Cancer-associated thrombosis: an overview.
Venous thromboembolism (VTE) is a common complication in patients with malignant disease. Emerging data have enhanced our understanding of cancer-associated thrombosis, a major cause of morbidity and mortality in patients with cancer. In addition to VTE, arterial occlusion with stroke and anginal symptoms is relatively common among cancer patients, and is possibly related to genetic predisposition. Several risk factors for developing venous thrombosis usually coexist in cancer patients including surgery, hospital admissions and immobilization, the presence of an indwelling central catheter, chemotherapy, use of erythropoiesis-stimulating agents (ESAs) and new molecular-targeted therapies such as antiangiogenic agents. Effective prophylaxis and treatment of VTE reduced morbidity and mortality, and improved quality of life. Low-molecular-weight heparin (LMWH) is preferred as an effective and safe means for prophylaxis and treatment of VTE. It has largely replaced unfractionated heparin (UFH) and vitamin K antagonists (VKAs). Recently, the development of novel oral anticoagulants (NOACs) that directly inhibit factor Xa or thrombin is a milestone achievement in the prevention and treatment of VTE. This review will focus on the epidemiology and pathophysiology of cancer-associated thrombosis, risk factors, and new predictive biomarkers for VTE as well as discuss novel prevention and management regimens of VTE in cancer according to published guidelines.


Medium-term follow-up of 149 mobile-bearing total knee arthroplasties and evaluation of prognostic factors influencing outcomes.
To evaluate the medium-term outcomes of a posterior-stabilized mobile-bearing total knee arthroplasty (PS-MB-TKA) and the role of different prognostic factors. Patients indicated for a primary cemented PS-MB-TKA between 2002 and 2010 were included and prospectively evaluated using the Knee Society Scoring System (KSS) and the Hospital for Special Surgery (HSS) knee scores. The Knee Society Roentgenographic Evaluation form was used for the radiological evaluation. Different variables were collected and divided into patient- and surgery-related. Logistic regression was used to analyze the correlation between these variables and implants outcomes and survivorship. In total, 149 cases were included (67.8% female, average age 70.4 years, SD ±9.4). The patella was resurfaced in 12.1% of the cases. All the implants were cemented. The average follow-up was 87.3 months (SD ±21.2). Postoperatively, there was a statistically significant improvement in all the scores. The cumulative survival was 96.2% (SD ±0.02%). At the regression analysis, female gender was associated to worse satisfaction KSS (OR = 0.26), functional KSS (OR = 0.22), and HSS (OR = 0.37) scores. Patellar resurfacing and subsequent contralateral procedures were associated to better functional KSS score (OR = 4.13, OR = 2.21), as well as varus preoperative alignment (OR = 2.12). On contrary, valgus preoperative alignment was associated to worse objective KSS score (OR = 0.23). No variables were correlated to failure or presence of radiolucent lines. Good medium-term outcomes were obtained using PS-MB-TKA, with a cumulative survivorship of 96.5%. Female gender and valgus preoperative alignment were associated to worse objective and subjective outcomes. Conversely, patellar replacement, subsequent contralateral TKA, and varus preoperative alignment were associated to better functional outcomes.


Synthesis and Structural Revision of the Fungal Tetramic Acid Metabolite Spiroscytalin.
Spiroscytalin, a natural 3-spirotetramic acid of hitherto uncertain absolute configuration, was synthesized for the first time by a one-pot Knoevenagel-IMDA reaction of an l-phenylalanine-derived tetramic acid and (R)-2-methyl-deca-6E,8E-dienal. Its absolute configuration was assigned by the known configurations of the starting compounds and by NOESY correlations. Its identity with the natural isolate was proved by the comparison of the NMR and circular dichroism spectra and of the specific optical rotations. Its absolute configuration (3R,5S,6S,7R,11S,14R) is enantiomeric to that originally proposed by the isolating group. This natural isomer of spiroscytalin showed moderate activity against Candida albicans and good activity against an export-deficient mutant of Escherichia coli.


Temperature-Independent Dielectric Constant in CsPbBr3 Nanocrystals Revealed by Linear Absorption Spectroscopy.
Fundamental photophysical behavior in CsPbBr3 nanocrystals (NCs), especially at low temperatures, is under active investigation. While many studies have reported temperature-dependent photoluminescence, comparatively few have focused on understanding the temperature-dependent absorption spectrum. Here, we report the temperature-dependent (35-300 K) absorption and photoluminescence spectra of zwitterionic ligand-capped CsPbBr3 NCs with four different edge lengths (d = 4.9, 7.2, 8.1, and 13.2 nm). The two lowest-energy excitonic transitions are quantitatively modeled over the full temperature range within the effective mass approximation considering the quasi-cubic NC shape and nonparabolicity of the electronic bands. Significantly, we find that the effective dielectric constant determined from the best fit model parameters is independent of temperature. Moreover, we observe a temperature-dependent Stokes shift that saturates at a finite value of Δ ≈ 10 meV at low temperatures for d = 7.2 nm NCs, which is absent in bulk CsPbBr3 films. Overall, these observations highlight differences between the temperature-dependent dielectric behavior of NC and bulk perovskites and point to the need for a more unified theoretical understanding of absorption and emission in halide perovskites.


Impact of proctectomy on continence and sexual function in women.
Whether treating a patient with colorectal cancer, or inflammatory bowel disease, or a variety of other gastrointestinal ailments, gastroenterologists sometimes need to enlist the help of colorectal surgeons to treat their patients. Surgical resection of the rectum is a frequently preformed procedure that has changed significantly over the last century. We have progressed from the early twentieth century, when removal of the rectum and anus with a permanent colostomy was a revolutionary and life-saving treatment for rectal cancer, to the present era of rectal resection and multiple, complex options for its reconstruction. Extensive knowledge of the pelvic anatomy is necessary in order for surgeons to preserve pelvic function while excising diseased tissue. Pelvic surgery poses unique challenges to patients, and proctectomy can drastically affect a woman's continence, sexual function, and fertility. It is imperative for gastroenterologists to understand how proctectomy can affect their patient's quality of life, independent of their disease state.


[Influential factors of water evaporation from burn wound].
To determine various influential factors of water evaporation from burn wound, we scalded 120 rats and divided them randomly into 12 groups. The rate of evaporation was studied under different temperatures and moistures. The experimental results showed that high temperature and low moisture were beneficial to the treatment of burn wound. Escharectomy, skin grafting and film forming agents could reduce evaporation. Azone could change the permeability of the skin and accelerate water evaporation.


Tezosentan inhibits both equinatoxin II and endotelin-1 induced contractions of isolated porcine coronary artery in a similar way.
In the present study we examined the endothelium-dependent mechanism in the constriction of the isolated porcine coronary artery induced by Equinatoxin II (EqT II). EqT II is a polypeptide isolated from the sea anemone (Actinia equina, L.). Contractions induced by endothelin-1 (ET-1) were compared with the contractions induced by EqT II. The force of contraction induced by 100 nM EqT II reached only 30% of the force of contraction induced by 100 nM ET-1. EC50 for ET-1 was 5.14 nM, and for EqT II 101.1 nM. The effects of tezosentan, an endothelin ETA/B receptor antagonist, on contractions induced by either ET-1 or EqT II were compared. Tezosentan inhibited both ET-1 and, to a lesser extent, EqT II-induced contractions of isolated porcine coronary artery. Our present results confirm the involvement of endothelium in the EqT II-induced contractions of coronary arteries. The mode of action of tezosentan upon EqT II-induced contractions indicate that besides its pore-forming effect in the membranes, endothelium, and specifically endothelin-dependent mechanisms, are very important components of the toxin constrictory effects.


Singlet oxygen induces predominantly G to T transversions on a single-stranded shuttle vector replicated in monkey cells.
To elucidate the mechanisms of mutagenesis by singlet oxygen DNA damage in mammalian cells, a SV40-derived single-stranded shuttle vector was exposed to the water soluble endoperoxide 3,3'-(1,4-naphthylidene) dipropionate (NDPO2). The damaged vector was transfected into monkey COS7 cells and the plasmid progeny exhibited up to 10 fold increase on the mutation frequency in the supF target gene, when compared to untreated vector. The sequence in the supF locus of such mutants revealed that singlet oxygen-induced mutagenesis in single-stranded vector is significantly different from spontaneous mutagenesis. Among the base substitutions, most of the mutations involved deoxyguanosines, being G to T transversions the predominant type of change. The data indicate that mutagenesis by singlet oxygen in mammalian cells may be generated by an error prone bypass of damaged deoxyguanosines at the template DNA.


Neutron diffraction studies of U4O9: comparison with EXAFS results.
Conradson et al. have analyzed X-ray absorption fine-structure spectra of the UO2-U4O9 system and concluded that oxygen atoms are incorporated in U4O9 as oxo groups with U-O distances in the range 1.72-1.76 A. They also found that the uranium sublattice consists of an ordered portion and an additional 'spectroscopically silent' glassy portion. We have carried out studies of powdered U4O9 by neutron diffraction which contradict these conclusions from EXAFS measurements. Our analysis shows that there are no U-O bonds shorter than 2.2 A and that U4O9 is crystallographically ordered with no evidence of a glassy structure.


A sensitive detection of T4 polynucleotide kinase activity based on β-cyclodextrin polymer enhanced fluorescence combined with an exonuclease reaction.
A strategy for T4 polynucleotide kinase activity detection was proposed based on a β-cyclodextrin polymer (polyβ-CD) and an exonuclease reaction. The fluorescence of pyrene enhanced by more than 10 times in the presence of polyβ-CD, and a simple detection of T4 PNK was achieved with a detection limit of 0.02 units per mL.


Single fibre electromyographic studies in myasthenia gravis with repetitive nerve stimulation.
A method is described for repetitive stimulation studies in myasthenia gravis using submaximal stimulation and single muscle fibre recording techniques. It was found that there were no impulse blockings due to neuromuscular transmission factors in normal subjects with 2 Hz stimulation, although there was a decrease or increase in the number of potentials which was caused by axonal stimulation factors. In myasthenia gravis a pathological picture was obtained, consisting of impulse blockings and facilitation at this rate in all of the eight patients studied, even those with only the ocular form of myasthenia and without surface decrement in the ADM. This technique allows study of both the minimally involved motor endplates and those with pronounced neuromuscular disturbances.


