One-dimensional Cu(II) coordination polymers containing C2h-symmetric 1,1':4',1''-terphenyl-3,3'-dicarboxylate linkers.
Two new one-dimensional Cu(II) coordination polymers (CPs) containing the C2h-symmetric terphenyl-based dicarboxylate linker 1,1':4',1''-terphenyl-3,3'-dicarboxylate (3,3'-TPDC), namely catena-poly[[bis(dimethylamine-κN)copper(II)]-μ-1,1':4',1''-terphenyl-3,3'-dicarboxylato-κ(4)O,O':O'':O'''] monohydrate], {[Cu(C20H12O4)(C2H7N)2]·H2O}n, (I), and catena-poly[[aquabis(dimethylamine-κN)copper(II)]-μ-1,1':4',1''-terphenyl-3,3'-dicarboxylato-κ(2)O(3):O(3')] monohydrate], {[Cu(C20H12O4)(C2H7N)2(H2O)]·H2O}n, (II), were both obtained from two different methods of preparation: one reaction was performed in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) as a potential pillar ligand and the other was carried out in the absence of the DABCO pillar. Both reactions afforded crystals of different colours, i.e. violet plates for (I) and blue needles for (II), both of which were analysed by X-ray crystallography. The 3,3'-TPDC bridging ligands coordinate the Cu(II) ions in asymmetric chelating modes in (I) and in monodenate binding modes in (II), forming one-dimensional chains in each case. Both coordination polymers contain two coordinated dimethylamine ligands in mutually trans positions, and there is an additional aqua ligand in (II). The solvent water molecules are involved in hydrogen bonds between the one-dimensional coordination polymer chains, forming a two-dimensional network in (I) and a three-dimensional network in (II).


Ultrastructure of the midgut of Phrixocephalus cincinnatus (Wilson), a blood-feeding parasitic copepod of flatfishes.
Phrixocephalus cincinnatus is a blood-feeding copepod parasite inhabiting the choroid of the eye of the Pacific sanddab Citharichthys sordidus off the coast of southern California. The present study examined the fine structure of the midgut using both light and electron microscopy. The anterior midgut or stomach was lined with a tall columnar epithelium. The apical surfaces of the cells formed vesicles that pinched off and entered the gut lumen. Posteriorly, the midgut consisted of 2 morphologically distinct cell types; vacuolar and nonvacuolar. These cells probably were different developmental and functional stages of a single kind of columnar epithelial cell. The nonvacuolar cells possessed basally located nuclei, rough endoplasmic reticulum, and long microvilli indicative of an absorptive function. The vacuolar cells were characterized by short microvilli, endocytic vesicles, primary and secondary lysosomes, well-developed rough endoplasmic reticulum, and Golgi apparatus, suggesting that they were active in endocytosis as well as the synthesis of digestive and lysosomal enzymes. Distension of the apical surface of vacuolar cells with enzyme-containing vesicles resulted in the liberation of the distal part of the cell into the gut lumen. Subsequent lysis of the cell membrane released enzyme-containing vesicles, suggesting that digestive enzymes are discharged by apocrine secretion of the vacuolar cells. Both vacuolar and nonvacuolar cells absorb nutrients resulting from the extracellular digestion of host blood.


Effects of erythromycin, clarithromycin and rokitamycin on nifedipine metabolism in rats.
The effects of erythromycin, clarithromycin and rokitamycin on the metabolism of nifedipine were studied in vitro and in situ. Erythromycin, clarithromycin or rokitamycin added to nifedipine did not inhibit the formation of metabolite, M-1, of nifedipine, whereas pretreatment with erythromycin or clarithromycin significantly (p < 0.05) inhibited its formation. Only erythromycin significantly (p < 0.05) inhibited the formation of M-2 from M-1. These observations agreed with the results obtained using an in situ rat intestinal loop technique. As assessed by the concentrations of nifedipine and M-2 in jugular and portal vein blood, the inhibition of nifedipine metabolism by erythromycin was greater after multiple doses than after a single dose. Moreover, our results suggest that rokitamycin is a less potent inhibitor of nifedipine metabolism.


Exploration of Online Culture Through Network Analysis of Wikipedia.
Understanding online culture is becoming crucial in the global and connected world. Contrary to conventional attitudinal surveys used in cultural research, this study uses the approach of directly observing culture-specific behavior that emerges from online collaboration on the Internet. The editing data of Wikipedia were analyzed in 12 languages. Distinctive cultural dimensions were identified, including collectivism, extraversion, boldness, and egalitarianism. Using network analysis, the language-framed cultural factors were extracted as an emergent phenomenon in the virtual world.


A comparative analysis of two dosing strategies of flurbiprofen in rheumatoid arthritis: an application of sequential trial design.
Forty patients with classic or definite rheumatoid arthritis were entered into a double-blind, randomized, multiple crossover, sequential trial comparing two doses (300 mg vs 150 mg per day) and two dosing schedules (b.i.d. vs t.i.d.) of flurbiprofen. Clinical assessments (Ritchie Index, grip strength, walking time, physician and patient global assessments) were made at baseline and at biweekly intervals during the next six weeks of active treatment. Overall there were no statistically significant differences either between the two dosage levels or the dosing schedules. This study demonstrates the utility of the sequential trial design in assessing drug efficacy. The data confirm a lack of difference between the two doses of flurbiprofen selected and suggest that twice-daily dosing with flurbiprofen is similar in efficacy to thrice-daily dosing.


