absolute handgrip, quadriceps, or respiratory muscle strength remained unaffected, while quadriceps/handgrip strength relative to LM increased (p < 0.05). Absolute VO2peak or VO2peak/LM did not improve and the first VT was decreased after surgery (1.4 ± 0.3 vs. 1.1 ± 0.4 L min-1, p < 0.05) and correlated to the exercising LM (LM legs) (R = 0.84, p < 0.001). Although bariatric surgery has numerous beneficial effects, absolute VO2peak does not improve and the weight loss-induced LM reduction is associated to an altered muscular aerobic capacity, as reflected by an early VT triggering early exercise hyperventilation.


Ion-Pair Oligomerization of Chromogenic Triangulenium Cations with Cyanostar-Modified Anions That Controls Emission in Hierarchical Materials.
The hierarchical assembly of colored cationic molecules with receptor-modified counteranions can be used to control optical properties in materials. However, our knowledge of when the optical properties emerge in the hierarchical organization and the variety of cation-anion salts that are available to create these materials is limited. In this work, we extend the salts from small halides to large inorganic anions and determine how the structure coevolves with the emission properties using solution assemblies. We study the chromogenic trioxatriangulenium (TOTA+) cation and its coassembly with cyanostar (CS) macrocycles selected to modify tetrafluoroborate (BF4-) counteranions through formation of 2:1 sandwich complexes. In the solid state, the TOTA+ cation stacks in an alternating manner with the sandwich complexes producing new red-shifted emission and absorption bands. Critical to assigning the structural origin of the new optical features across the four levels of organization (1° → 4°) is the selection of specific solvents to produce and characterize different assemblies present in the hierarchical structure. A key species is the electrostatically stabilized ion pair between the TOTA+ cation and sandwich complex. The red-shifted features only emerge when the ion pairs oligomerize together into larger (TOTA·[CS2BF4])n assemblies. New electronic states emerge as a result of multiple copies of the TOTA+ making π-contact with cyanostar-anion complexes. Our findings and the ease with which the materials can be prepared as crystals and films by mixing the salt with a receptor provide a strong platform for the de novo design of new optical materials.


Community-acquired respiratory infections: spectrum of organisms and treatment.
The respiratory infections addressed in this paper include otitis media, sinusitis, and community-acquired pneumonia. The morbidity and mortality of respiratory infections are assessed from the American standpoint ; their worldwide significance is even greater. The emphasis is on specific diagnosis. Treatment options vary from country to country. Therapeutic decisions are usually easy once a specific etiologic organism is isolated. Since in many of these common respiratory infections a specific microorganism is not documented and empiric therapy is designed based on past clinical studies, resistance patterns need to be known for each country.


Safety and feasibility of percutaneous delivery of a novel circulatory assist device (CircuLite® SYNERGY®) in the swine model.
To demonstrate the feasibility and safety of percutaneous delivery of the novel inflow cannula of the CircuLite® SYNERGY® pocket Micro-pump via transseptal access in the swine model. After transseptal puncture, the inflow cannula system was advanced into the left atrium (LA) via the right external jugular vein and anchored onto the atrial septum under fluoroscopic and intracardiac echo guidance in 14 acute animals. Subsequently, chronic studies were performed to examine the long-term healing response to the cannula implantation with an artery-LA shunt (n=10) and overall safety of the Micro-pump components (n=6). Acute studies proved the concept of transcatheter delivery of the inflow cannula via superior venous access. The cannula tips were securely anchored in all chronic animals and appropriately endothelialised as early as two weeks. No thrombi or septal damage was observed. For the chronic pump group, device speed of 22,000 rpm (~2.0 L/min) was maintained without any adverse cardiac events. Plasma free haemoglobin assays confirmed the absence of clinically significant haemolysis. The transcatheter delivery of the inflow cannula via superior venous access to the LA is feasible and safe. This percutaneous delivery presents a significantly less invasive alternative to deliver partial circulatory support devices.


The atypical antipsychotic risperidone targets hypothalamic melanocortin 4 receptors to cause weight gain.
Atypical antipsychotics such as risperidone cause drug-induced metabolic syndrome. However, the underlying mechanisms remain largely unknown. Here, we report a new mouse model that reliably reproduces risperidone-induced weight gain, adiposity, and glucose intolerance. We found that risperidone treatment acutely altered energy balance in C57BL/6 mice and that hyperphagia accounted for most of the weight gain. Transcriptomic analyses in the hypothalamus of risperidone-fed mice revealed that risperidone treatment reduced the expression of Mc4r. Furthermore, Mc4r in Sim1 neurons was necessary for risperidone-induced hyperphagia and weight gain. Moreover, we found that the same pathway underlies the obesogenic effect of olanzapine-another commonly prescribed antipsychotic drug. Remarkably, whole-cell patch-clamp recording demonstrated that risperidone acutely inhibited the activity of hypothalamic Mc4r neurons via the opening of a postsynaptic potassium conductance. Finally, we showed that treatment with setmelanotide, an MC4R-specific agonist, mitigated hyperphagia and obesity in both risperidone- and olanzapine-fed mice.


Complications of cemented long-stem hip arthroplasty in metastatic bone disease revisited.
The literature suggests that a cemented long-stem femoral arthroplasty is associated with increased intraoperative and perioperative risks. Embolic events may precipitate cardiopulmonary complications and even death; by contrast, others have reported that the use of a cemented long-stem femoral arthroplasty in patients with metastatic bone disease is a safe procedure. Specifically, in this study, we sought to identify (1) intraoperative complications potentially attributable to the use of cemented long-stem femoral components, and (2) early postoperative complications potentially attributable to the use of cemented long-stem femoral components in patients having an arthroplasty for metastatic bone disease. In this study, we performed a retrospective chart review of 42 patients (44 arthroplasties), in which the same surgical technique was used. The primary outcome measure was perioperative complications, including intraoperative cement-associated desaturation, cement-associated hypotension, sympathomimetic administration, postoperative hypotension/desaturation, and death. In this series, 19% of the patients had cement-associated hypotension and sympathomimetics were administered to 48%. Two patients required prolonged intubation. One death occurred during hospitalization but there were no cardiopulmonary events. This study showed that some patients experienced postoperative desaturation, prolonged intubation, and increased use of sympathomimetics, however, these events were short-lived and did not result in patient mortality. Although there are significant risks to cemented long-stem femoral arthroplasty, it can be performed with a low risk of fatal cardiopulmonary complications and remains a surgical option when treating patients with metastatic bone disease. Level IV, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.