Avulsion of the left renal artery following blunt abdominal trauma in a dog.
A two-year-old, male, crossbreed dog was presented three days after being involved in a motor vehicle accident. Survey radiographs showed multiple pelvic fractures and poor intraperitoneal and retroperitoneal contrast. Ultrasound indicated the left kidney to be hypoperfused, and a thrombus was visible at the origin of the left renal artery. Ultrasound-guided fine needle aspiration confirmed that free fluid visible in the retroperitoneal and peritoneal spaces was blood. No improvement was seen in the renal perfusion over a 43 hour period, and the intestinal hypomotility worsened over this time. The haemoperitoneum and the haemoretroperitoneum both resolved ultrasonographically within this 43 hour period. Surgery confirmed an avulsion of the left renal artery approximately 10 mm from its origin on the aorta and an avulsion of the left ureter at the ureteropelvic junction. An ureteronephrectomy was performed on the left kidney and the dog recovered uneventfully.


Reticulin antibodies in patients with coeliac disease and their relatives.
The sera of 69 index coeliac patients, 121 of their first-degree relatives, and 104 controls were screened for the presence of reticulin antibodies. Among the untreated coeliac patients 75% of adults and 93% of children had reticulin antibody in their serum. Reticulin antibody was not present in any adequately treated coeliac patient. Of the first-degree relatives, 21 were reticulin antibody positive; 17 of these were biopsied and 12 were shown to have coeliac disease. Sixty-five of the coeliac relatives who did not have reticulin antibodies in their sera were biopsied and two had coeliac disease. Of the 68 relatives and 63 controls with normal biopsies, five of the relatives and four of the controls were reticulin antibody positive.


Ketoconazole resistant Candida albicans is sensitive to a wireless electroceutical wound care dressing.
Wireless electroceutical dressing (WED) fabric kills bacteria and disrupts bacterial biofilm. This work tested, comparing with standard of care topical antibiotic ketoconazole, whether the weak electric field generated by WED is effective to manage infection caused by ketoconazole-resistant yeast Candida albicans. WED inhibited Candida albicans biofilm formation and planktonic growth. Unlike ketoconazole, WED inhibited yeast to hyphal transition and downregulated EAP1 curbing cell attachment. In response to WED-dependent down-regulation of biofilm-forming BRG1 and ROB1, BCR1 expression was markedly induced in what seems to be a futile compensatory response. WED induced NRG1 and TUP1, negative regulators of filamentation; it down-regulated EFG1, a positive regulator of hyphal pathway. Consistent with the anti-hyphal properties of WED, the expression of ALS3 and HWP1 were diminished. Ketoconazole failed to reproduce the effects of WED on NRG1, TUP1 and EFG1. WED blunted efflux pump activity; this effect was in direct contrast to that of ketoconazole. WED exposure compromised cellular metabolism. In the presence of ketoconazole, the effect was synergistic. Unlike ketoconazole, WED caused membrane depolarization, changes in cell wall composition and loss of membrane integrity. This work presents first evidence that weak electric field is useful in managing pathogens which are otherwise known to be antibiotic resistant.


Prosthetic management of an extensive maxillary alveolar defect with an implant-supported restoration.
Despite the recent developments in peri-implant surgical regenerative procedures, re-establishing the hard and soft tissue contour is still a challenge in cases with severe ridge deficiency. It becomes more difficult when incorrectly placed implants cause screw connections to come out onto the labial surfaces of the teeth. A two-part maxillary implant supported fixed restoration was constructed. The first part was consisted of a screw retained sub-structure that replaced gingival portions of the deficient maxilla and the second part was a cement retained super-structure that reconstructed the anatomical crowns of the lost teeth. In this way awkwardly placed implants did not interfere with the desired esthetic result. Another great advantage was that the alterations or repairs on cemented crowns can easily be carried out without compromising the entire construction.


Semi-permeable coatings fabricated from comb-polymers efficiently protect proteins in vivo.
In comparison to neutral linear polymers, functional and architecturally complex (that is, non-linear) polymers offer distinct opportunities for enhancing the properties and performance of therapeutic proteins. However, understanding how to harness these parameters is challenging, and studies that capitalize on them in vivo are scarce. Here we present an in vivo demonstration that modification of a protein with a polymer of appropriate architecture can impart low immunogenicity, with a commensurably low loss of therapeutic activity. These combined properties are inaccessible by conventional strategies using linear polymers. For the model protein L-asparaginase, a comb-polymer bio-conjugate significantly outperformed the linear polymer control in terms of lower immune response and more sustained bioactivity. The semi-permeability characteristics of the coatings are consistent with the phase diagram of the polymer, which will facilitate the application of this strategy to other proteins and with other therapeutic models.


Histone demethylase KDM5A regulates the ZMYND8-NuRD chromatin remodeler to promote DNA repair.
Upon DNA damage, histone modifications are dynamically reshaped to accommodate DNA damage signaling and repair within chromatin. In this study, we report the identification of the histone demethylase KDM5A as a key regulator of the bromodomain protein ZMYND8 and NuRD (nucleosome remodeling and histone deacetylation) complex in the DNA damage response. We observe KDM5A-dependent H3K4me3 demethylation within chromatin near DNA double-strand break (DSB) sites. Mechanistically, demethylation of H3K4me3 is required for ZMYND8-NuRD binding to chromatin and recruitment to DNA damage. Functionally, KDM5A deficiency results in impaired transcriptional silencing and repair of DSBs by homologous recombination. Thus, this study identifies a crucial function for KDM5A in demethylating H3K4 to allow ZMYND8-NuRD to operate within damaged chromatin to repair DSBs.


Management of breast abscesses in nonlactating women.
Breast abscess in nonlactating women is a rare clinic-pathological entity. A retrospective analysis of all cases of breast abscesses in nonlactating women in a community teaching hospital from 2000 to 2006 was performed. We analyzed their clinical characteristics, prevalence of diabetes mellitus (DM), surgical and medical management, and clinical outcome. We identified 116 breast abscesses in 98 nonlactating women; 89 per cent of patients were black. At presentation, 63 patients (64%) had a known history of DM and eight patients (8%) had newly diagnosed DM. Patients with DM had an increased length of hospital stay than nondiabetic women (P < 0.01). Most patients (70%) were treated with incision and drainage and antibiotics with a mean time of abscess resolution of 47 +/- 54 days. There was no correlation with breast abscess and smoking history. Glycemic control was suboptimal with 46 per cent of subjects receiving insulin therapy during the hospital stay. We found a high prevalence of DM (72%) in nonlactating women presenting with breast abscess. Diabetic women had a longer hospital stay and longer duration of the abscess compared with the patients without diabetes. Diabetes screening in nonlactating women with breast abscess and intensified glycemic control might improve clinical outcome.


How accurately do novice surgeons place thoracic pedicle screws with the free hand technique?
Cadaver study. To evaluate with direct observation the errors made when novice resident surgeons place thoracic pedicle screws. To determine how many specimens need to be instrumented to assure an improvement in accuracy to currently published levels. Thoracic pedicle screw instrumentation has been shown to provide numerous benefits in spinal deformity surgery including 3 column fixation of the spinal elements, decreased need for thoracoplasty or anterior thoracic release and decreased operative time and blood loss. Three orthopaedic residents inexperienced in pedicle screw placement received an introductory teaching session. Intact thoracic vertebral body specimens were harvested from 15 cadaver spines. Each vertebral body was mounted on a clear Plexiglas frame with only the posterior surface anatomy visible to the surgeon. Each resident surgeon instrumented 5 thoracic spines verbalizing all perceived pedicle wall violations as they occurred. An observer recorded the accuracy of the gearshift probe, flexible probe, tap, and screw placement. Critically perforated screws were defined as a greater than 2 mm breach of the pedicle wall. Two hundred ninety-seven pedicles in 149 intact vertebral body specimens were instrumented. Eighty-five (29%) screws were not fully within the pedicle. Sixty-three (74%) were noncritical violations and 22 (26%) were critical violations. There were 18 (21%) screw violations not perceived by the surgeon to be outside the pedicle. There was a decrease in the proportion of total screw violations by the third cadaver (P < 0.001) and in critical screw violations by the fourth cadaver (P = 0.01). Novice resident surgeons placing thoracic pedicle screws in cadavers were able to significantly improve by the fourth cadaver to accuracy levels documented in the literature. Surgeons in training shouldpractice these skills in the laboratory before proceeding to the operating room.


Methane Dynamics in a Tropical Serpentinizing Environment: The Santa Elena Ophiolite, Costa Rica.
Uplifted ultramafic rocks represent an important vector for the transfer of carbon and reducing power from the deep subsurface into the biosphere and potentially support microbial life through serpentinization. This process has a strong influence upon the production of hydrogen and methane, which can be subsequently consumed by microbial communities. The Santa Elena Ophiolite (SEO) on the northwestern Pacific coast of Costa Rica comprises ~250 km2 of ultramafic rocks and mafic associations. The climatic conditions, consisting of strongly contrasting wet and dry seasons, make the SEO a unique hydrogeological setting, where water-rock reactions are enhanced by large storm events (up to 200 mm in a single storm). Previous work on hyperalkaline spring fluids collected within the SEO has identified the presence of microorganisms potentially involved in hydrogen, methane, and methanol oxidation (such as Hydrogenophaga, Methylobacterium, and Methylibium spp., respectively), as well as the presence of methanogenic Archaea (such as Methanobacterium). Similar organisms have also been documented at other serpentinizing sites, however their functions have not been confirmed. SEO's hyperalkaline springs have elevated methane concentrations, ranging from 145 to 900 μM, in comparison to the background concentrations (<0.3 μM). The presence and potential activity of microorganisms involved in methane cycling in serpentinization-influenced fluids from different sites within the SEO were investigated using molecular, geochemical, and modeling approaches. These results were combined to elucidate the bioenergetically favorable methane production and/or oxidation reactions in this tropical serpentinizing environment. The hyperalkaline springs at SEO contain a greater proportion of Archaea and methanogens than has been detected in any terrestrial serpentinizing system. Archaea involved in methanogenesis and anaerobic methane oxidation accounted from 40 to 90% of total archaeal sequences. Genes involved in methanogenic metabolisms were detected from the metagenome of one of the alkaline springs. Methanogenic activities are likely to be facilitated by the movement of nutrients, including dissolved inorganic carbon (DIC), from surface water and their infiltration into serpentinizing groundwater. These data provide new insight into methane cycle in tropical serpentinizing environments.