Block of ATP-regulated potassium channels by phentolamine and other alpha-adrenoceptor antagonists.
1. The patch clamp technique has been used to characterize the effects of phentolamine, an unselective blocker of alpha 1- and alpha 2-adrenoceptors, on the electrical activity of isolated RINm5F insulin-secreting cells and the gating of ATP-regulated potassium (K+ATP) channels. 2. Current-clamp experiments carried out by use of both conventional whole-cell recordings and nystatin-perforated cells, have demonstrated that phentolamine (5-20 microM) in the complete absence of alpha-adrenoceptor agonists, caused a sharp depolarization of the cell membrane from approximately -66 mV to -42 mV. This depolarization was associated with the generation of calcium action potential-like spikes. In the continued presence of phentolamine, diazoxide (100 microM) reversed these effects by causing a hyperpolarization of the cell, thereby preventing Ca2+ spikes. 3. Unitary current events from K+ATP channels were recorded from both outside-out membrane patches and saponin permeabilized or open-cells. When added to either the inside or the outside of the plasma membrane, phentolamine (0.1-100 microM) blocked openings from these channels. The effects of phentolamine were rapid, sustained and fully reversible. Phentolamine was apparently a more effective blocker of channels from the inside than the outside of the membrane. 4. The KI value, corresponding to 50% inhibition of channels was estimated to be approximately 0.7 microM when phentolamine was added to the inside of the membrane and the Hill coefficient approximately 1. 5. Yohimbine (1-10 microM) and the chemically 2-substituted imidazoline alpha-adrenoceptor antagonists, antazoline (25 microM) and tolazoline (25 microM) were also found to block K+ATP channels in isolated patches of membrane. 6. In conclusion the present study demonstrates that phentolamine and other imidazoline adrenoceptor antagonists have effects upon ATP-sensitive K+ channels that are not associated with stimulation of the adrenoceptor.


Ongoing 5-year+ survival after multiple metastasectomies, followed by CAPOX plus bevacizumab, for metastatic colorectal cancer.
Advancements in chemotherapy for metastatic colorectal cancer (mCRC) have improved long-term outcomes, and median survival currently exceeds 30 months. The recommended treatment for mCRC is multidisciplinary, including a combination of surgical resection and chemotherapy. In this study, we report the case of a patient who has survived for more than 5 years after an initial diagnosis of mCRC while undergoing first-line chemotherapy and six repeat metastasectomies. A 55-year-old man was diagnosed at our hospital with sigmoid colon cancer and hepatic metastasis. We performed laparoscopic sigmoidectomy and hepatic segmentectomy (segment 5 [S5] and S8). After resecting the primary tumor and liver metastasis, other metastases were found. Together with perioperative chemotherapy (CAPOX + bevacizumab), we performed repeated metastasectomies for liver metastasis (S4 and S7), pulmonary S1 metastasis, aortic lymph node metastasis, and right adrenal metastasis. With six metastasectomies, the patient has survived for more than 5.5 years. Multidisciplinary treatment extends survival and improves the quality of life in patients with mCRC. Planned surveillance after metastasectomy may also be necessary to promote the early detection of recurrence in these patients.


'Palatal swelling in a patient suffering from filariasis'.
Sclerosing mucoepidermoid carcinoma (SMEC) is a distinct but an uncommon salivary gland neoplasm with only 19 cases reported in English literature till date. Densely collagenous sclerotic stroma, resemblance to other benign lesions and rarity of this tumour often makes the diagnosis of SMEC challenging. Here we report a case of SMEC in a 73-year old female patient suffering from filariasis. Clinical, radiological, fine needle aspiration biopsy, gross and histopathological features are discussed with detailed review of literature and probable pathogenesis.


Revision of the subgenus Dicranomyia (Erostrata) Savchenko, 1976 (Diptera, Limoniidae) of Japan.
The six Japanese species of the subgenus Dicranomyia (Erostrata) Savchenko, 1976 are revised. D. (E.) globithorax Osten Sacken, 1869 and D. (E.) tabashii (Alexander, 1934) are newly recorded from Japan. We elevate the two subspecies of D. globithorax to species rank based on distinct morphological differences. Three new species, D. (E.) reniformis sp. nov., D. (E.) submelas sp. nov., and D. (E.) yazuensis sp. nov. are described. The male genitalia of all Japanese species and female ovipositors of four of the six species are illustrated, and the habitus of adults are photographed. A key to the Japanese species of the subgenus is provided.


Collection development policies and practices in medical school rare book libraries.
A survey of collection development policies and practices in medical school rare book libraries indicated that only 20% had documented criteria for collection development. The advantages of preparing and maintaining a formal written collection development policy are presented with guidelines for formulating such a policy.