PECTIN METHYLESTERASE34 Contributes to Heat Tolerance through Its Role in Promoting Stomatal Movement.
Pectin, a major component of the primary cell wall, is synthesized in the Golgi apparatus and exported to the cell wall in a highly methylesterified form, then is partially demethylesterified by pectin methylesterases (PMEs; EC 184.108.40.206). PME activity on the status of pectin methylesterification profoundly affects the properties of pectin and, thereby, is critical for plant development and the plant defense response, although the roles of PMEs under heat stress (HS) are poorly understood. Functional genome annotation predicts that at least 66 potential PME genes are contained in Arabidopsis (Arabidopsis thaliana). Thermotolerance assays of PME gene T-DNA insertion lines revealed two null mutant alleles of PME34 (At3g49220) that both consistently showed reduced thermotolerance. Nevertheless, their impairment was independently associated with the expression of HS-responsive genes. It was also observed that PME34 transcription was induced by abscisic acid and highly expressed in guard cells. We showed that the PME34 mutation has a defect in the control of stomatal movement and greatly altered PME and polygalacturonase (EC 18.104.22.168) activity, resulting in a heat-sensitive phenotype. PME34 has a role in the regulation of transpiration through the control of the stomatal aperture due to its cell wall-modifying enzyme activity during the HS response. Hence, PME34 is required for regulating guard cell wall flexibility to mediate the heat response in Arabidopsis.


Identification and characterization of human MUS81-MMS4 structure-specific endonuclease.
Replication forks may stall when they reach a block on the DNA template such as DNA damage, and the recovery of such stalled replication forks plays a crucial role in the maintenance of genomic stability. Holliday junctions, which are X-shaped DNA structures, are formed at the stalled replication forks and can accumulate if they are not cleaved by structure-specific endonucleases. Recently, a novel nuclease involved in resolving Holliday junction-like structures, Mus81, has been reported in yeast and humans. MUS81 has sequence homology to another DNA nuclease, XPF, which, with its partner ERCC1, makes the 5' incision during nucleotide excision repair. MUS81 also has a binding partner named Mms4 in Saccharomyces cerevisiae and Eme1 in Schizosaccharomyces pombe, but no such partner was identified in human cells. Here, we report identification of the binding partner of human MUS81, which we designate hMMS4. Using immunoaffinity purification we show that hMUS81 or hMMS4 alone have no detectable nuclease activity, but that the hMUS81.hMMS4 complex is a structure-specific nuclease that is capable of resolving fork structures.


Dung beetles use the Milky Way for orientation.
When the moon is absent from the night sky, stars remain as celestial visual cues. Nonetheless, only birds, seals, and humans are known to use stars for orientation. African ball-rolling dung beetles exploit the sun, the moon, and the celestial polarization pattern to move along straight paths, away from the intense competition at the dung pile. Even on clear moonless nights, many beetles still manage to orientate along straight paths. This led us to hypothesize that dung beetles exploit the starry sky for orientation, a feat that has, to our knowledge, never been demonstrated in an insect. Here, we show that dung beetles transport their dung balls along straight paths under a starlit sky but lose this ability under overcast conditions. In a planetarium, the beetles orientate equally well when rolling under a full starlit sky as when only the Milky Way is present. The use of this bidirectional celestial cue for orientation has been proposed for vertebrates, spiders, and insects, but never proven. This finding represents the first convincing demonstration for the use of the starry sky for orientation in insects and provides the first documented use of the Milky Way for orientation in the animal kingdom.


Dietary inadequacies observed in homeless men visiting an emergency night shelter in Paris.
To assess the dietary intake and the nutritional status of homeless men. A night emergency shelter in Paris, France. Dietary survey (48-h) including alcohol intake and a questionnaire on age, duration of homelessness, smoking habits. Subjects were also weighed and measured. Ninety-seven men aged 18-72 years (mean 43.3), of whom 54% were homeless for more than 18 months, 82% were smokers and 53% were regular and/or excessive drinkers. The BMI distribution was shifted towards low values, the percentage of wasted persons being four times higher than in the reference population. The mean total energy intake was 2376 kcal and included a high and highly variable percentage of energy derived from alcohol (12.0% Among drinkers, the mean ethanol intake was 90 g and there was a significant negative correlation between ethanol and non-alcoholic energy intakes. The median intakes of potassium, calcium, zinc, vitamins B1, B2, and niacin were lower than European Population Reference Intakes but only the mean intake of vitamin B1 was significantly lower. Eighty percent of non-alcoholic energy was provided by charitable organisations. For most nutrients, the nutritional density of the shelter ration was not significantly different from the density of the foods purchased by the homeless. These data suggest that the content of some nutrients should be increased in existing food assistance programs for homeless people in France.