Effects of circulating antigen on monoclonal antibody localization.
The potential effects of free circulating antigen on the ability of monoclonal antibodies to target tumors in vivo were investigated. Tumor models consisted of HCC, NuE and PLC cell lines producing AFP xenografted in nude mice, and the NuE-treated mouse designated as the NuE-bearing mouse injected with AFP prior to the administration of antibody. Immunoscintigraphy and biodistribution were evaluated by using 125I-labeled monoclonal antibody 19F12 raised against AFP. Gel chromatography analysis of plasma from the PLC-bearing mouse which excreted 400 ng AFP/ml in blood injected with 125I-19F12 indicated that all injected antibody 19F12 formed an immune complex in plasma. No immune complex was present in plasma from the NuE-bearing mice, where blood AFP levels were 7 ng/ml, while the intact antibody was found to remain partly in plasma from the NuE-treated mouse. Radioactivities in the whole body of NuE-bearing and NuE-treated mice eventually cleared at the same rate. Our experimental results indicated that the endogeneous circulating antigen retained the antibody in the whole body for a longer period. The ability of monoclonal antibodies to target tumors was influenced not only by how much antigen was present but also by how rapid the antigen was cleared in the blood.


Spontaneous shrinkage of vestibular schwannoma.
"Watch, wait, and rescan" (WWR) has an established place as a successful management option for a significant proportion of vestibular schwannomas (VS) as an alternative to microsurgical removal or stereotactic radiotherapy. VS may grow slowly and continuously, followed by stagnation or even shrinkage. We present two case reports of spontaneous shrinkage of VS along with a review of the literature. A 29-year-old female presented with a progressive history of visual blurring and intermittent diplopia over 2 months. A 29 mm of maximum intracranial diameter (ICD) VS with secondary obstructive hydrocephalus was diagnosed. The patient underwent a ventriculo-peritoneal shunt with resolution of her symptoms and opted for initial WWR management. Interval scanning between 2007 and 2014 showed progressive reduction in the maximum ICD together with reduction in the degree of central tumor enhancement. Maximum ICD at most recent follow up was 22 mm. A 28-year-old female was referred with right sensorineural deafness. A right VS of maximum ICD of 27 mm was diagnosed. Initial WWR management was planned after discussion. Serial imaging showed an initial increase in the size of the tumor followed by progressive reduction in size. The most recent follow up showed a maximum ICD of 20 mm. Early WWR management can be associated with spontaneous shrinkage of VS over time. Prospective clinical study of larger numbers of such cases using the UK VS database may help to identify predictive factors for the spontaneous regression of VS.


Integration of clinical judgment in the nursing curriculum: challenges and perspectives.
The purpose of this qualitative, multiple-case study design was to better understand the influence of the nursing curriculum on clinical judgment development in baccalaureate nursing students and the capacity to provide safe nursing practice in health care settings. A sample of 20 preceptors for new graduate nurses were selected from three hospitals in Lebanon, and curriculum documents of three nursing programs provided data to determine the influence of curriculum on clinical judgment development. The preceptors' responses and curriculum data were triangulated, resulting in identification of strengths and weaknesses in the development of the clinical judgment ability of nursing students. The findings provide specific information regarding the influence of the nursing curriculum on the development of clinical judgment abilities, as well as implications for integration of new graduates into professional nursing practice. Strategies are described that can be used globally as baccalaureate nursing programs embrace and strengthen the partnership with service.


Inhibition of HT-29 human colon cancer growth under the renal capsule of severe combined immunodeficient mice by an analogue of 1,25-dihydroxyvitamin D3, DD-003.
An analogue of 1,25-dihydroxyvitamin D3, 22(S)-24-homo-26,26,26,27,27,27-hexafluoro-1 alpha,22,25-trihydroxyvitamin D3 (DD-003), showed 10-fold greater inhibiting effect than 1,25-dihydroxyvitamin D3 on the growth of HT-29 human colonic adenocarcinoma cells in culture. To examine the anticancer activity of DD-003 in vivo, a fibrin clot of HT-29 cells was prepared with fibrinogen and thrombin and implanted under the renal capsule of the severe combined immunodeficient mouse. Starting 7 days after implantation of HT-29 tumor, mice were given 3 micrograms/kg body weight of DD-003 or the vehicle i.p. every other day for 5 times. The HT-29 tumor grew rapidly in control mice; malignant growth was clearly observed with mitosis, massive tumor angiogenesis, and invasion into normal kidney tissue. Tumors in DD-003 treated mice were smaller with less invasion compared to the control. Administration of DD-003 inhibited growth of HT-29 tumor by 63%. Serum calcium concentrations and body weights of the treated mice were similar to those of the control. DD-003 inhibited growth of HT-29 tumor in a dose-dependent manner over the range of 0.1-10 micrograms/kg body weight, with no increase of serum calcium concentration observed at any dose level. When DD-003 was withdrawn after 2 weeks of treatment, tumor growth resumed. Since chemosensitivity tested by the subrenal capsule assay correlates well with clinical response, DD-003 may be clinically applicable in procedures such as postsurgical chemotherapy of colon cancer.


Acinar epithelial cell laminin-receptors in labial salivary glands in Sjögren's syndrome.
To analyze the epithelial cell-basement membrane attachment, in particular in the secretory end pieces (responsible for secretion of saliva) and in Sjögren's syndrome (SS) characterized by acinar cell failure. Immunohistochemistry with laminin receptor chain-specific monoclonal antibodies to integrin (Int) subunits, Lutheran blood group antigen and alpha-dystroglycan. Only acinar cells contained Int alpha1 and alpha2 subunits. This staining was interrupted but strong in controls, but very weak in SS. Both acinar and ductal cells contained Int alpha3, alpha6, b1 and b4 and Lutheran blood group antigen and ductal cells also contained alpha-dystroglycan. These staining patterns were similar in SS and controls. Binding of the acinar and ductal cells to the basement membrane laminins seems to be mediated by Int alpha3b1, alpha6b1 and alpha6b4 integrin-receptors and Lutheran blood group antigen and alpha-dystroglycan non-integrin receptors. This structure-supporting system is intact in SS, compatible with the maintenance of the tubuloalveolar architecture of the SS glands. The irregular staining pattern of the acinus-specific Int alpha1b1 and alpha2b1 was compatible with a regulated signaling role, which was apparently impaired in SS. Indeed, their laminin counterparts (Lm -1/111 and -2/211) are also aberrant in SS revealing this as the central cell-matrix defect in the syndrome.


Association of age, sex, cognitive dysfunction, and disability with major depressive symptoms in an elderly sample.
Previous studies have yielded conflicting results regarding the association of age, sex, and cognitive deficit with depression in the elderly. However, there is agreement about a relationship between depressive symptoms and disability. The authors previously conducted a factor analysis of the symptoms of major depression in elderly subjects and found that the symptoms clustered into factors of mood disturbance and motivation disturbance. The aim of the present study was to replicate these findings in a larger population sample and relate some of the variables possibly associated with depression to these two factors. A population sample of 1,304 persons aged 75 years or older registered in a parish of Stockholm were examined by physicians to determine DSM-III-R depressive symptoms and disability in activities of daily living. The Mini-Mental State examination was also performed. Factor analysis showed factors of mood and motivation symptoms, and these were related differently to the associated variables. When the other associated variables were controlled for, age was unrelated to both types of symptoms. Women had more mood disturbance, but men had slightly more motivation disturbance. As cognitive function declined, mood disturbance first increased, then decreased. Motivation symptoms increased sharply with decreasing cognitive function. A relationship was found between increasing disability and both the mood and motivation symptoms. In the elderly, symptoms of depression involve either mood or motivation disturbance and the two types of symptoms are associated with different variables.


Spectral Analysis of Chinese Medicinal Herbs Based on Delayed Luminescence.
Traditional Chinese medicine (TCM) plays a critical role in healthcare; however, it lacks scientific evidence to support the multidimensional therapeutic effects. These effects are based on experience, and, to date, there is no advanced tool to evaluate these experience based effects. In the current study, Chinese herbal materials classified with different cold and heat therapeutic properties, based on Chinese medicine principles, were investigated using spectral distribution, as well as the decay probability distribution based on delayed luminescence (DL). A detection system based on ultraweak biophoton emission was developed to determine the DL decay kinetics of the cold and heat properties of Chinese herbal materials. We constructed a mathematical model to fit the experimental data and characterize the properties of Chinese medicinal herbs with different parameters. The results demonstrated that this method has good reproducibility. Moreover, there is a significant difference (p < 0.05) in the spectral distribution and the decay probability distribution of Chinese herbal materials with cold and heat properties. This approach takes advantage of the comprehensive nature of DL compared with more reductionist approaches and is more consistent with TCM principles, in which the core comprises holistic views.


An efficient robust sound classification algorithm for hearing aids.
An efficient robust sound classification algorithm based on hidden Markov models is presented. The system would enable a hearing aid to automatically change its behavior for differing listening environments according to the user's preferences. This work attempts to distinguish between three listening environment categories: speech in traffic noise, speech in babble, and clean speech, regardless of the signal-to-noise ratio. The classifier uses only the modulation characteristics of the signal. The classifier ignores the absolute sound pressure level and the absolute spectrum shape, resulting in an algorithm that is robust against irrelevant acoustic variations. The measured classification hit rate was 96.7%-99.5% when the classifier was tested with sounds representing one of the three environment categories included in the classifier. False-alarm rates were 0.2%-1.7% in these tests. The algorithm is robust and efficient and consumes a small amount of instructions and memory. It is fully possible to implement the classifier in a DSP-based hearing instrument.


Evaluation of ELISA and RAST using purified antigens for diagnosis of hydatidosis.
Purified Echinococcus granulosus antigens have been used in ELISA and RAST to improve the serodiagnosis of hydatidosis. Results in ELISA confirm the interest of purified antigens for a specific diagnosis and the particular relevance of antigen 5. Antigen B has been shown to be relevant in RAST since the highest correlation was obtained between total IgE and antigen B-specific IgE. Moreover, no false positive were shown as using RAST with antigen B. Such a study has now to be extended at a large scale to appreciate the evolutivity of the disease.


Liver membrane composition after short-term parenteral nutrition with and without taurine in guinea pigs: the effect to taurine.
Having recently demonstrated that taurine supplementation prevents total parenteral nutrition (TPN)-induced cholestasis, we chose to use this model to examine plasma membrane composition in relation to bile formation. Male guinea pigs received daily a mixture of glucose and of the amino acid solution Travasol with or without added taurine (1.2 mM). After 3 days, bile was collected and liver plasma membrane fractions enriched in sinusoidal lateral membrane and bile canalicular membrane domains were isolated. In animals receiving TPN alone, bile flow and biliary secretory rate of bile acid and bicarbonate decreased significantly compared with controls. Although membrane ATPases (Na+K+ and Mg+) were unchanged, TPN induced an increase in the lipid to protein ratio and a decrease of polyunsaturated fatty acids, in conjunction with a higher content of diene conjugates in sinusoidal lateral membrane fractions. Taurine corrected these changes and, in addition, reduced significantly the cholesterol to phospholipid ratio in both membrane fractions. The data show that changes in liver cell membranes occur in TPN-induced cholestasis and suggest that free radical injury may play a role. As taurine prevented cholestasis as well as membrane changes, it is suggested that taurine should be added to amino acid solutions used for parenteral nutrition.