New Route to Stabilize Ruthenium Nanoparticles with Non-Isolable Chiral N-Heterocyclic Carbenes.
Ru nanoparticles (RuNPs) stabilized by non-isolable chiral N-heterocyclic carbenes (NHCs), namely SIDPhNp ((4S,5S)-1,3-di(naphthalen-1-yl)-4,5-diphenylimidazolidine) and SIPhOH ((S)-3-((1S,2R)-2-hydroxy-1,2-diphenylethyl)-1-((R)-2-hydroxy-1,2-diphenylethyl)-4,5-dihydro-3H-imidazoline), have been synthesized through a new procedure that does not require isolation of the free carbenes. The obtained RuNPs have been characterized by state-of-the-art techniques and their surface chemistry has been investigated by FTIR and solid-state MAS NMR upon the coordination of CO, which indicated the presence of free and reactive Ru sites. Their catalytic activity has been tested in various hydrogenation reactions involving competition between different sites, whereby interesting differences in selectivity were observed, but no enantioselectivity.


[A Case of Retroperitoneal Cavernous Hemangioma Difficult to Differentiate from Retroperitoneal Liposarcoma].
We report a case of retroperitoneal cavernous hemangioma. A 77-year-old woman complaining of nausea was admitted to a different hospital in September 2013. Computed tomography (CT) detected a retroperitoneal mass in the left pararenal space. Three years later, repeated CT showed that the tumor had gradually grown in size. On dynamic contrast-enhanced magnetic resonance imaging (MRI), the tumor demonstrated radiographic signs of a liposarcoma. Resection of the mass with left nephrectomy was performed in June 2016, and histopathology showed cavernous hemangioma. Clinical diagnosis of cavernous hemangioma is difficult, and imaging modalities, including CT and MRI, may not be conclusive. The final diagnosis in most cases is established through surgery. This is the 29th case of retroperitoneal cavernous hemangioma to be reported in Japan.


[Histologic diagnosis of rejection after heart transplantation].
The author reconsiders Stanford classification which separates 3 degrees of rejection of transplanted hearts: minimal, moderate or severe rejection. This classification, widely used, was enriched with J. Kennitz's sub-varieties, based on more than 4,000 endomyocardial biopsies, performed on 132 patients who underwent heart transplantation. Interpretation of the histopathologic results of endomyocardial biopsies requires careful knowledge of simultaneous clinical or biochemical data. However, heart biopsy remains indispensible since it is the only test providing information on the presence or absence of cellular infiltrate and on myocardial fibers changes. The difficulties result from the very small size of all samples. Several types of rejection are illustrated and commented. However, the author's experience is presently restricted and hardly allows separating moderate rejections from minimal or severe rejections.


[Remarks on ECG changes during and following stress].
In order to obtain a relatively comprehensive picture of the functional capacity of the heart it is absolutely necessary to perform examinations under dynamic stress. The evaluation of an ECG during and immediately following ergometric stress presupposes a knowledge of the normal ECG pattern and also the characteristic pathological reactions. The ST changes and rhythm disturbances demand special attention. This article covers the most common normal and pathological patterns in addition to discussing several particular aspects of electrocardiograms taken during and after stress as well as their clinical importance.


Effective onion vinegar production by a two-step fermentation system.
A two-step fermentation system combining a repeated batch process using a flocculating yeast with a charcoal pellet bioreactor was developed for onion vinegar production. Juice from the red onion R-3, which contained 67.3 g/l total sugar, was smoothly converted to onion alcohol containing 30.6 g/l ethanol by repeated batch operation using the flocculating yeast Saccharomyces cerevisiae strain IR-2. Stable operation was possible and the maximum productivity was about 8.0 g/l/h. A packed bed bioreactor containing charcoal pellets produced from waste mushroom medium was then applied to continuous onion vinegar production from the onion alcohol. Onion vinegar was successfully produced, with a maximum productivity and acetic acid concentration of about 3.3 g/l/h and 37.9 g/l, respectively. The total acetic acid yield calculated from the amount of sugar consumed was 0.86. The two-step system was operated for 50 d and proved to be competitive with other systems in terms of its high productivity, high acetic acid yield, operational stability and low production costs.


A Both-End Blocked Peroxidase-Mimicking DNAzyme for Low-Background Chemiluminescent Sensing of miRNA.
G-quadruplex DNAzymes that exhibited peroxidase-like activity have been shown to be appealing reporters for amplified readout of biosensing events simply by their formation or dissociation in the presence of analytes. For low background signaling, the efficient preblock of DNAzymes is critically important. Herein, we report a both-end blocked DNAzyme beacon strategy for chemiluminescent biosensing. The catalytic activity of peroxidase-mimicking DNAzyme can be inactivated fully by fixing both ends of the DNAzyme sequence, and easily recovered via a strand displace reaction between the miRNA and the block DNA. The efficient block and recovery of DNAzymes provide the both-end blocked beacon the highest signal-to-background ratio (over 25) among the reported DNAzymes for amplification-free detection of miRNA. As a result, the beacon allowed detection of subpicomolar miRNA without any labeling and amplification procedures, which is about 40-fold more sensitive than the traditional hairpin fluorescence beacon. Also, it exhibited excellent discrimination ability that can distinguish single-base mismatch miRNA. The simplicity, high sensitivity, and selectivity provided by the beacon make it a promising alternative tool for nucleic acid detection.