Probiotic therapy fails to improve gut permeability in a hapten model of colitis.
Studies in clinical and experimental inflammatory bowel disease (IBD) have shown disturbances in intestinal bacterial flora with an increase in potentially pathogenic and a decrease in protective organisms. It was hypothesized that Lactobacillus plantarum species 299 (LP299), a probiotic, would ameliorate colitis and improve intestinal permeability in experimental colitis. This study investigated the effect of LP299 in the trinitrobenzenesulfonic acid/ethanol (TNBS/E) rat model of colitis. Twelve week old male Wistar rats were randomized to receive rectal instillates of either TNBS/E (n = 48) or saline (n = 16). For the next 7 days the animals were gavaged with 2.5 ml of oat fibre suspension containing 10(9) colony forming units (CFU) of LP299 (LP299/OF), oat fibre suspension alone (OF) or no treatment. At the end of the experiment rats received radiolabelled polyethylene glycol and urine was collected for 24 h to assess permeability. Animals were then anaesthetized and colons were harvested for colon macroscopic scoring (CMS). TNBS/E per rectum resulted in a greater CMS (P < 0.001) and gut permeability (P = 0.006) than saline. Administration of LP299/OF or oat fibre alone did not result in a reduction in CMS or gut permeability when compared to colitic controls. LP299/OF, when administered after TNBS instillation, does not reduce the severity of colitis or improve gut permeability in this hapten model of colitis.


Association between hepatitis C virus antibodies and hepatocellular carcinoma in Taiwan.
In order to assess the association between antibodies to hepatitis C virus (anti-HCV) and hepatocellular carcinoma (HCC), as well as the interaction of anti-HCV with other HCC risk factors in Taiwan, a total of 127 pairs of newly diagnosed HCC patients and healthy community controls were studied. Case-control pairs were individually matched for age (+/- 3 years), sex, residence, and ethnicity. Serum samples from study subjects were examined for anti-HCV by enzyme immunoassays as well as hepatitis B surface antigen (HBsAg) and e antigen (HBeAg) by radioimmunoassays using commercial kits. The habits of cigarette smoking, alcohol drinking, and peanut consumption were obtained through standardized interviews according to a structured questionnaire. Both the anti-HCV as well as the carrier status of HBsAg and HBeAg were significantly associated with HCC showing a multivariate-adjusted odds ratio of 24.8 for carriers of HBsAg alone, 33.5 for carriers of both HBsAg and HBeAg, and 23.7 for those who were positive for anti-HCV. The population-attributable risk percentage was estimated as 3% for anti-HCV alone, 69% for HBsAg carrier status alone, and 6% for both anti-HCV and HBsAg in Taiwan. There were also synergistic effects on HCC development for anti-HCV with HBsAg carrier status, cigarette smoking, and habitual alcohol drinking.


Predictors of infection from dog bite wounds: which patients may benefit from prophylactic antibiotics?
To determine a current infection rate of dog bite wounds and predictors of wounds at risk for infection that may benefit from prophylactic antibiotics. A prospective multicentre observational study was conducted over 4.5 years. At the time of treatment Emergency Physicians completed a structured data form evaluating patient, wound and treatment characteristics of patients with dog bite wounds. Patients were followed up at 30 days to assess for infection. Predictor variables were analysed with univariate analysis, using either χ(2), parametric or nonparametric methods where appropriate. Significant variables and those with important interactions on univariate analysis were considered in a logistic regression (LR) analysis. 495 patients with dog bites were enrolled and 345 had complete follow-up. Eighteen patients (5.2%, 95% CI 3.1% to 8.1%) had bites that became infected. On univariate analysis, only puncture wounds were found to be significantly associated with infection RR 2.8 (95% CI 1.2 to 6.9). However, location and wound closure met criteria for entry into the model having important interactions; facial wounds had a higher risk of infection than anticipated but were also more likely to be closed (p < 0.0001). A LR model considering puncture wounds, wound closure and wound location found that puncture wounds (OR 4.1 [95% CI 1.4 to 11.7]) and wound closure (OR 3.1 [95% CI 1.03 to 9.0]) were independent predictors of infection. The incidence of infection in wounds that were not punctured or closed during treatment was only 2.6% (95% CI 0.7% to 6.5%). Puncture wounds or wounds closed during treatment are dog bite wounds at a high risk of infection and should be considered for treatment with prophylactic antibiotics.


Effects of alpha- and beta-adrenoceptor stimulation on 45Ca2+ efflux and insulin secretion from perfused rat islets.
Exposure to the beta 2-adrenoceptor agonist terbutaline resulted in a transient stimulation of 45Ca2+ efflux from 45Ca2+ preloaded rat islets perfused in 2 mM Ca2+ and 8.3 mM glucose. Concomitantly, an increase in insulin secretion occurred. Under the same experimental conditions, the alpha-adrenoceptor agonist noradrenaline promptly inhibited insulin release without any apparent influence on 45Ca2+ efflux. In contrast, in a medium containing 2 mM Ca2+ and a low glucose concentration (2.8 mM), terbutaline stimulated insulin secretion without any apparent effects on 45Ca2+ efflux. Noradrenaline had no effect on insulin secretion or 45Ca2+ efflux in this medium. When islets were perfused with 8.3 mM glucose in a Ca2+ deficient medium, with or without addition of the chelating agent EGTA, terbutaline induced a marginal stimulation of insulin secretion and a negligible stimulation of 45Ca2+ efflux. On the contrary, noradrenaline stimulated to an immediate and notable 45Ca2+ efflux in these Ca2+ deficient media. Noradrenaline also clearly inhibited insulin secretion, though less markedly and with a slower onset than in islets perfused in 2 mM Ca2+. When the islets were perfused in a Ca2+ deficient medium with 2.8 mM glucose, terbutaline had a slight insulin releasing effect, but stimulated 45Ca2+ efflux potently. Noradrenaline had no influence on insulin secretion but a weak stimulatory effect on 45Ca2+ efflux. The data suggest that the beta 2-adrenoceptor agonist terbutaline has the ability to stimulate insulin secretion in perfused rat islets, requiring extracellular Ca2+ for the full expression of its effects. These effects may be exerted through a Ca2+-Ca2+ exchange over the cell membrane and/or through cAMP and intracellular Ca2+ perturbations.(ABSTRACT TRUNCATED AT 250 WORDS)