Effect of UV-B erythema of psoralen, trimethylpsoralen, and 8 methoxypsoralen.
The MED for UV-B was measured 2 h and 24 h after oral intake of Psoralen (P) 0.49 mg/kg in 10 healthy volunteers. MED was increased when UV exposure had taken place 2 h after intake. The same increase was observed after 0.24 mg/kg and 0.98 mg/kg, with a non-significant dose dependence. This effect was not detectable when UV exposure had taken place 24 h after oral intake of the drug. In a second experiment the effects of oral intake of both trimethylpsoralen (TMP) and 8 Methoxypsoralen (8 MOP) mg/kg, were assessed in 29 subjects. While TMP increased MED when taken 2 h before UV exposure (p less than 0.001), 8 MOP had the opposite effect (p less than 0.01). TMP effect was observed mainly in fair-haired people (p less than 0.05) and 8 MOP effect mainly in females (p less than 0.05).


Role of endothelin in chronic renal failure--developments in renal involvement.
Endothelin (ET)-1 is a potent vasoconstrictor with profibrotic and proinflammatory effects. Increasing evidence suggests that ET-1 and its cognate receptors are involved in a variety of progressive renal disorders, including diabetes, hypertension and glomerulonephritis. Several laboratory studies have demonstrated elevated expression of ET-1, which colocalizes with glomerular and tubulointerstitial injury, in addition to enhanced urinary excretion. Moreover, ET-1 expression correlates with disease severity and renal function. With the availability of ET receptor antagonists, a pathogenetic role has been further corroborated in animal models, demonstrating both structural and functional improvement. Thus, antagonizing the ET system may be useful in major renal pathologies associated with glomerular and tubulointerstitial damage.


The time course and microbiology of surgical site infections after head and neck free flap surgery.
Determine the time of onset and microbiology of surgical site infections (SSIs) following head and neck free flap reconstructive surgeries. Retrospective cohort study. All 504 free flap surgical cases (484 patients) performed April 1, 2009 to September 30, 2013 were reviewed; SSIs occurring ≤30 days postoperatively were evaluated. Admission screening for methicillin-resistant Staphylococcus aureus (MRSA) colonization was performed on all patients. Flap-recipient site infections (flap SSIs) occurred in 67 cases (13.3%), one-third week 1 postoperatively, one-third week 2, one-third days 15 to 30; 45% occurred after hospital discharge. Wound cultures were polymicrobial, but 25% grew only normal oral flora, whereas 75% grew pathogens not part of normal oral flora, such as gram-negative bacilli (44% of cases), MRSA (20%), and methicillin-sensitive S aureus (MSSA) (16%). The frequency of these pathogens did not vary significantly by the time of SSI onset. In 67%, cultures included at least one pathogen resistant to the prophylactic antibiotic used. Clindamycin prophylaxis was a significant risk factor for flap SSI and for early partial or complete flap loss from infection. Donor SSIs occurred in 22 cases (4.4%), 95% >1 week postoperatively, and MRSA or MSSA were the primary pathogens in 89%. Of the 25 patients colonized with MRSA on admission, 40% developed a flap or donor SSI, a rate significantly higher than in non-colonized patients. Gram-negative bacilli, MRSA, and MSSA were significant SSI pathogens, and late onset of infection was common. Better screening, decolonization, and prophylaxis may reduce SSI rates. 2b


Erythroid progenitors in mouse bone marrow detected by macroscopic colony formation in culture.
Methods for the cultivation of erythroid colonies in vitro are expected to allow selective assay of the earliest committed erythropoietic progenitors in the hemopoietic tissues of man and other species. In the present study, factors affecting erythroid colony formation were examined in methyl cellulose cultures of mouse bone marrow. Efficiency of colony formation observed after 2 days of culture was increased as much as 5-fold (to an average of 325 colonies/10-5 nucleated marrow cells) by the addition of thiol (either beta-mercaptoethanol or alphal-thioglycerol) at a final concentration of 10 minus 4 M. Optimum efficiency required 0.5 erythropoietin units/ml and was influenced by the purity of the preparation. When cultures contained thiol and high doses (3 units/ml) of purified erythropoietin, a second population of erythroid colonies became apparent after 5 days of culture, and increased in size to macroscopic dimensions by the tenth day, when they contained as many as 10-4 cells. Feeding was not required. These colonies, thought to be analogous to the "bursts" reported by Axelrad and coworkers in plasma clot cultures, were observed here at a 6-fold higher frequency (25/10-5 marrow cells) and were linearly related to the number of marrow cells plated, down to limiting numbers of colonies. On the basis of their impressive proliferative potential exhibited in culture, the cells originating these colonies are thought to represent a class of very early erythropoietin-responsive red cell progenitors.


Pediatric optic neuritis.
Pediatric optic neuritis may be challenging to diagnose and treat. Significant clinical investigation of optic neuritis occurring in adults guides current clinical practices. Differences in presentation and prognosis exist for pediatric patients with optic neuritis when compared with adults including the risk of developing multiple sclerosis. The aim of this review is to provide an update on latest advances in the diagnosis, treatment and current research concerning pediatric optic neuritis. Limited case series and retrospective reviews constitute much of the data we know about patients with pediatric optic neuritis. Pediatric optic neuritis is included in the spectrum of neuroinflammatory diseases. Testing modalities (ocular coherence tomography and visual evoked potentials) and serologic testing (antibodies against aquaporin-4 and myelin oligodendrocyte glycoprotein) are being investigated for diagnostic and prognostic value. The low incidence of pediatric optic neuritis results in small sample sizes may contribute to conflicting results of different studies. Recent advances in diagnostic and serologic testing in pediatric neuritis may offer better diagnosis, treatment and prediction of prognosis. Validation requires well designed prospective research.


Bullfrog dorsal root ganglion cells having tetrodotoxin-resistant spikes are endowed with nicotinic receptors.
1. Intracellular recordings were made from bullfrog dorsal root ganglion (DRG) neurons in vitro. They were divided into three types, As, Ar, and C, according to their conduction velocity and their sensitivity to tetrodotoxin [TTX (less than or equal to 1 microM)]; an As neuron had a fast conduction velocity (13-50 m/s, mean = 31 m/s, n = 73) and TTX-sensitive sodium soma spikes: an Ar neuron showed a fast conduction velocity (4-28 m/s, mean = 14 m/s, n = 52) and TTX-resistant sodium soma spikes; and a C neuron had a slow conduction velocity (0.16-0.8 m/s, mean = 0.4 m/s, n = 49) and TTX-resistant sodium-calcium soma spikes. 2. Superfusion of acetylcholine [ACh (0.3 microM-1 mM)] produced a fast depolarization in 70% of Ar and in 50% of C neurons. No As neuron showed a fast depolarization in response to ACh. The ACh-induced fast response persisted in calcium-free or TTX-containing solutions. 3. The response in both Ar and C neurons was similar except in time course; the response was always more rapid in C than in Ar neurons. The response was always associated with a decreased membrane resistance and reversed in polarity at about -30 mV. The reversal potential varied with both sodium and potassium concentrations of the superfusing solutions. 4. Nicotine, (+)-tubocurarine [(+)-TC], and hexamethonium reversibly blocked the ACh fast response.(ABSTRACT TRUNCATED AT 250 WORDS)


Father-child and mother-child interaction in families with a child feeding disorder: The role of paternal involvement.
To date, research about feeding disorder (FD) has focused almost exclusively on the mother-child dyad, ignoring fathers' roles. The current study investigated father-child interactions with children having FD. The sample consisted of 67 children (1-3 years old) and their mothers and fathers. Thirty-four children, diagnosed with a nonorganic-based FD (FD group) and 33 children without an FD (control group) were matched for age, gender, birth order, and maternal education. Data were collected during home visits. Mothers were interviewed about their and the father's involvement in childcare. In addition, mother-child and father-child interactions were videotaped during play and feeding. Both mothers and fathers from the FD group experienced less positive parent-child interactions than did parents in the control group. Furthermore, mothers in the FD group reported greater maternal versus paternal childcare involvement than did control group mothers. Finally, FD group mothers exhibited more parental sensitivity than did fathers during feeing interactions; however, this difference was observed only when coupled with low paternal involvement. In families where fathers were highly involved, no difference was evident in paternal and maternal sensitivity. These findings highlight the importance of fathers' involvement, especially in families with children exhibiting an FD.


Radiation induced sarcoma of oral cavity-a rare case report and a short review.
Radiation - Induced Sarcomas(RIS) are rare clinical entity. They arise from the previously irradiated areas with a prolonged latency period. In this case report we present a rare case of radiation induced sarcoma with a brief review of literature. We report radiation-induced sarcoma in a 67-year-old male, involving the left Retromolar Trigone region following treatment of squamous cell carcinoma of tongue with wide excision, neck dissection and post-operative radiation. Diagnosis of radiation induced sarcoma was confirmed by history, latency period and biopsy.


The Effect of Q-Switched Nd:YAG 1064 nm/532 nm Laser in the Treatment of Onychomycosis In Vivo.
In this prospective clinical study, the Q-Switched Nd:YAG 1064 nm/532 nm laser (Light Age, Inc., Somerset, NJ, USA) was used on 131 onychomycosis subjects (94 females, 37 males; ages 18 to 68 years). Mycotic cultures were taken and fungus types were detected. The laser protocol included two sessions with a one-month interval. Treatment duration was approximately 15 minutes per session and patients were observed over a 3-month time period. Laser fluencies of 14 J/cm(2) were applied at 9 billionths of a second pulse duration and at 5 Hz frequency. Follow-up was performed at 3 months with mycological cultures. Before and after digital photographs were taken. Adverse effects were recorded and all participants completed "self-evaluation questionnaires" rating their level of satisfaction. All subjects were well satisfied with the treatments, there were no noticeable side effects, and no significant differences were found treating men versus women. At the 3-month follow-up 95.42% of the patients were laboratory mycologically cured of fungal infection. This clinical study demonstrates that fungal nail infections can be effectively and safely treated with Q-Switched Nd:YAG 1064 nm/532 nm laser. It can also be combined with systemic oral antifungals providing more limited treatment time.