Interdependence of baseline correction method and covariance structure for crossover TQT studies.
Thorough QT/QTc (TQT) trials are conducted to assess a drug's risk potential for prolonging the QT interval. In a randomized crossover, multiple postdose electrocardiograph (ECG) readings are collected over time, within each period leading to a repeated-measures scenario. Additionally, baseline readings at single or multiple time points are collected prior to treatment. Two active, yet seemingly separate, areas of statistical research for TQT crossover studies concern the method of baseline correction and the specified covariance structure for repeated measures analysis. Due to interdependence of the covariance structure of baseline-corrected QTc values and the definition of baseline, these two research areas cannot be considered separately. We illustrate how the covariance structure for baseline-corrected QTc values differs under various definitions of baseline and provide recommendations on the choice of baseline: Time-matched baseline averaged over periods and time-matched baseline from the first period only are preferable in terms of efficiency; in case a period-specific correction is required to account for the treatment carryover effect, period-specific time-averaged baseline with multiple measurements taken predose in each period offers greater efficiency than a single predose baseline. This research on the interdependence of baseline correction method and covariance structure enables statisticians to use observed data from previous TQT studies to plan design and analysis for future studies.


Bryostatin 1/ionomycin (B/I) ex vivo stimulation preferentially activates L-selectinlow tumor-sensitized lymphocytes.
We have shown that tumor vaccine-sensitized draining lymph node (vDLN) cells activated ex vivo with bryostatin and ionomycin (B/I) were capable of inducing antigen-specific regression of a murine mammary tumor, 4T07. vDLN cells not activated with B/I were ineffective. We hypothesized that B/I selectively activates tumor-sensitized (CD62Llow) lymphocytes, to account for the highly potent and tumor-specific activity. We hypothesized that CD8+ CD62Llow cells may be preferentially activated by B/I treatment, infiltrate the tumors and mediate tumor regression in mice. 4T07-IL2 tumor cells were injected into one hind footpad of BALB/c mice. Ten days later, vDLN were harvested and separated based on CD62L expression. After separation, cells were activated with B/I, expanded with IL2 (40 IU/ml) for 10 days, and adoptively transferred to 4T07 tumor bearing mice. Naive mice were also treated with different subsets of T cells and later were challenged with 4T07 tumor cells. To test in vitro responses to antigen, expanded lymphocytes were cultured either alone or with irradiated 4T07 tumor cells. Supernatants were harvested after 24 h and tested by ELISA for IFN-gamma. The importance of the host immune response was tested by AIT into 4T07-bearing nude athymic mice. Host mice were depleted in vivo of CD4 or CD8 T cells after vDLN AIT to ascertain the mediators of tumor regression. In order to track B/I activated vDLN cells, they were prestained with CFSE prior to adoptive transfer into tumor-bearing hosts. At various time points, tumors, spleens and lymph nodes of host mice were harvested, dual stained for activation marker expression and analyzed by flow cytometry. CD62Llow cells expanded 12-fold more than CD62Lhigh lymphocytes during the 10 day culture period. Supernatant from CD62Llow cells + 4T07 cultures contained 33-fold more IFN-gamma than supernatant from CD62Lhigh cells + 4T07 cultures (843.9 pg/ml +/- 135.8 vs 25.89 pg/ml +/- 0.01). Adoptive transfer of CD62Llow lymphocytes induced complete tumor regressions in all mice, while tumors regressed in only 17% of mice treated with CD62Lhigh lymphocytes. Naive mice that received B/I-activated CD62Llow cells were protected from future tumor challenges, while mice given CD62Lhigh cells did not exhibit the same resistance to tumor growth. Tumors in nude host mice regressed after AIT treatment. In vivo depletion of CD4 T cells after AIT did not inhibit tumor regression, but CD8 T cell depletion abrogated tumor regression. vDLN cells tracked preferentially to tumor draining lymph nodes and proliferated in vivo, persisting for at least 21 days, and were 95% CD44+ and 39% CD69+. Bryostatin 1 and ionomycin, by increasing PKC activity and intracellular calcium, respectively, mimic intracellular signals that result in T cell activation. CD62Llow cells are preferentially activated by B/I, leading to a highly effective anti-tumor T cell population.


Groundwater level observations in 250,000 coastal US wells reveal scope of potential seawater intrusion.
Seawater intrusion into coastal aquifers can increase groundwater salinity beyond potable levels, endangering access to freshwater for millions of people. Seawater intrusion is particularly likely where water tables lie below sea level, but can also arise from groundwater pumping in some coastal aquifers with water tables above sea level. Nevertheless, no nation-wide, observation-based assessment of the scope of potential seawater intrusion exists. Here we compile and analyze ~250,000 coastal groundwater-level observations made since the year 2000 in the contiguous United States. We show that the majority of observed groundwater levels lie below sea level along more than 15% of the contiguous coastline. We conclude that landward hydraulic gradients characterize a substantial fraction of the East Coast (>18%) and Gulf Coast (>17%), and also parts of the West Coast where groundwater pumping is high. Sea level rise, coastal land subsidence, and increasing water demands will exacerbate the threat of seawater intrusion.