Safety evaluation of the food enzyme alternansucrase from Leuconostoc citreum strain NRRL B-30894.
The food enzyme alternansucrase (sucrose:1,6(1,3)-α-d-glucan 6(3)-α-d-glucosyltransferase, EC 184.108.40.206) is produced with a non-genetically modified Leuconostoc citreum strain NRRL B-30894 by Cargill Incorporated. As a consequence of the absence of antimicrobial resistance genes identified in its genome, the production strain meets the criteria to qualify for the Qualified Presumption of Safety (QPS) approach to safety assessment. As no other concerns arising from the microbial source or from the manufacturing process have been identified, the Panel considers that toxicological tests are not needed for the assessment of this food enzyme. The alternansucrase food enzyme is intended to be used for the manufacture of α-d-glucan oligosaccharides as a sweetening agent. The purification processes applied to syrups produced from sucrose with alternansucrase are expected to largely remove the food enzyme. Any residual TOS remaining in the final product would consist of non-hazardous material. This is based on the QPS status of the production organism, the medium components and the identified material used in downstream processing. Consequently, the Panel decided that dietary exposure did not need to be calculated. Similarity of the amino acid sequence to those of known allergens was searched and no match was found. The Panel considered that, under the intended conditions of use, the risk of allergic sensitisation and elicitation reactions by dietary exposure cannot be excluded, but the likelihood for this to occur is considered to be low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.


The 100S ribosome: ribosomal hibernation induced by stress.
One of the most important cellular events in all organisms is protein synthesis (translation), which is catalyzed by ribosomes. The regulation of translational activity is dependent on the environmental situation of the cell. A decrease in overall translation under stress conditions is mainly accompanied by the formation of functionally inactive 100S ribosomes in bacteria. The 100S ribosome is a dimer of two 70S ribosomes that is formed through interactions between their 30S subunits. Two mechanisms of 100S ribosome formation are known: one involving ribosome modulation factor (RMF) and short hibernation promoting factor (HPF) in a part of Gammaproteobacteria including Escherichia coli, and the other involving only long HPF in the majority of bacteria. The expression of RMF is regulated by ppGpp and cyclic AMP-cAMP receptor protein (cAMP-CRP) induced by amino acid starvation and glucose depletion, respectively. When stress conditions are removed, the 100S ribosome immediately dissociates into the active 70S ribosomes by releasing RMF. The stage in the ribosome cycle at which the ribosome loses translational activity is referred to as 'Hibernation'. The lifetime of cells that cannot form 100S ribosomes by deletion of the rmf gene is shorter than that of parental cells under stress conditions in E. coli. This fact indicates that the interconversion system between active 70S ribosomes and inactive 100S ribosomes is an important survival strategy for bacteria.


A comparison of skeletal, cardiac, and smooth muscle actions of dantrolene sodium--a skeletal muscle relaxant.
Dantroline sodium, a skeletal muscle relaxant, has been proposed to inhibit the relase of Ca++ from the sarcoplasmic reticulum. Such a mechanism suggests that other muscle contractile systems operating with the same Ca++ denominator should also be affected by the drug. In the present studies dantrolene sodium effects on smooth, cardiac and skeletal muscle have been evaluated with in situ and in vitro techniques. In anesthetized dogs in situ skeletal muscle contractions were inhibitied in a dose-dependent manner, but cardiac muscle contractions were not. Effects on intestinal smooth muscle responses were highly variable and of short duration. In vitro, ED50 values were developed with dantrolene sodium (0.15-120 mg/l) in DMSO for each tissue. Skeletal muscle was the most sensitive (ED50 = 4.1 mg/l), cardiac muscle contractions were not inhibited by the drug and intestinal smooth muscle (ED50 = 59.0 mg/l) was approximately 1/14 as sensitive as skeletal muscle. It is concluded that skeletal muscle is uniquely sensitive to dantrolene sodium. A hypothesis for this specific action is offered.


Vascular endothelial growth factor up-regulates cyclooxygenase-2 expression in human endothelial cells.
We investigated the effects of vascular endothelial growth factor (VEGF) on cyclooxygenase-2 (COX-2) expression and prostaglandin E(2) (PGE(2)) synthesis in human microvascular endothelial cells (HMEC-1). Treatment of HMEC-1 with VEGF resulted in a dose- and time-dependent up-regulation of COX-2 mRNA and protein levels. This up-regulation was accompanied by a 1.6-fold increase in PGE(2) synthesis. Pretreatment of HMEC-1 with a selective COX-2 inhibitor, NS-398, abolished VEGF-induced PGE(2) synthesis, suggesting specific up-regulation of COX-2 activity by VEGF in HMEC-1. Transient transfection assays using deletion mutants of the human COX-2 promoter fused to the luciferase reporter gene indicated critical requirement of a regulatory region spanning -828/-123 bp for VEGF induction of COX-2 promoter activity in HMEC-1. Site-directed mutation analysis demonstrated that a GATA cis-acting element at -685/-680 bp was essential for VEGF- induced COX-2 promoter activity in HMEC-1. These observations are of particular importance given the recent demonstrations of critical requirement of COX-2 isoenzyme for tumor growth and angiogenesis.