Clinical Biomarkers and Prediction Models for Poststroke Epilepsy: Have We Settled the Scores Yet?
In an era of time-dependent reperfusion and recanalization therapy for stroke leading to improved survival, there is a growing population at risk of poststroke epilepsy (PSE). Accumulating evidence suggests a multidirectional interaction among stroke, PSE, and dementia in stroke survivors. There is no evidence to justify prophylactic antiseizure medication (ASM) to reduce these morbidities. Although several predictive molecular biomarkers and scoring models have been proposed, they remain inadequately validated for stratifying risk and indicating who will benefit from prophylactic ASM. Studies leveraging advances in genetics, metabolomics, electrophysiology, imaging, and artificial intelligence (AI) may help to discover noninvasive molecular biomarkers and easy-to-score models. These discoveries should improve our understanding of epileptogenesis in PSE and identify new pharmacologic targets. Besides, accurately identifying high-risk patients and timely initiating prophylactic ASM therapy has the potential to disrupt the feed-forward multidirectional interaction among stroke, PSE, and dementia.


Aging and Autism Spectrum Disorder: A Naturalistic, Longitudinal Study of the Comorbidities and Behavioral and Neuropsychiatric Symptoms in Adults with ASD.
Little is known about Autism Spectrum Disorder (ASD) in persons over age 50. In a retrospective, naturalistic review of 74 individuals aged 30 and older meeting DSM-5 criteria for ASD, the point prevalence of behavioral and neuropsychiatric symptoms (BNPS) declined significantly for 12 of 13 BNPS over a mean of 25 years while many other features of ASD remained stable. GI disorders (68.9%) and seizure disorders (23%) were common, and 25.7% of the sample had a BMI >30. Females were more likely to engage in screaming (p < 0.05) and oppositional behavior (p < 0.05). Current age did not have a significant effect on BNPS prevalence.


Bone marrow as a source of endothelial cells and NeuN-expressing cells After stroke.
After an ischemic event, bone marrow-derived cells may be involved in reparative processes. There is increasing evidence that bone marrow-derived stem cells may be a source of endothelial cells and organ-specific cells. Our objectives were to determine whether bone marrow-derived cells were a source of endothelial cells and neurons after cerebral ischemia. We transplanted bone marrow from male C57 BL/6-TgN (ACTbEGFP)1Osb mice, which express green fluorescent protein (GFP), into female C57 BL/6J mice. The recipient mice then underwent suture occlusion of the middle cerebral artery (MCA), and bone marrow- derived cells were tracked by GFP epifluorescence and Y chromosome probe. Within 3 days and at 7 and 14 days after MCA occlusion, bone marrow-derived cells incorporated into the vasculature in the ischemic zone and expressed an endothelial cell phenotype. Few bone marrow-derived cells incorporated into the vasculature 24 hours after MCA occlusion. Some bone marrow-derived cells also expressed the neuronal marker NeuN at 7 and 14 days after ischemia. Postnatal vasculogenesis occurs in the brain in the setting of a cerebral infarction. Bone marrow-derived cells are a source of endothelial cells and NeuN-expressing cells after cerebral infarction. This plasticity may be exploited in the future to enhance recovery after stroke.


Coronary artery disease burden relation with the presentation of acute cardiac events and ventricular fibrillation.
Evaluate the differences in coronary artery disease (CAD) burden between patients with ischemic resuscitated, ischemic refractory VT/VF OHCA events and N/STEMI. Refractory out-of-hospital cardiac arrest patients presenting with initial shockable rhythms (VT/VF OHCA) have the highest mortality among patients with acute cardiac events. No predictors of VT/VF OHCA refractoriness have been identified. A retrospective cohort design was used to assess baseline characteristics, clinical outcomes, and the angiographic severity of disease among patients with VT/VF OHCA undergoing emergent coronary angiography at the University of Minnesota Medical Center. The Gensini score was calculated for all patients to assess the angiographic burden of CAD. For patients with ischemia-related cardiac arrest, outcomes were further compared to an independent non-OHCA population presenting with N/STEMI. During the study period, 538 patients were admitted after VT/VF OHCA. Among them, 305 presented with resuscitated, and 233 with refractory VT/VF. 66% of resuscitated and 70% of refractory VT/VF had an underlying, angiographically documented, ischemic etiology. Ischemic resuscitated and refractory VT/VF had significant differences in Gensini score, (80.7 ± 3.6 and 127.6 ± 7.1, respectively, p < 0.001) and survival (77.3% and 30.0%, respectively, p < 0.001). Both groups had a higher CAD burden and worse survival than the non-OHCA N/STEMI population (360 patients). Ischemic refractory VT/VF was significantly more likely to present with chronic total occlusion in comparison to both N/STEMI and ischemic resuscitated VT/VF. Ischemia-related, refractory VT/VF OHCA has a higher burden of CAD and the presence of CTOs compared to resuscitated VT/VF OHCA and N/STEMI.


Fluoride-releasing restorative materials and secondary caries.
Secondary caries are responsible for 60% of all replacement restorations in the typical dental practice. Risk factors for secondary caries are similar to those for primary caries development. Unfortunately, it is not possible to predict accurately which patients are at risk for restoration failure. Fluoride-releasing dental materials provide for improved resistance against primary and secondary caries in coronal and root surfaces and have become a part of the dentist's armamentarium. This article discusses the improvement in the properties of dental materials with the ability to release fluoride. It is anticipated that in the near future, the vast majority of restorative procedures will employ fluoride-releasing dental materials as bonding agents, cavity liners, luting agents, adhesives for orthodontic brackets, and as definitive restoratives.


Multimodality Imaging Evaluation to Detect Subtle Right Ventricular Involvement in Patients with Acute Myocarditis and Preserved Left Ventricular Ejection Fraction.
Background: Evaluation of the right ventricle (RV) in patients with acute myocarditis (MY) remains challenging with both 2D transthoracic echocardiography (TTE) and cardiovascular magnetic resonance (CMR). We examined the incremental diagnostic value of CMR feature tracking (FT) to evaluate RV involvement in patients with myocarditis. Methods: We enrolled 54 patients with myocarditis and preserved left ventricle (LV) ejection fraction (EF). The CMR protocol included T2-weighted images for edema detection and late gadolinium enhancement (LGE) images. Global longitudinal strain (GLS) of the left ventricle (LV) and RV free wall strain (CMR-FWS) were obtained with CMR-FT. We identified 34 patients (62%) with inferior and lateral segment (IL-MY) involvement and 20 (38%) noIL-MY in case of any other myocardial segment involved. Here, 20 individuals who underwent CMR for suspected cardiac disease, which was not confirmed thereafter, were considered as the control population. Results: TTE and CMR showed normal RV function in all patients without visible RV involvement at the LGE or T2-weighted sequences. At CMR, LV-GLS values were significantly lower in patients with MY compared to the control group (median -19.0% vs. -21.0%, p = 0.029). Overall, CMR RV-FWS was no different between MY patients and controls (median -21.2% vs. -23.2 %, p = 0.201) while a significant difference was found between RV FWS in IL-MY and noIL-MY (median -18.17% vs. -24.2%, p = 0.004). Conclusions: CMR-FT has the potential to unravel subclinical RV involvement in patients with acute myocarditis, specifically in those with inferior and lateral injuries that exhibit lower RV-FWS values. In this setting, RV deformation analysis at CMR may be effectively implemented for a comprehensive functional assessment.


Stochastic thermodynamics in the strong coupling regime: An unambiguous approach based on coarse graining.
We consider a classical and possibly driven composite system X⊗Y weakly coupled to a Markovian thermal reservoir R so that an unambiguous stochastic thermodynamics ensues for X⊗Y. This setup can be equivalently seen as a system X strongly coupled to a non-Markovian reservoir Y⊗R. We demonstrate that only in the limit where the dynamics of Y is much faster than X, our unambiguous expressions for thermodynamic quantities, such as heat, entropy, or internal energy, are equivalent to the strong coupling expressions recently obtained in the literature using the Hamiltonian of mean force. By doing so, we also significantly extend these results by formulating them at the level of instantaneous rates and by allowing for time-dependent couplings between X and its environment. Away from the limit where Y evolves much faster than X, previous approaches fail to reproduce the correct results from the original unambiguous formulation, as we illustrate numerically for an underdamped Brownian particle coupled strongly to a non-Markovian reservoir.


Population-Level Differentiation in Growth Rates and Leaf Traits in Seedlings of the Neotropical Live Oak Quercus oleoides Grown under Natural and Manipulated Precipitation Regimes.
Widely distributed species are normally subjected to spatial heterogeneity in environmental conditions. In sessile organisms like plants, adaptive evolution and phenotypic plasticity of key functional traits are the main mechanisms through which species can respond to environmental heterogeneity and climate change. While extended research has been carried out in temperate species in this regard, there is still limited knowledge as to how species from seasonally-dry tropical climates respond to spatial and temporal variation in environmental conditions. In fact, studies of intraspecific genetically-based differences in functional traits are still largely unknown and studies in these ecosystems have largely focused on in situ comparisons where environmental and genetic effects cannot be differentiated. In this study, we tested for ecotypic differentiation and phenotypic plasticity in leaf economics spectrum (LES) traits, water use efficiency and growth rates under natural and manipulated precipitation regimes in a common garden experiment where seedlings of eight populations of the neotropical live oak Quercus oleoides were established. We also examined the extent to which intraspecific trait variation was associated with plant performance under different water availability. Similar to interspecific patterns among seasonally-dry tropical tree species, live oak populations with long and severe dry seasons had higher leaf nitrogen content and growth rates than mesic populations, which is consistent with a "fast" resource-acquisition strategy aimed to maximize carbon uptake during the wet season. Specific leaf area (SLA) was the best predictor of plant performance, but contrary to expectations, it was negatively associated with relative and absolute growth rates. This observation was partially explained by the negative association between SLA and area-based photosynthetic rates, which is contrary to LES expectations but similar to other recent intraspecific studies on evergreen oaks. Overall, our study shows strong intraspecific differences in functional traits in a tropical oak, Quercus oleoides, and suggests that precipitation regime has played an important role in driving adaptive divergence in this widespread species.