Dermal Autograft Using Donor Breast as Alternative to Acellular Dermal Matrices in Tissue Expander Breast Reconstruction: A Comparative Review.
Shifting preference for implant-based breast reconstruction has resulted in an increased use of acellular dermal matrix (ADM) in tissue-expander breast reconstruction. The benefits afforded by ADM must be weighed against a potential increased risk for postoperative complications. Dermal autograft-assisted breast reconstruction using autograft harvest from the lower abdomen has been shown to result in equivalent aesthetics and patient satisfaction compared with ADM at a lower cost, with fewer complications. The purpose of this study was to review a series of patients who underwent bilateral mastectomy and immediate dermal autograft-assisted tissue expander (TE) breast reconstruction using the non-cancerous breast as a donor site, comparing the outcomes with a concurrent cohort of patients undergoing ADM-assisted reconstruction to determine the relative safety, cost, and effectiveness of the 2 procedures. The study population included all patients who underwent dermal autograft-assisted TE breast reconstruction, using the contralateral cancer-free breast as the source of dermal autograft, between 2010 and 2015. The ADM cohort consisted of patients who underwent bilateral mastectomy and immediate ADM-assisted TE breast reconstruction during the same period. Univariate analysis was performed for demographic data, complications, operative cost, and operative time. Data were compared using the Wilcoxon rank sum test for nonparametric data and χ analyses for continuous and categorical variables. Significance was defined as P value less than 0.05. Seventeen patients received dermal autograft using the non-cancerous breast donor site. Twenty-seven patients who underwent ADM-assisted reconstruction during the same period were identified. Significantly higher cost was demonstrated between groups (ADM, US $9999.87; autograft, US $3924.19; P < 0.0001). No significance difference existed operative time (autograft, 97 min; ADM, 120 min). No difference was found in wound healing complications (ADM, 14.8%; autograft, 23.53%; P = 0.47). No significant difference was found in major complications (ADM, 26%; autograft, 17.65%; P = 0.52) or infectious complications (ADM, 26%; autograft, 17.65%; P = 0.52). Dermal autograft-assisted breast reconstruction using the contralateral non-cancerous breast as the source of dermal autograft harvest represents a lower cost alternative to ADM without increased risk of postoperative complications.


Cheilitis granulomatosa Miescher: treatment with clofazimine and review of the literature.
Cheilitis granulomatosa Miescher is a rare condition of unknown cause characterized by intermittent lip swelling that gradually persists and causes cosmetic deformity. We report the case of a young woman with cheilitis granulomatosa as a monosymptomatic manifestation of Melkersson-Rosenthal syndrome successfully treated by the antileprosy agent clofazimine, and propose clofazimine as an alternative treatment in cases refractory to corticosteroids. The differential diagnosis and current methods of treatment are summarized, and the literature is reviewed and discussed.


Changing the recognition site of a conjugative relaxase by rational design.
TrwC is a relaxase protein, which starts and finishes DNA processing during bacterial conjugation in plasmid R388. TrwC recognizes a specific sequence of DNA (25 nucleotides) in the donor cell: the nic-site. As a model example, a single transversion C24G in nic avoids DNA processing by TrwC. Using this simple model, our objective was to obtain a proof of principle that TrwC specificity can be changed. Several structures of DNA-TrwC complexes were used as reference to design a focused saturation mutagenesis library (NNK) randomizing amino acid Lys262, since its side chain seems to sterically hinder the recognition of the C24G nic mutation by wild-type TrwC. Using bacterial conjugation as an in vivo selection system, several TrwC variants were found that show changes in substrate specificity. These variants were also tested in a competitive assay to evaluate their conjugation efficiency.


Development of chronic venous disease.
Chronic venous disease is known to gradually worsen in the course of years. However, little clinical data is available. The patient group and methods: We used the set of our patients with completed clinical examination, duplex sonography and photoplethysmography and selected 160 patients examined at our office after 10 and more years. Females represented 79% in the group. The mean age was 54 years (range 18-82 years). Venous varices in lower limbs in the family were reported by 49% patients. Venous sclerotization had been undergone by 6.3% and venous surgery by 10.6% patients. The mean body mass index was 27. We used CEAP classification. The clinical class C1 included 50 patients, C2 included 81, C3 included 15 and C4 included 14 patients. Regurgitation in superficial veins was found in 43%. The mean venous return time after physical activity was 24.5 s. The last examination was performed after 13 years on average (range 10-28 years). Deterioration of the clinical condition and progression to a higher class were observed in 36% patients in class C1, in 23.5% patients in C2, in 13% patients in C3 and in 7% patients in C4. We did not demonstrate any statistically significant effect of the followed parameters on the progression of the disease. The progression rate of the disease in our patient group followed at the vascular office for 10 and more years is lower compared to population studies.