Aldose reductase induced by hyperosmotic stress mediates cardiomyocyte apoptosis: differential effects of sorbitol and mannitol.
Cells adapt to hyperosmotic conditions by several mechanisms, including accumulation of sorbitol via induction of the polyol pathway. Failure to adapt to osmotic stress can result in apoptotic cell death. In the present study, we assessed the role of aldose reductase, the key enzyme of the polyol pathway, in cardiac myocyte apoptosis. Hyperosmotic stress, elicited by exposure of cultured rat cardiac myocytes to the nonpermeant solutes sorbitol and mannitol, caused identical cell shrinkage and adaptive hexose uptake stimulation. In contrast, only sorbitol induced the polyol pathway and triggered stress pathways as well as apoptosis-related signaling events. Sorbitol resulted in activation of the extracellular signal-regulated kinase (ERK), p54 c-Jun N-terminal kinase (JNK), and protein kinase B. Furthermore, sorbitol treatment resulting in induction and activation of aldose reductase, decreased expression of the antiapoptotic protein Bcl-xL, increased DNA fragmentation, and glutathione depletion. Apoptosis was attenuated by aldose reductase inhibition with zopolrestat and also by glutathione replenishment with N-acetylcysteine. In conclusion, our data show that hypertonic shrinkage of cardiac myocytes alone is not sufficient to induce cardiac myocyte apoptosis. Hyperosmolarity-induced cell death is sensitive to the nature of the osmolyte and requires induction of aldose reductase as well as a decrease in intracellular glutathione levels.


Systematic Review and Meta-Analysis on Using Acupressure to Promote the Health of Older Adults.
Acupressure is noninvasive, safe, and appropriate for use among older adults. However, there remains little evidence of the common elements that contribute to the effectiveness of acupressure in promoting the health of older adults. A systematic review using meta-analysis was designed to examine the effects of acupressure on the health promotion in older adults. Studies published between 2012 and 2017 were searched for in 11 electronic databases. Acupressure was highly effective for improving sleep quality and cognitive functioning (0.85, 95% confidence interval [CI] = [0.49, 1.22]; 1.23, 95% CI = [0.88, 1.59]). A slight to moderate effect was found in alleviating constipation (0.37, 95% CI = [0.03, 0.71]), and a moderate effect was found for alleviating pain and improving quality of life (0.71, 95% CI = [0.09, 1.32]; 0.59 95% CI = [0.36, 0.82]).


Tautomerism-Induced Cis-Trans Isomerization of Pyridylethenyl N-Confused Porphyrin.
Pyridylethenyl-substituted N-confused porphyrins (NCPs) were synthesized, and their cis-trans isomerization was studied. Among four possible isomers, trans-3H and cis-2H types of structures, of which aromaticity and absorption/emission properties differ largely, were isolated. The cis-isomer was largely stabilized by the intramolecular hydrogen bonding between the pyrrolic-NH and the pyridinic-N in the vicinity. The thermal cis-trans isomerization proceeded even at 30 °C, which was significantly accelerated by the pyridine added to the system. The kinetic studies revealed that the isomerization reaction was second-order and the activation energy of the thermal isomerization from cis to trans isomer was ΔG0⧧cis→trans = 35.7 kcal/mol at 298 K, which is significantly smaller than that of Ni complex (42.3 kcal/mol). An intermolecular proton transfer induced cis-trans isomerization mechanism was proposed.


Arabidopsis vegetative actin isoforms, AtACT2 and AtACT7, generate distinct filament arrays in living plant cells.
Flowering plants express multiple actin isoforms. Previous studies suggest that individual actin isoforms have specific functions; however, the subcellular localization of actin isoforms in plant cells remains obscure. Here, we transiently expressed and observed major Arabidopsis vegetative actin isoforms, AtACT2 and AtACT7, as fluorescent-fusion proteins. By optimizing the linker sequence between fluorescent protein and actin, we succeeded in observing filaments that contained these expressed actin isoforms fused with green fluorescent protein (GFP) in Arabidopsis protoplasts. Different colored fluorescent proteins fused with AtACT2 and AtACT7 and co-expressed in Nicotiana benthamiana mesophyll cells co-polymerized in a segregated manner along filaments. In epidermal cells, surprisingly, AtACT2 and AtACT7 tended to polymerize into different types of filaments. AtACT2 was incorporated into thinner filaments, whereas AtACT7 was incorporated into thick bundles. We conclude that different actin isoforms are capable of constructing unique filament arrays, depending on the cell type or tissue. Interestingly, staining patterns induced by two indirect actin filament probes, Lifeact and mTalin1, were different between filaments containing AtACT2 and those containing AtACT7. We suggest that filaments containing different actin isoforms bind specific actin-binding proteins in vivo, since the two probes comprise actin-binding domains from different actin-binding proteins.


Zebrafish heart regeneration: 15 years of discoveries.
Cardiovascular disease is the leading cause of death worldwide. Compared to other organs such as the liver, the adult human heart lacks the capacity to regenerate on a macroscopic scale after injury. As a result, myocardial infarctions are responsible for approximately half of all cardiovascular related deaths. In contrast, the zebrafish heart regenerates efficiently upon injury through robust myocardial proliferation. Therefore, deciphering the mechanisms that underlie the zebrafish heart's endogenous regenerative capacity represents an exciting avenue to identify novel therapeutic strategies for inducing regeneration of the human heart. This review provides a historical overview of adult zebrafish heart regeneration. We summarize 15 years of research, with a special focus on recent developments from this fascinating field. We discuss experimental findings that address fundamental questions of regeneration research. What is the origin of regenerated muscle? How is regeneration controlled from a genetic and molecular perspective? How do different cell types interact to achieve organ regeneration? Understanding natural models of heart regeneration will bring us closer to answering the ultimate question: how can we stimulate myocardial regeneration in humans?