Inflammatory bowel diseases: a dysfunction of brain-gut interactions?
The gut has the capacity to function as an autonomous organ. However, in normal conditions, the gut and the central nervous system talk to each other through the autonomic nervous system (ANS), represented by the sympathetic (i.e. the splanchnic nerves) and the parasympathetic nervous system (i.e. the vagus nerve and the sacral parasympathetic pelvic nerves). The brain is able to integrate inputs coming from the digestive tract inside a central autonomic network organized around the hypothalamus, limbic system and cerebral cortex and in return to modify the ANS and the hypothalamic pituitary adrenal axis (HPA axis). An abnormal functioning of these brain-gut interactions has been described in irritable bowel syndrome (IBS) classically considered as a biopsychosocial model where stress plays a promoting role. Inflammatory bowel diseases (IBD) result from an inappropriate inflammatory response to intestinal microbes in a genetically susceptible host. In this article we review the current knowledge on the possible involvement of a dysfunction of brain-gut interactions in the pathogeny of IBD as represented by a dysfunction of the ANS, an abnormal HPA axis and cholinergic anti-inflammatory pathway, a deleterious effect of stress and depression as well as an abnormal coupling of the prefrontal cortex-amygdala complex and an abnormal relation between the microbiota and the brain as pro-inflammatory factors. Therapeutic approaches with the aim to restore an equilibrium of these brain-gut interactions are of interest.


Two cases of fatal encephalopathy related to Ifosfamide: an adverse role of aprepitant?
Ifosfamide is used in the treatment of sarcomas and other tumors. It sometimes provokes encephalopathy, which is a serious complication even if it is usually reversible within 48-72 h after drug cessation. Ifosfamide is required to be activated by hepatic cytochrome P450 (CYP), especially the 3A4 subtype, leading to 4-hydroxy-ifosfamide. Ifosfamide is also converted by CYP3A4 to inactive but neurotoxic metabolites. Aprepitant is a neurokinin-1 receptor antagonist that is a potent antiemetic used in combination with 5-HT3 antagonists and corticosteroids. Aprepitant has an inhibitory effect, as well as a possible inductive effect, on CYP3A4. Since ifosfamide and aprepitant are both substrates of CYP3A4, a pharmacokinetic interaction could result in secondary effects such as the potentialization of neurological side effects. In this report, we describe 2 cases of fatal encephalopathy in patients who have received both ifosfamide and aprepitant, and we discuss the mechanisms that could be involved. Our observations draw attention to the fact that aprepitant must be avoided, or at least used with caution, in patients who are receiving ifosfamide due to the risk of severe neurological side effects.


Students' views of training in Poland.
Psychological aspects of care figure high in the current nursing education curriculum, but how effectively are the teaching methods related to them? This small survey of students in a Polish university sought an answer, and revealed that the students felt they required more tuition on how interpersonal skills taught on the course can be directly applied to nursing practice.


The 13 angstroms structure of a chaperonin GroEL-protein substrate complex by cryo-electron microscopy.
The 13 angstroms resolution structures of GroEL bound to a single monomer of the protein substrate glutamine synthetase (GS(m)), as well as that of unliganded GroEL have been determined from a heterogeneous image population using cryo-electron microscopy (cryo-EM) coupled with single-particle image classification and reconstruction techniques. We combined structural data from cryo-EM maps and dynamic modeling, taking advantage of the known X-ray crystallographic structure and normal mode flexible fitting (NMFF) analysis, to describe the changes that occur in GroEL structure induced by GS(m) binding. The NMFF analysis reveals that the molecular movements induced by GS(m) binding propagate throughout the GroEL structure. The modeled molecular motions show that some domains undergo en bloc movements, while others show more complex independent internal movements. Interestingly, the substrate-bound apical domains of both the cis (GS(m)-bound ring) and trans (the opposite substrate-free ring) show counterclockwise rotations, in the same direction (though not as dramatic) as those documented for the ATP-GroEL-induced structure changes. The structural changes from the allosteric substrate protein-induced negative cooperativity between the GroEL rings involves upward concerted movements of both cis and trans equatorial domains toward the GS(m)-bound ring, while the inter-ring distances between the heptamer contact residues are maintained. Furthermore, the NMFF analysis identifies the secondary structural elements that are involved in the observed approximately 5 angstroms reduction in the diameter of the cavity opening in the unbound trans ring. Understanding the molecular basis of these substrate protein-induced structural changes across the heptamer rings provides insight into the origins of the allosteric negative cooperative effects that are transmitted over long distances (approximately 140 angstroms).


Proteomic analysis of the excretory-secretory proteins of the Trichinella spiralis L1 larva, a nematode parasite of skeletal muscle.
Trichinella spiralis is an intracellular nematode parasite of mammalian skeletal muscle. Infection of the muscle cell leads to the formation of a host-parasite complex that results in profound alterations to the host cell and a re-alignment of muscle-specific gene expression. The role of parasite excretory-secretory (ES) proteins in mediating these effects is currently unknown, largely due to the difficulty in identifying and assigning function to individual proteins. In this study, a global proteomics approach was used to analyse the ES proteins from T. spiralis muscle larvae. Following 2-DE of ES proteins,MALDI-TOF-MS and LC-MS/MS were used to identify the peptide spots. Specific Trichinella EST databases were assembled and used to analyse the data. Despite the current absence of a Trichinella genome-sequencing project, 43 out of 52 protein spots analysed were identified and included the major secreted glycoproteins. Other novel proteins were identified from matches with sequences in the T. spiralis database. Our results demonstrate the value of proteomics as a tool for the identification of Trichinella ES proteins and in the study of the molecular mechanism underpinning the formation of the host-parasite complex during Trichinella infections.


Enhancement of single particle rare earth doped NaYF4: Yb, Er emission with a gold shell.
Upconversion of infrared light to visible light has important implications for bioimaging. However, the small absorption cross-section of rare earth dopants has limited the efficiency of these anti-Stokes nanomaterials. We present enhanced excitation absorption and single particle fluorescent emission of sodium yttrium fluoride, NaYF4: Yb, Er based upconverting nanoparticles coated with a gold nanoshell through surface plasmon resonance. The single gold-shell coated nanoparticles show enhanced absorption in the near infrared, enhanced total emission intensity, and increased green relative to red emission. We also show differences in enhancement between single and aggregated gold shell nanoparticles. The surface plasmon resonance of the gold-shell coated nanoparticle is shown to be dependent on the shell thickness. In contrast to other reported results, our single particle experimental observations are corroborated by finite element calculations that show where the green/red emission enhancement occurs, and what portion of the enhancement is due to electromagnetic effects. We find that the excitation enhancement and green/red emission ratio enhancement occurs at the corners and edges of the doped emissive core.


Biweekly Raltitrexed Combined With Irinotecan as Second-Line Therapy for Patients With Metastatic Colorectal Cancer: A Phase II Trial.
Irinotecan-based doublet chemotherapy strategy was standard second-line backbone for patients with oxaliplatin-refractory metastatic colorectal cancer. The aim of this study was to evaluate tolerability and efficacy of raltitrexed combined with irinotecan biweekly administered as the second-line therapy for mCRC patients. The study was a prospective, single-center, non-randomized, open-label phase II clinical trial. Patients with mCRC after failure with oxaliplatin and fluoropyrimidine or its derivatives were enrolled. Irinotecan (180 mg/m2) and raltitrexed (2.5 mg/m2) were given intravenously on day 1. Cycles were repeated every 2 weeks. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included overall response rate (ORR), disease control rate (DCR), overall survival (OS), and adverse events (AEs). Between December 2012 and October 2016, 33 and 35 patients enrolled were assessed for response and safety, respectively. The ORR was 8.6%, and the DCR was 71.4%. The median PFS was 4.5 months (95% CI 3.8-5.2). The median OS was 12.0 months (95% CI 8.5-15.5). Four patients received conversion therapy to no evidence of disease (NED), and 2 patients were still alive with beyond 24 months survival. The most common grade 3/4 AEs were anorexia (14.3%), vomiting (14.3%), nausea (11.4%), fatigue (8.6%), and leukopenia (8.6%). No one died from treatment-related events. The incidence and severity of toxicity were irrelevant to UGT1A1 status. The combination of irinotecan with raltitrexed is an efficient, convenient, and acceptable toxic regimen for second-line treatment for mCRC patients.


Evaluation of tracheobronchial disease with helical CT with multiplanar and three-dimensional reconstruction: correlation with bronchoscopy.
The advantage of volumetric computed tomography in the thorax is the possibility of acquiring both multiplanar and three-dimensional (3D) images, thus enabling precise diagnosis and evaluation of extent of disease involving the airways. Multiplanar and 3D images appear to be useful for global understanding of the status of the tracheobronchial tree, particularly for evaluation of focal stenosis of the airways. Such images seem to be especially useful in evaluating the longitudinal extent of airway lesions, thus providing valuable information for preparing a road map for bronchoscopy, for surgical planning, and for follow-up of treatment response. However, multiplanar and 3D images do not appear to be useful in lesion detection or evaluation of transaxial extension. Multiplanar and 3D images also seem to be helpful in demonstrating whether a lesion is endobronchial, submucosal, or peribronchial. The quality of such images appears to be excellent or good in almost all patients.


Lack of ability of ciprofloxacin-rifampin prophylaxis to decrease infection-related morbidity in neutropenic patients given cytotoxic therapy and peripheral blood stem cell transplants.
We compared ciprofloxacin alone with ciprofloxacin plus rifampin (C + R) as a prophylactic antibacterial regimen for 40 patients with solid tumors treated with high-dose chemotherapy and autologous stem cell transplantation support. No differences were found between groups in the time elapsed to the onset of fever, incidence of febrile episodes, amphotericin B use, and length of hospital stay. However, C + R combination prophylaxis significantly reduced the incidence of gram-positive bacteremia (five versus zero episodes) but was associated with a higher incidence of drug-related side effects.


DNA-Polyelectrolyte Composite Responsive Microparticles for Versatile Chemotherapeutics Cleaning.
Drug therapy is among the most widely used methods in disease treatment. However, there remains a trade-off problem between drug dosage and toxicity. Blood purification by adsorption of excessive drugs during clinical treatment could be a solution for enhancing therapeutic efficacy while maintaining normal body function. Here, inspired by the intrinsic action mechanism of chemotherapeutic agents in targeting DNA in the cell nucleus, we present DNA-polyelectrolyte composite responsive microparticles for chemotherapeutics cleaning. The presence of DNA in the microparticles enabled the adsorption of multiple common chemotherapy drugs. Moreover, the microparticles are endowed with a porous structure and a photothermal-responsive ability, both of which contribute to improved adsorption by enhancing the contact of the microparticles with the drug solution. On the basis of that, the microparticles are integrated into a herringbone-structured microfluidic chip. The fluid mixing capacity and the enhanced drug cleaning efficiency of the microfluidic platform are validated on-chip. These results indicate the value of the DNA-polyelectrolyte composite responsive microparticles for drug capture and blood purification. We believe the microparticle-integrated microfluidic platform could provide a solution for settling the dosage-toxicity trade-off problems in chemotherapy.