Endothelial dysfunction and blood pressure alterations in K+-channel transgenic mice.
K(+) channels are important regulators of arterial tone by providing membrane hyperpolarization and thus counteracting the activity of voltage-gated Ca(2+) channels in the smooth muscle and, thus, vasoconstriction. The endothelium and smooth muscle express a variety of different K(+) channels, such as Ca(2+)-activated K(+) channels (KCa), voltage-gated (KV), two-pore-domain (K2P), and inward rectifying (KIR) and KATP channels. Their contributions to the numerous mechanisms of endothelium-dependent and smooth muscle-dependent relaxation are closely related to their electrophysiological properties, activation mechanisms, and to differential expressions pattern within the vascular wall. Here, we summarize the cardiovascular phenotypes in murine models of genetic K(+)-channel deficiency and focus, in particular, on defective vasoregulation in mice deficient of endothelial Ca(2+)-activated K(+) channels, IK (KCa3.1) and SK (KCa2.3), and smooth muscle Ca(2+)-activated K(+) channels, BK (KCa.1.1). Genetic deficiency of endothelial IK and SK severely impairs the endothelium-derived hyperpolarization-mediated type of arterial dilation. Moreover, SK deficiency impairs NO-mediated dilator responses, thus indicating subtype-specific actions in endothelial function. Loss of IK and/or SK channels is associated with sizeable higher blood pressure. In contrast, genetic deficiency of smooth BK channels enhances arterial blood pressure which is linked to mainly a loss of spontaneous transient outward currents in the smooth muscle cells as well as renal and adrenal gland functions (hyperaldosteronism). In conclusion, genetic deficiency of vascular K(+) channels results in severe impairments of local and systemic blood pressure regulation. These alterations strengthen the perspective that vascular K(+) channels are potential pharmacologic targets for improvement of vasodilator functions in cardiovascular pathologies.


BACTEREMIC SHOCK--A MEDICAL EMERGENCY.
Bacteremic shock is second in frequency only to myocardial infarction as a cause of hypotension and death in hospitalized medical patients. The clinical course is marked by fever, usually with chills, and hypotension with a full pulse and warm extremities, followed by shock, often resistant to treatment. Anticipation of this complication in patients with certain predisposing diseases or factors facilitates early recognition of the symptoms and signs of bacteremic shock and prompt treatment. Early and effective treatment of the offending infection often prevents progression of hypotension to the stage of frank vascular collapse.


Cardiovascular responses to noradrenaline microinjection in the ventrolateral periaqueductal gray of unanesthetized rats.
The periaqueductal gray area (PAG) is a mesencephalic area involved in cardiovascular modulation. Noradrenaline (NA), a neurotransmitter involved in central blood pressure control, is present in the rat PAG. We report here on the cardiovascular effects caused by NA microinjection into the ventrolateral PAG (vlPAG) of unanesthetized rats and the peripheral mechanism involved in their mediation. NA microinjection in the vlPAG of unanesthetized rats evoked dose-related pressor and bradycardiac responses. No significant cardiovascular responses were observed in urethane-anesthetized rats. The pressor response was potentiated by pretreatment with the ganglion blocker pentolinium (5 or 10 mg/kg, intravenously). Pretreatment with the vasopressin antagonist dTyr(CH2)5 (Me)AVP (50 microg/kg, intravenously) blocked the pressor response evoked by the NA microinjection into the vlPAG. Additionally, circulating vasopressin content was found to be significantly increased after NA microinjection in the vlPAG. The results suggest that activation of noradrenergic synapses within the vlPAG modulates vasopressin release in unanesthetized rats.


Fabrication of Core Crosslinked Polymeric Micelles as Nanocarriers for Doxorubicin Delivery: Self-Assembly, In Situ Diselenide Metathesis and Redox-Responsive Drug Release.
Polymeric micelles (PMs) have been used to improve the poor aqueous solubility, slow absorption and non-selective biodistribution of chemotherapeutic agents (CAs), albeit, they suffer from disassembly and premature release of payloads in the bloodstream. To alleviate the thermodynamic instability of PMs, different core crosslinking approaches were employed. Herein, we synthesized the poly(ethylene oxide)-b-poly((2-aminoethyl)diselanyl)ethyl l-aspartamide)-b-polycaprolactone (mPEG-P(LA-DSeDEA)-PCL) copolymer which self-assembled into monodispersed nanoscale, 156.57 ± 4.42 nm, core crosslinked micelles (CCMs) through visible light-induced diselenide metathesis reaction between the pendant selenocystamine moieties. The CCMs demonstrated desirable doxorubicin (DOX)-loading content (7.31%) and encapsulation efficiency (42.73%). Both blank and DOX-loaded CCMs (DOX@CCMs) established appreciable colloidal stability in the presence of bovine serum albumin (BSA). The DOX@CCMs showed redox-responsive drug releasing behavior when treated with 5 and 10 mM reduced glutathione (GSH) and 0.1% H2O2. Unlike the DOX-loaded non-crosslinked micelles (DOX@NCMs) which exhibited initial burst release, DOX@CCMs demonstrated a sustained release profile in vitro where 71.7% of the encapsulated DOX was released within 72 h. In addition, the in vitro fluorescent microscope images and flow cytometry analysis confirmed the efficient cellular internalization of DOX@CCMs. The in vitro cytotoxicity test on HaCaT, MDCK, and HeLa cell lines reiterated the cytocompatibility (≥82% cell viability) of the mPEG-P(LA-DSeDEA)-PCL copolymer and DOX@CCMs selectively inhibit the viabilities of 48.85% of HeLa cells as compared to 15.75% of HaCaT and 7.85% of MDCK cells at a maximum dose of 10 µg/mL. Overall, all these appealing attributes make CCMs desirable as nanocarriers for the delivery and controlled release of DOX in tumor cells.