Heparin thromboprophylaxis in medical-surgical critically ill patients: a systematic review and meta-analysis of randomized trials.
Venous thromboembolism prevention during critical illness is a widely used quality metric. The objective of this systematic review was to systematically review the efficacy and safety of heparin thromboprophylaxis in medical-surgical patients in the ICU. We searched EMBASE, MEDLINE, the Cochrane Controlled Trials Register, Clinicaltrials.gov, and personal files through May 2012. Randomized trials in adult medical-surgical ICU patients comparing any heparin (unfractionated heparin or low-molecular-weight heparin) with each other or no anticoagulant prophylaxis, evaluating deep vein thrombosis, pulmonary embolism, major bleeding, or mortality. Independently, in duplicate, we abstracted trial characteristics, outcomes, and risk of bias. Seven trials involved 7,226 patients. Any heparin thromboprophylaxis compared with placebo reduced rates of deep vein thrombosis (pooled risk ratio, 0.51 [95% CI, 0.41, 0.63]; p<0.0001; I=77%) and pulmonary embolism (risk ratio, 0.52 [95% CI, 0.28, 0.97]; p=0.04; I=0%) but not symptomatic deep vein thrombosis (risk ratio, 0.86 [95% CI, 0.59, 1.25]; p=0.43). Major bleeding (risk ratio, 0.82 [95% CI, 0.56, 1.21]; p=0.32; I=50%) and mortality (risk ratio, 0.89 [95% CI, 0.78, 1.02]; p=0.09; I=0%) rates were similar. Compared with unfractionated heparin, low-molecular-weight heparin reduced rates of pulmonary embolism (risk ratio, 0.62 [95% CI, 0.39, 1.00]; p=0.05; I=53%) and symptomatic pulmonary embolism (risk ratio, 0.58 [95% CI, 0.34, 0.97]; p=0.04) but not deep vein thrombosis (risk ratio, 0.90 [95% CI, 0.74, 1.08]; p=0.26; I=0%), symptomatic deep vein thrombosis (risk ratio, 0.87 [95% CI, 0.60, 1.25]; p=0.44; I=0%), major bleeding (risk ratio, 0.97 [95% CI, 0.75, 1.26]; p=0.83; I=0%), or mortality (risk ratio, 0.93 [95% CI, 0.82, 1.04]; p=0.20; I=31%). Trial evidence to date suggests that any type of heparin thromboprophylaxis decreases deep vein thrombosis and pulmonary embolism in medical-surgical critically ill patients, and low-molecular-weight heparin compared with bid unfractionated heparin decreases pulmonary embolism and symptomatic pulmonary embolism. Major bleeding and mortality rates do not appear to be significantly influenced by heparin thromboprophylaxis in the ICU setting. Trial methodology, indirectness, and the heterogeneity and imprecision of some results temper inferences from this literature.


Proline Precursors and Collagen Synthesis: Biochemical Challenges of Nutrient Supplementation and Wound Healing.
Wound healing is a complex process marked by highly coordinated immune fluxes into an area of tissue injury; these are required for re-establishment of normal tissue integrity. Along with this cascade of cellular players, wound healing also requires coordinated flux through a number of biochemical pathways, leading to synthesis of collagen and recycling or removal of damaged tissues. The availability of nutrients, especially amino acids, is critical for wound healing, and enteral supplementation has been intensely studied as a potential mechanism to augment wound healing-either by increasing tensile strength, decreasing healing time, or both. From a practical standpoint, although enteral nutrient supplementation may seem like a reasonable strategy to augment healing, a number of biochemical and physiologic barriers exist that limit this strategy. In this critical review, the physiology of enteral amino acid metabolism and supplementation and challenges therein are discussed in the context of splanchnic physiology and biochemistry. Additionally, a review of studies examining various methods of amino acid supplementation and the associated effects on wound outcomes are discussed.


Brain potentials predict substance abuse treatment completion in a prison sample.
National estimates suggest that up to 80% of prison inmates meet diagnostic criteria for a substance use disorder. Because more substance abuse treatment while incarcerated is associated with better post-release outcomes, including a reduced risk of accidental overdose death, the stakes are high in developing novel predictors of substance abuse treatment completion in inmate populations. Using electroencephalography (EEG), this study investigated stimulus-locked ERP components elicited by distractor stimuli in three tasks (VO-Distinct, VO-Repeated, Go/NoGo) as a predictor of treatment discontinuation in a sample of male and female prison inmates. We predicted that those who discontinued treatment early would exhibit a less positive P3a amplitude elicited by distractor stimuli. Our predictions regarding ERP components were partially supported. Those who discontinued treatment early exhibited a less positive P3a amplitude and a less positive PC4 in the VO-D task. In the VO-R task, however, those who discontinued treatment early exhibited a more negative N200 amplitude rather than the hypothesized less positive P3a amplitude. The discontinuation group also displayed less positive PC4 amplitude. Surprisingly, there were no time-domain or principle component differences among the groups in the Go/NoGo task. Support Vector Machine (SVM) models of the three tasks accurately classified individuals who discontinued treatment with the best model accurately classifying 75% of inmates. PCA techniques were more sensitive in differentiating groups than the classic time-domain windowed approach. Our pattern of findings are consistent with the context-updating theory of P300 and may help identify subtypes of ultrahigh-risk substance abusers who need specialized treatment programs.


Meta-analysis of major depressive disorder relapse and recurrence with second-generation antidepressants.
This meta-analysis reviewed data on the efficacy and effectiveness of second-generation antidepressants for preventing major depression relapse and recurrence during continuation and maintenance phases of treatment, respectively. MEDLINE, EMBASE, and PsycINFO, the Cochrane Library, and International Pharmaceutical Abstracts were searched for the period of January 1980 through April 2007 for reviews, randomized controlled trials, meta-analyses, and observational studies on the topic. Two persons independently reviewed abstracts and full-text articles using a structured data abstraction form to ensure consistency in appraisal and data extraction. Four comparative trials and 23 placebo-controlled trials that addressed relapse or recurrence prevention were included. Results of comparative trials have not demonstrated statistically significant differences between duloxetine and paroxetine, fluoxetine and sertraline, fluvoxamine and sertraline, and trazodone and venlafaxine. Pooled data for the class of second-generation antidepressants compared with placebo suggested a relatively large effect size that persists over time. For preventing both relapse and recurrence, the number of patients needed to treat is five (95% confidence interval of 4 to 6). Differences in the length of open-label treatment before randomization, drug type, and trial duration did not affect pooled estimates of relapse rates. Across all trials, 7% of patients randomly assigned to receive active treatment and 5% of patients randomly assigned to receive a placebo discontinued treatment because of adverse events. This review demonstrates the overall benefits of continuation- and maintenance-phase treatment of major depression with second-generation antidepressants and emphasizes the need for additional studies of comparative differences among drugs.