Plasma-induced selectivity in bone cancer cells death.
Current therapies for bone cancers - either primary or metastatic - are difficult to implement and unfortunately not completely effective. An alternative therapy could be found in cold plasmas generated at atmospheric pressure which have already demonstrated selective anti-tumor action in a number of carcinomas and in more relatively rare brain tumors. However, its effects on bone cancer are still unknown. Herein, we employed an atmospheric pressure plasma jet (APPJ) to validate its selectivity towards osteosarcoma cell line vs. osteoblasts & human mesenchymal stem cells. Cytotoxicity following direct interaction of APPJ with cells is comparable to indirect interaction when only liquid medium is treated and subsequently added to the cells, especially on the long-term (72h of cell culture). Moreover, following contact of the APPJ treated medium with cells, delayed effects are observed which lead to 100% bone cancer cell death through apoptosis (decreased cell viability with incubation time in contact with APPJ treated medium from 24h to 72h), while healthy cells remain fully viable and unaffected by the treatment. The high efficiency of the indirect treatment indicates that an important role is played by the reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the gaseous plasma stage and then transmitted to the liquid phase, which overall lead to lethal and selective action towards osteosarcoma cells. These findings open new pathways for treatment of metastatic bone disease with a minimally invasive approach.


Measuring complexity in Brazilian economic crises.
Capital flows are responsible for a strong influence on the foreign exchange rates and stock prices macroeconomic parameters. In volatile economies, capital flows can change due to several types of social, political and economic events, provoking oscillations on these parameters, which are recognized as economic crises. This work aims to investigate how these two macroeconomic variables are related with crisis events by using the traditional complex measures due to Lopez-Mancini-Calbet (LMC) and to Shiner-Davison-Landsberg (SDL), that can be applied to any temporal series. Here, Ibovespa (Bovespa Stock Exchange main Index) and the "dollar-real" parity are the background for calculating the LMC and SDL complexity measures. By analyzing the temporal evolution of these measures, it is shown that they might be related to important events that occurred in the Brazilian economy.


The significance of high molecular weight kininogen for contact activation of rat blood coagulation, in vitro.
The involvement of the high molecular weight rat kininogen in the activation of the rat contact system by kaolin-cephalin, kaolin, sulfatides and ellagic acid has been investigated, using a rat plasma congenitally devoid of this kininogen. Coagulation times induced by these activators were shorter in normal as well as in deficient rat plasma than in normal human plasma. Coagulation times were prolonged in deficient rat plasma, when the incubation times was three min or less. By kaolin or cephalin-kaolin, this prolongation disappeared when the incubation time reached ten min. The activation of plasma prekallikrein developed slowly in deficient plasma with all the triggers but reached control level after ten min of incubation. By kaolin-cephalin, the activation of Hageman factor was weak and slow in deficient plasma during the ten min of incubation. In rat, high molecular weight kininogen plays thus a role in the activation of the contact system by these triggers. But this role seems to be less important than in human plasma.


A Common Medication with an Uncommon Adverse Event: A Case of Doxycycline-induced Pancreatitis.
Drug-induced pancreatitis is a rare entity. The diagnostic criteria for drug-induced pancreatitis include the development of pancreatitis during drug therapy, elimination of all other possible causes, resolution with discontinuation of the offending drug, and reappearance on using the same drug. Several drugs have been implicated in having an association with pancreatitis. Tetracyclines are considered to be a Class I medication (medications implicated in greater than 20 reported cases of acute pancreatitis). However, there are very few reported cases of doxycycline-induced acute pancreatitis. We report the case of a 55-year old male who presented to the emergency department (ED) with three days of progressively severe and constant mid-epigastric abdominal pain. On evaluation, he was found to have elevated lipase levels. Computed tomography (CT) scan of his abdomen revealed findings consistent with pancreatitis without any evidence of gallstones or common bile duct dilation. He denied alcohol use, trauma, and insect bites or stings. His calcium and triglyceride levels were within normal limits. His blood cultures did not show any bacterial growth. He had recently been initiated on doxycycline for concerns of cellulitis and had begun to develop abdominal pain seven days after the initiation of doxycycline. He had completed his antibiotic course on the day of presentation to the ED. He had no other recent medication changes. He had subsequent improvement of symptoms off of the doxycycline and with supportive care. Given that all other causes of pancreatitis had been excluded and that he had been initiated on doxycycline prior to presentation, the etiology was attributed to being likely secondary to doxycycline use. Our case highlights the importance of reviewing outpatient medications by the hospital medicine team and awareness of rare triggers for acute pancreatitis.


Synthesis and fungicidal activities of novel bis(trifluoromethyl)phenyl-based strobilurins.
Strobilurins have become one of the most important classes of agricultural fungicides. To search for novel strobilurin compounds with unique biological activities, novel bis(trifluoromethyl)phenyl-based strobilurin analogues were synthesized by the reaction of 1-bis(trifluoromethyl)phenyl based methanone oxime with corresponding strobilurin pharmacophores in the presence of bases such as potassium hydroxide, potassium carbonate, or sodium hydride. ( E)-Methyl 2-(2-(((( Z)(1-(3,5-bis(trifluoromethyl) phenyl)-1-methoxymethylidene)amino)oxy)methyl)phenyl)-3-methoxyacrylate and ( Z)-methyl- N-( E)-2-(( E)-(5,6-dihydro-1,4,2-dioxazin-3-yl)(methoxyimino)methyl)benzyloxy-3,5-bis(trifluoromethyl)benzimidate were more effective against Erysiphe graminis and sphaerotheca fuligine than commercial strobilurin fungicides metominostrobin, azoxystrobin, and trifloxystrobin.


Diagonal earlobe crease: a coronary risk factor, a genetic marker of coronary heart disease, or a mere wrinkle. Ancient Greco-Roman evidence.
In a new study on the relationship between the diagonal earlobe crease (DELC), first described by Frank in 1973, and the presence of chronic ischemic heart disease, four main hypotheses are presented. Hypothesis 1: DELC is a coronary risk factor or a marker of coronary risk factor. Hypothesis 2: DELC is a genetic marker of atherosclerotic coronary disease. Hypothesis 3: DELC is, in fact, the result of aging and the relationship with atherosclerotic coronary disease is mere coincidence. Hypothesis 4: DELC is an anatomic peculiarity of the ear lobe, perhaps the result of a particular way of sleeping. These hypotheses are discussed in the light of the most important results obtained so far, in the literature and in the author's personal studies. Moreover, the data reported by Petrakis, who was the first to mention in 1980 the presence of this sign in some of the Greco-Roman sculptures in the museums of Rome, are corroborated by the observations of one of the authors, made in the Louvre Museum in Paris.


Puromycin inhibition of cholesterol absorption in the rat.
The effect of puromycin on the intestinal absorption of cholesterol has been studied in rats with indwelling catheters in the left thoracic lymphatic duct. Puromycin administration to female rats produced a marked depression of cholesterol absorption under conditions where the absorption of simultaneously administered fatty acid was also dramatically inhibited. The same treatment of male rats also produced a significant depression in cholesterol absorption, but was without effect on absorption of the fatty acid. Despite the depressions of lipid absorption in puromycin-treated animals, there was no accumlation of either cholesterol or fatty acid in the intestinal mucosa of either sex. Actinomycin D treatment of fasting male and female rats, receiving constant infusions of saline, had no effect on the rate of lymph production. This suggest that altered lymph production was not responsible for the depressed lipid absorption observed in fed animals treated with protein synthesis inhibitors. The selective inhibition of cholesterol absorption in male rats also precludes the possibility that the major effect of the inhibitor is on delayed gastric emptying.


Conformational changes and allosteric communications in human serum albumin due to ligand binding.
It is well recognized that knowledge of structure alone is not sufficient to understand the fundamental mechanism of biomolecular recognition. Information of dynamics is necessary to describe motions involving relevant conformational states of functional importance. We carried out principal component analysis (PCA) of structural ensemble, derived from 84 crystal structures of human serum albumin (HSA) with different ligands and/or different conditions, to identify the functionally important collective motions, and compared with the motions along the low-frequency modes obtained from normal mode analysis of the elastic network model (ENM) of unliganded HSA. Significant overlap is observed in the collective motions derived from PCA and ENM. PCA and ENM analysis revealed that ligand selects the most favored conformation from accessible equilibrium structures of unliganded HSA. Further, we analyzed dynamic network obtained from molecular dynamics simulations of unliganded HSA and fatty acids- bound HSA. Our results show that fatty acids-bound HSA has more robust community network with several routes to communicate among different parts of the protein. Critical nodes (residues) identified from dynamic network analysis are in good agreement with allosteric residues obtained from sequence-based statistical coupling analysis method. This work underscores the importance of intrinsic structural dynamics of proteins in ligand recognition and can be utilized for the development of novel drugs with optimum activity.


High-frequency-based features for low and high retina haemorrhage classification.
Haemorrhages (HAs) presence in fundus images is one of the most important indicators of diabetic retinopathy that causes blindness. In this regard, accurate grading of HAs in fundus images is crucial for appropriate medical treatment. The purpose of this Letter is to assess the relative performance of statistical features obtained with three different multi-resolution analysis (MRA) techniques and fed to support vector machine in grading retinal HAs. Considered MRA techniques are the common discrete wavelet transform (DWT), empirical mode decomposition (EMD), and variational mode decomposition (VMD). The obtained experimental results show that statistical features obtained by EMD, VMD, and DWT, respectively, achieved 88.31% ± 0.0832, 71% ± 0.1782, and 64% ± 0.0949 accuracies. It also outperformed VMD and DWT in terms of sensitivity and specificity. Thus, the EMD-based features are promising for grading retinal HAs.