Imaging of the ovine corpus luteum microcirculation with contrast ultrasound.
Ultrasound contrast agents have been the subject of microvascular imaging research. The sheep corpus luteum (CL) is a microvascular tissue that provides a natural angiogenic and antiangiogenic process, which changes during the luteal phase of the estrous cycle of the ewe. It can also be controlled and monitored endocrinologically, providing a very attractive in vivo model for the study and development of microvascular measurement. The perfusion of the fully developed CL between days 8 and 12 of the estrous cycle was studied in six ewes. A Philips iU22 ultrasound scanner (Bothell, WA, USA) with the linear array probe L9-3 was used to capture contrast-enhanced images after an intravenous bolus injection of 2.4 mL SonoVue (Bracco S.P.A., Milan, Italy). Time-intensity curves of a region of interest inside the CL were formed from linearized image data. A lagged-normal model to simulate the compartmental kinetics of the microvascular flow was used to fit the data, and the wash-in time was measured. Good contrast enhancement was observed in the CLs of all animals and the wash-in time averaged at 5.5 s with 9% uncertainty. The regression coefficient was highly significant for all fits. These data correlated with stained endothelial area in the histology performed postmortem. Two ewes were injected with prostaglandin F2alpha to induce CL regression, which resulted in an increase of wash-in time after a few hours. The CL of the ewe is thus proposed as an ideal model for the study and development of microvascular measurements using contrast ultrasound. Our initial results demonstrate a highly reproducible model for the study of the microvascular hemodynamics in a range of tissues and organs.


Highly luminescent gold(I)-silver(I) and gold(I)-copper(I) chalcogenide clusters.
The reactions of [AuClL] with Ag(2)O, where L represents the heterofunctional ligands PPh(2)py and PPh(2)CH(2)CH(2)py, give the trigoldoxonium complexes [O(AuL)(3)]BF(4). Treatment of these compounds with thio- or selenourea affords the triply bridging sulfide or selenide derivatives [E(AuL)(3)]BF(4) (E=S, Se). These trinuclear species react with Ag(OTf) or [Cu(NCMe)(4)]PF(6) to give different results, depending on the phosphine and the metal. The reactions of [E(AuPPh(2)py)(3)]BF(4) with silver or copper salts give [E(AuPPh(2)py)(3)M](2+) (E=O, S, Se; M=Ag, Cu) clusters that are highly luminescent. The silver complexes consist of tetrahedral Au(3)Ag clusters further bonded to another unit through aurophilic interactions, whereas in the copper species two coordination isomers with different metallophilic interactions were found. The first is analogous to the silver complexes and in the second, two [S(AuPPh(2)py)(3)](+) units bridge two copper atoms through one pyridine group in each unit. The reactions of [E(AuPPh(2)CH(2)CH(2)py)(3)]BF(4) with silver and copper salts give complexes with [E(AuPPh(2)CH(2)CH(2)py)(3)M](2+) stoichiometry (E=O, S, Se; M=Ag, Cu) with the metal bonded to the three nitrogen atoms in the absence of AuM interactions. The luminescence of these clusters has been studied by varying the chalcogenide, the heterofunctional ligand, and the metal.


Dealing with Chronic Pain: Tips to Teach Undergraduate Health Sciences Students.
Chronic pain is a significant and costly problem all over the world that negatively impacts the quality of life of sufferers. There are clear discrepancies between the prevalence of chronic pain in society and the low priority assigned to educating future physicians about the complexities of pain. This condition also occurs in other undergraduate health science students, although research in this area has not been studied as much as in medical schools. Based on the International Association for the Study of Pain (IASP) Pain Curriculum Outline, a systematic search of the available literature, and the authors' own experiences, we highlight some relevant tips to educate health science trainees in the management of patients with chronic pain. These tips highlight current international recommendations for a comprehensive approach to this prevalent problem in society, which should be learnt during the university training of health professionals.