Celecoxib inhibits prostate cancer growth: evidence of a cyclooxygenase-2-independent mechanism.
Selective cyclooxygenase-2 (COX-2) inhibitors may suppress carcinogenesis by both COX-2-dependent and COX-2-independent mechanisms. The primary purpose of this study was to evaluate whether celecoxib or rofecoxib, two widely used selective COX-2 inhibitors, possess COX-2-independent antitumor activity. PC3 and LNCaP human prostate cancer cell lines were used to investigate the growth inhibitory effects of selective COX-2 inhibitors in vitro. To complement these studies, we evaluated the effect of celecoxib on the growth of PC3 xenografts. COX-1 but not COX-2 was detected in PC3 and LNCaP cells. Clinically achievable concentrations (2.5-5.0 micromol/L) of celecoxib inhibited the growth of both cell lines in vitro, whereas rofecoxib had no effect over the same concentration range. Celecoxib inhibited cell growth by inducing a G(1) cell cycle block and reducing DNA synthesis. Treatment with celecoxib also led to dose-dependent inhibition of PC3 xenograft growth without causing a reduction in intratumor prostaglandin E(2). Inhibition of tumor growth occurred at concentrations (2.37-5.70 micromol/L) of celecoxib in plasma that were comparable with the concentrations required to inhibit cell growth in vitro. The highest dose of celecoxib led to a 52% reduction in tumor volume and an approximately 50% decrease in both cell proliferation and microvessel density. Treatment with celecoxib caused a marked decrease in amounts of cyclin D1 both in vitro and in vivo. Two clinically available selective COX-2 inhibitors possess different COX-2-independent anticancer properties. The anticancer activity of celecoxib may reflect COX-2-independent in addition to COX-2-dependent effects.


Effect of supplemental niacin or niacinamide and soybean source on ruminal bacterial fermentation in continuous culture.
Effects of niacin or niacinamide in diets containing either soybean meal, raw whole soybeans or whole soybeans extruded at 132 and 149 C on ruminal bacterial fermentation were examined with a dual-flow continuous culture system. In Exp. 1, soybean sources each provided 50% of total crude protein in diets comprised of 52% concentrate mix, 36% corn silage and 12% alfalfa hay (dry-matter basis). Each diet was supplemented with 0 or 100 mg/kg niacin. Niacin supplementation increased (P less than .05) total nonstructural carbohydrate digestibility and lowered (P less than .05) butyrate concentration. There was also an increase (P less than .10) in amino acid effluent flow from 8,413.3 to 8,665.3 mg/d with addition of niacin to the diet. In Exp. 2, diets were supplemented with 0 or 100 mg/kg of niacin or niacinamide. The total mixed diet was comprised of 60% concentrate mix, 20% corn silage and 20% alfalfa hay (dry matter basis). Acid detergent fiber and cellulose digestibilities and total amino acid effluent flow were higher (P less than .10) with niacinamide supplementation. Niacin or niacinamide had no effect on dry matter and organic matter digestibilities, ammonia-N, total VFA concentration or crude protein degradation. Contrary to results found in other studies, niacin or niacinamide supplementation had no effect on bacterial protein synthesis.


Modulation of eDNA release and degradation affects Staphylococcus aureus biofilm maturation.
Recent studies have demonstrated a role for Staphylococcus aureus cidA-mediated cell lysis and genomic DNA release in biofilm adherence. The current study extends these findings by examining both temporal and additional genetic factors involved in the control of genomic DNA release and degradation during biofilm maturation. Cell lysis and DNA release were found to be critical for biofilm attachment during the initial stages of development and the released DNA (eDNA) remained an important matrix component during biofilm maturation. This study also revealed that an lrgAB mutant exhibits increased biofilm adherence and matrix-associated eDNA consistent with its proposed role as an inhibitor of cidA-mediated lysis. In flow-cell assays, both cid and lrg mutations had dramatic effects on biofilm maturation and tower formation. Finally, staphylococcal thermonuclease was shown to be involved in biofilm development as a nuc mutant formed a thicker biofilm containing increased levels of matrix-associated eDNA. Together, these findings suggest a model in which the opposing activities of the cid and lrg gene products control cell lysis and genomic DNA release during biofilm development, while staphylococcal thermonuclease functions to degrade the eDNA, possibly as a means to promote biofilm dispersal.


Water-soluble triazole chitin derivative and its based nanoparticles: Synthesis, characterization, catalytic and antibacterial properties.
In this work, we treated chitin with 2-(azidomethyl)oxirane and successfully involved the resultant azido chitin derivatives in the ultrasound-assisted Cu(I)-catalyzed azido-alkyne click (CuAAC) reaction with propargylic ester of N,N,N-trimethyl glycine. Thus, we obtained novel water-soluble triazole chitin derivatives. The triazole chitin derivatives and their nanoparticles are characterized by a high in vitro antibacterial activity, which is the same or even higher than that of commercial antibiotics ampicillin and gentamicin. The obtained derivatives are non-toxic. Moreover, the obtained water-soluble polymers are highly efficient green catalysts for the aldol reaction in green solvent water. The catalysts can be easily extracted from the reaction mixture by its precipitation with green solvent ethanol followed by centrifugation and they can be reused at least 10 times.