Natural compounds based chemotherapeutic against Chagas disease and leishmaniasis: mitochondrion as a strategic target.
Over the past years, natural products have been explored in order to find biological active substances to treat various diseases. Regarding their potential action against parasites such as trypanosomatids, specially Trypanosoma cruzi and Leishmania spp., much advance has been achieved. Extracts and purified molecules of several species from genera Piper, Tanacetum, Porophyllum, and Copaifera have been widely investigated by our research group and exhibited interesting antitrypanosomal and antileishmanial activities. These natural compounds affected different structures in parasites, and we believe that the mitochondrion is a strategic target to induce parasite death. Considering that these trypanosomatids have a unique mitochondrion, this cellular target has been extensively studied aiming to find more selective drugs, since the current treatment of these neglected tropical diseases has some challenges such as high toxicity and prolonged treatment time. Here, we summarise some results obtained with natural products from our research group and we further highlighted some strategies that must be considered to finally develop an effective chemotherapeutic agent against these parasites.


Impact on Patient Safety Culture by the Intervention of Multidisciplinary Medical Teams.
To provide comprehensive patient-centered care, we need multidisciplinary teams to face challenges of advanced and complex care. The Taichung Veterans General Hospital has had a ward-based multidisciplinary team system in each ward for 10 years. This study aimed to investigate whether better team performance results in a more positive response in patient safety culture (PSC). From 2014 to 2017, there were 21 ward-based multidisciplinary teams. We organized an evaluation panel to assess the performance of the teams. Those teams were divided into 3 groups: high, medium, and low according to their annual performance scores. The Taichung Veterans General Hospital used annual Safety Attitude Questionnaire-based surveys concerning patient safety issues. We used the generalized estimating equation to analyze the dataset over 4 years. All analyses were carried out using SAS Version 9.4 (SAS Institute, Cary, NC). Taking the trend effects from 2014 to 2017 into account, we found that teamwork climate, safety climate, and perception of management were significantly better in the high and medium groups of the ward-based multidisciplinary teams. There was no significant difference in the dimensions of job satisfaction, stress recognition, and working conditions, which suggests that all staff had the same degree of stress or work loading. Our ward-based multidisciplinary team system had a positive effect on PSC, which demonstrates the following: when team performance is better, patient safety climate is also better. We should keep the ward-based multidisciplinary team system, improve its performance, and maximize positive attitudes about PSC among our staff.


Adding fuel to the fire? Revegetation influences wildfire size and intensity.
The regrowth of woody vegetation in cleared landscapes (i.e. revegetation) has the potential to dramatically alter the spatial characteristics of vegetation and fuels, which will potentially alter fire characteristics. Understanding how revegetation alters fire size and intensity will be critical in determining the social and environmental value of revegetation. We used simulation modelling to examine (i) whether increasing native woody vegetation extent across landscapes cleared for pasture (i.e. revegetation) affects fire size and median fireline intensity and (ii) whether fuel load in the pasture matrix, the initial extent of land clearing and weather conditions during a fire alter the direction and/or magnitude of the relationships between revegetation and fire size or intensity. Simulations revealed that fire size and intensity were altered by increasing woody vegetation extent, though the direction of change was dependent upon landscape context. Increased woody vegetation extent led to (i) increased fire size in landscapes with low pasture fuel load (2 t ha(-1)) regardless of the extent of land clearing, (ii) decreased fire size in highly cleared landscapes with moderate (4.5 t ha(-1)) and high (7 t ha(-1)) pasture fuel load, and (iii) little change to fire size in landscapes subjected to low levels of clearing when pasture fuel load was moderate or high. Similar patterns were observed for fireline intensity. The magnitude of change in fire size and intensity was greatest under extreme fire weather conditions. Revegetation rarely increased median fireline intensity beyond suppressible levels (i.e. 4000 kW m(-1)), with fire weather and pasture fuel load being the main determinants of suppression potential. Our findings show that the response of fire size and intensity to revegetation will depend on landscape scale pasture management.


[Radioimmunotherapy with yttrium-90 ibritumomab tiuxetan. Clinical considerations, radiopharmacy, radiation protection, perspectives].
90Y-ibritumomab tiuxetan (Zevalin) is currently approved for radioimmunotherapy of patients with relapsed or refractory follicular non-Hodgkin's lymphoma pretreated with rituximab. Future directions are the combined use of 90Y-ibritumomab tiuxetan as part of the initial treatment and as first-line multi-agent therapy of relapsed disease. Current studies investigate patients with other than follicular indolent histologies, e. g. diffuse large cell lymphoma. Labelling of 90Y ibritumomab tiuxetan is a safe procedure, the radiochemical purity is not disturbed by a higher room temperature or by metallic impurity. Quality control is recommended by thin layer chromatography (TLC), strips >15 cm are favourable. TLC cannot distinguish between the correctly radiolabelled antibodies and radiocolloid impurity. If necessary, additional HPLC should be performed. Radiocolloid impurities are absorbed to the solid phase and do not reach the eluate. If the radiochemical purity test is insufficient (<95%), the additional cleaning using EconoPac 10 DG columns (Biorad, Hercules, CA, USA) is a reliable procedure to reduce the percentage of free radionuclide. However, this procedure is not part of the approval.


Loss of Smad3-mediated negative regulation of Runx2 activity leads to an alteration in cell fate determination.
Runx2 is required for osteoblast differentiation but is expressed in certain nonosteoblastic cells without activating the differentiation process, suggesting that its activity is suppressed through a lineage-specific mechanism. Here we report that primary mouse dermal fibroblasts lacking Smad3 can acquire an osteoblast-like phenotype, including activation of Runx2 activity, expression of osteoblast-specific genes, and calcium deposition. We further show that negative regulation of Runx2 activity by Smad3 in dermal fibroblasts is likely mediated by controlling the expression of Msx2, an antagonist of Runx2 in this cellular context. These data support the presence of a novel mechanism for controlling cell fate determination of mesenchymal lineages by preventing differentiation toward the osteoblastic lineage via negative regulation of Runx2 activity.


Ancient landscapes and the relationship with microbial nitrification.
Ammonia oxidizing archaea (AOA) and bacteria (AOB) drive nitrification and their population dynamics impact directly on the global nitrogen cycle. AOA predominate in the majority of soils but an increasing number of studies have found that nitrification is largely attributed to AOB. The reasons for this remain poorly understood. Here, amoA gene abundance was used to study the distribution of AOA and AOB in agricultural soils on different parent materials and in contrasting geologic landscapes across Australia (n = 135 sites). AOA and AOB abundances separated according to the geologic age of the parent rock with AOB higher in the more weathered, semi-arid soils of Western Australia. AOA dominated the younger, higher pH soils of Eastern Australia, independent of any effect of land management and fertilization. This differentiation reflects the age of the underlying parent material and has implications for our understanding of global patterns of nitrification and soil microbial diversity. Western Australian soils are derived from weathered archaean laterite and are acidic and copper deficient. Copper is a co-factor in the oxidation of ammonia by AOA but not AOB. Thus, copper deficiency could explain the unexpectedly low populations of AOA in Western Australian soils.


Niemann-Pick type C disease.
A 4-year-old Afghan girl born to consanguineous parents presented with progressive neurological regression and hepatomegaly noticed after one year of age. The child had hypotonia, repeated unexplained falls and facial dyskinesia. Bone marrow examination revealed presence of storage cells suggestive of Gauchers or Niemann Pick. Confirmatory study by lysosomal enzyme from leucocytes was normal for beta-Glucosidase and sphingomyelinase specific for Gauchers and Niemann Pick type A or B respectively. Further study was carried out on cultured skin fibroblasts in lipid deficient medium using filipin stain which showed presence of dark punctate granules confirming the diagnosis of Neimann-Pick type C, a rare autosomal recessive disorder.


Trends in pain relief in labour: implications for obstetric analgesia service in Nigeria.
Labour and delivery result in severe pain for most women. Attention to comfort and analgesia for women in labour is important for physiological reasons and out of compassion. A review of common methods of pain relief of labour was done. Inhalation method as well as intravenous administration of opioids for pain relief in labour is fast giving way to lumbar epidural analgesia. The use of local anaesthetic in labour offers superior pain relief, is effective and safe. The inhalation and parenteral routes seem reserved for patients with contraindication to insertion of epidural. The administration of high volume dilute concentration of local anaesthetic plus lipid soluble opioids, with some level of patient's control, appears to be the current trend in the management of labour pains. There is a body of evidence indicating that Nigerian women may want pain relief in labour. However, there is no organised labour analgesia service in Nigeria. An organised obstetric analgesia service can be developed within the limits of available manpower and technology in an emerging country like Nigeria. This article therefore, focuses on trends in obstetric analgesia and its implications on the development of organised obstetric analgesia services in Nigeria. Key words: obstetric analgesia, obstetric analgesia service, Nigeria.


Lumbar spine fusion outcomes using a cellular bone allograft with lineage-committed bone-forming cells in 96 patients.
Instrumented posterior lumbar fusion (IPLF) with and without transforaminal interbody fusion (TLIF) is a common treatment for low back pain when conservative interventions have failed. Certain patient comorbidities and lifestyle risk factors, such as obesity and smoking, are known to negatively affect these procedures. An advanced cellular bone allograft (CBA) with viable osteogenic cells (V-CBA) has demonstrated high fusion rates, but the rates for patients with severe and/or multiple comorbidities remain understudied. The purpose of this study was to assess fusion outcomes in patients undergoing IPLF/TLIF using V-CBA with baseline comorbidities and lifestyle risk factors known to negatively affect bone fusion. This was a retrospective study of de-identified data from consecutive patients at an academic medical center who underwent IPLF procedures with or without TLIF, and with V-CBA. Baseline patient and procedure characteristics were assessed. Radiological outcomes included fusion rates per the Lenke scale. Patient-reported clinical outcomes were evaluated via the Oswestry Disability Index (ODI) and Visual Analog Scale (VAS) for back and leg pain. Operating room (OR) times and intraoperative blood loss rates were also assessed. Data from 96 patients were assessed with a total of 222 levels treated overall (mean: 2.3 levels) and a median follow-up time of 16 months (range: 6 to 45 months). Successful fusion (Lenke A or B) was reported for 88 of 96 patients (91.7%) overall, including in all IPLF-only patients. Of 22 patients with diabetes in the IPLF+TLIF group, fusion was reported in 20 patients (90.9%). In IPLF+TLIF patients currently using tobacco (n = 19), fusion was reported in 16 patients (84.3%), while in those with a history of tobacco use (n = 53), fusion was observed in 48 patients (90.6%). Successful fusion was reported in all 6 patients overall with previous pseudarthrosis at the same level. Mean postoperative ODI and VAS scores were significantly reduced versus preoperative ratings. The results of this study suggest that V-CBA consistently yields successful fusion and significant decreases in patient-reported ODI and VAS, despite patient comorbidities and lifestyle risk factors that are known to negatively affect such bony healing.