Cost-related medication nonadherence among beneficiaries with depression following Medicare Part D.
Cost-related medication nonadherence (CRN) was problematic for Medicare beneficiaries with depressive symptoms before Medicare Part D. To estimate changes in CRN and forgoing basic needs to pay for drugs among Medicare beneficiaries with and without depressive symptoms following Part D implementation. The authors compared changes in outcomes between 2005 and 2006 before and after Part D with changes between 2004 and 2005 using logistic regression to control for demographic characteristics, health status, and historical trends. The community-dwelling sample of the Medicare Current Beneficiary Survey (N = 24,234). Self-reports of CRN (skipping or reducing doses and not obtaining prescriptions) and spending less on basic needs to afford medicines. The unadjusted annual prevalence of CRN among beneficiaries with depressive symptoms was 27% (2004), 27% (2005), and 24% (2006), compared with 13%, 12%, and 9% among beneficiaries without depressive symptoms. The annual prevalence of spending less on basic needs was 22% (2004), 23% (2005), and 19% (2006), compared with 8%, 9%, and 5% among beneficiaries without depressive symptoms. Controlling for historical changes and demographic characteristics, CRN did not decline among beneficiaries with depressive symptoms compared with beneficiaries without depressive symptoms (ratio of Part D changes 0.98; 95% confidence interval [CI], 0.73-1.32). Respondents with depressive symptoms seemed less likely to spend less on basic needs compared with individuals without depressive symptoms (0.70; 95% CI, 0.49-1.01); however, this difference was not statistically significant. Despite a Medicare Part D goal to improve medication adherence among mentally ill beneficiaries, the disparity in economic access to medications between beneficiaries with and without depressive symptoms did not improve after the start of Part D.


Enzymes (beta-glucanase and arabinoxylanase) and/or sepiolite supplementation and the nutritive value of maize-barley-wheat based diets for broiler chickens.
1. Two experiments were conducted to study the effects of crude enzyme preparations (beta-glucanase and arabinoxylanase) and/or 20 g/kg Sepiolite (Exal) on the performance and nutrient digestion of broiler chickens fed on maize-barley-wheat based diets. 2. In experiment 1, enzymes improved daily bodyweight gain (by 14%; P<0.001) and food:gain ratios (8%; P<0.001). Sepiolite improved bodyweight gain on the diets not supplemented simultaneously with enzymes (by 6% in 21-d-old chickens, P<0.05) but reduced it for enzymes-supplemeented diets. Changes in productive perfiormance with both additives were associated with changes in diet digestibility and nitrogen balance. 3. In experiment 2, enzyme supplementation reduced viscosity in jejunum and ileum and the mean retention time of digesta in the gut. Sepiolite inclusion significantly reduced the viscosity of jejunum digesta and modified the retention times of digesta in the gut, depending upon whether enzymes had been added. There was a decreased retention time without enzymes but an increase with enzyme supplementation. 4. Although different mechanisms are presumed for enzymes and sepiolite, both seem to counteract the negative effects of soluble, non-starch polysaccharides (NSP) in the diet by modifying jejunal viscosity and improving organic matter digestibility.


Serum alpha 1-acid glycoprotein and interleukin-8 elevations in felines with localized and metastatic tumors.
This study aimed to investigate the expression of acute phase proteins and plasma cytokines in cats with various tumor types and varying metastatic statuses. 5 clinically healthy cats and 22 cats with neoplastic disease that underwent CT imaging before treatment were enrolled. Patients were grouped based on their tumor types and metastatic status. Blood samples were collected from all cats for general blood analyses before they underwent CT imaging. The remaining plasma sample was frozen for subsequent alpha 1-acid glycoprotein (AGP), serum amyloid A (SAA), and feline cytokine panel measurements. These results were compared with those of healthy cats as well as between metastatic status and tumor types. Only 4 cats (18%) exhibited elevated SAA levels, whereas 16 (73%) showed elevated AGP levels. AGP was significantly increased in cats with tumors (P = .016), while SAA was not. Only IL-8 showed a significant difference (P = .002) between cats with primary tumors and those with radiologically suspected tumor metastasis. While AGP is a more prominent biomarker than SAA in cats with tumors, a significant elevation of AGP and SAA levels in association with metastasis and specific tumor types could not be identified. Alternatively, further investigation is warranted to evaluate the potential significance of IL-8 in tumor progression and metastasis.


The very limited usefulness of skin testing with penicilloyl-polylysine and the minor determinant mixture in evaluating nonimmediate reactions to penicillins.
The contribution of skin testing with penicilloyl-polylysine (PPL) and the minor determinant mixture (MDM) to the diagnosis of hypersensitivity reactions to penicillins differs greatly according to the type of reaction: immediate (occurring within 1 h after the last drug administration) or nonimmediate (occurring more than 1 h after the last drug administration). To assess the contribution of skin testing with PPL and MDM to the diagnosis of nonimmediate reactions to penicillins. We evaluated 162 adults who had had 232 nonimmediate reactions to penicillins, mostly aminopenicillins, and presented positive skin and/or patch tests to one or more penicillin reagents: PPL, MDM, benzylpenicillin, ampicillin, and amoxicillin, as well as any responsible penicillins. A total of 157 subjects (96.9%) displayed patch-test and/or delayed-reading intradermal-test positivity to penicillin reagents, which indicates a cell-mediated hypersensitivity; six of them also presented immediate-reading skin-test positivities. All 157 patients with a cell-mediated hypersensitivity were positive to the responsible penicillins (parent drugs); 16 of them also displayed delayed-reading intradermal-test positivity to MDM. Five (3.1%) of the 162 patients displayed only immediate-reading skin-test positivity (four to PPL and one to amoxicillin). Overall, 158 subjects (97.5%) presented positive responses to the responsible penicillins, while only 9 (5.5%) and 17 (10.5%) were positive to PPL and MDM, respectively. The contribution of skin testing with PPL and MDM in diagnosing nonimmediate hypersensitivity reactions to penicillins, especially cell-mediated ones, is very limited. This finding could be useful at a time when PPL and MDM are not available in all countries.