From physical dose constraints to equivalent uniform dose constraints in inverse radiotherapy planning.
Optimization algorithms in inverse radiotherapy planning need information about the desired dose distribution. Usually the planner defines physical dose constraints for each structure of the treatment plan, either in form of minimum and maximum doses or as dose-volume constraints. The concept of equivalent uniform dose (EUD) was designed to describe dose distributions with a higher clinical relevance. In this paper, we present a method to consider the EUD as an optimization constraint by using the method of projections onto convex sets (POCS). In each iteration of the optimization loop, for the actual dose distribution of an organ that violates an EUD constraint a new dose distribution is calculated that satisfies the EUD constraint, leading to voxel-based physical dose constraints. The new dose distribution is found by projecting the current one onto the convex set of all dose distributions fulfilling the EUD constraint. The algorithm is easy to integrate into existing inverse planning systems, and it allows the planner to choose between physical and EUD constraints separately for each structure. A clinical case of a head and neck tumor is optimized using three different sets of constraints: physical constraints for all structures, physical constraints for the target and EUD constraints for the organs at risk, and EUD constraints for all structures. The results show that the POCS method converges stable and given EUD constraints are reached closely.


Sporadic and epidemic community legionellosis: two faces of the same illness.
The present study compares the risk factors, presentation and outcome of community-acquired Legionella pneumophila pneumonia in 138 sporadic-case patients (1994-2004) and 113 outbreak-case patients (2002) treated in two hospitals in Catalonia (Spain) since urinary antigen assays were adopted. Univariate and multivariate analysis were performed to compare epidemiological and clinical features, blood chemistry values, radiological findings and outcome of sporadic and epidemic legionnaires' disease. Univariate analysis showed that male sex, chronic lung disease, HIV infection and immunosuppressive therapy prevailed in sporadic cases. Presentation with respiratory symptoms, confusion and blood chemistry alterations, such as hyponatraemia, aspartate aminotransferase and blood urea nitrogen elevation, and partial pressure of oxygen P(O)(2) <7.98 KPa (60 mmHg) were also more frequent in sporadic cases, while headache prevailed in outbreak cases. Sporadic cases had a greater delay in treatment, were more severe and had a worse outcome than epidemic cases. Multivariate analysis showed significant differences in sex, chronic lung disease, HIV infection and headache. The clinical and outcome differences between the two groups may be explained by the detection of milder forms of legionnaires' disease, the earlier treatment and the lower severity of underlying disease in the outbreak cases.


Thoracobiliary fistulas: literature review and a case report of fistula closure with omentum majus.
Thoracobiliary fistulas are pathological communications between the biliary tract and the bronchial tree (bronchobiliary fistulas) or the biliary tract and the pleural space (pleurobiliary fistulas). We have reviewed aetiology, pathogenesis, predilection formation points, the clinical picture, diagnostic possibilities, and therapeutic options for thoracobiliary fistulas. A patient with an iatrogenic bronchobiliary fistula which developed after radiofrequency ablation of a colorectal carcinoma metastasis of the liver is present. We also describe the closure of the bronchobiliary fistula with the greater omentum as a possible manner of fistula closure, which was not reported previously according to the knowledge of the authors. Newer papers report of successful non-surgical therapy, although the bulk of the literature advocates surgical therapy. Fistula closure with the greater omentum is a possible method of the thoracobiliary fistula treatment.


Immunohistochemical evaluation of the activation of hepatic progenitor cells and their niche in feline lymphocytic cholangitis.
Objectives The aim of the study was to compare the hepatic progenitor cell niche in healthy feline livers and the liver tissue of cats with lymphocytic cholangitis. Methods Immunohistochemical stainings for vimentin, laminin, beta (β)-catenin and Notch1 intracellular domain (NICD) were used on formalin-fixed liver biopsies from affected (n = 12) and unaffected cats (n = 2). Results All immunohistochemical markers used were expressed in more cells, or more intensely, in the liver tissue of cats with lymphocytic cholangitis than in the liver tissue of unaffected cats. Conclusions and relevance Enhanced expression of vimentin, laminin, cytoplasmic/nuclear β-catenin and NICD in liver biopsies from cats with lymphocytic cholangitis indicates that the hepatic progenitor cell (HPC) niche is remodelled and activated. HPCs might provide insights into new regenerative treatment options for lymphocytic cholangitis in cats in the future.


Morphological and Physiological Characteristics of Ebf2-EGFP-Expressing Cajal-Retzius Cells in Developing Mouse Neocortex.
Cajal-Retzius (CR) cells are one of the earliest populations of neurons in the cerebral cortex of rodents and primates, and they play a critical role in corticogenesis and cortical lamination during neocortical development. However, a comprehensive morphological and physiological profile of CR cells in the mouse neocortex has not yet been established. Here, we systematically investigated the dynamic development of CR cells in Tg(Ebf2-EGFP)58Gsat/Mmcd mice. The morphological complexity, membrane activities and presynaptic inputs of CR cells coordinately increase and reach a plateau at P5-P9 before regressing. Using 3D reconstruction, we delineated a parallel-stratification pattern of the axonal extension of CR cells. Furthermore, we found that the morphological structure and presynaptic inputs of CR cells were disturbed in Reelin-deficient mice. These findings confirm that CR cells undergo a transient maturation process in layer 1 before disappearing. Importantly, Reelin deficiency impairs the formation of synaptic connections onto CR cells. In conclusion, our results provide insights into the rapid maturation and axonal stratification of CR cells in layer 1. These findings suggest that both the electrophysiological activities and the morphology of CR cells provide vital guidance for the modulation of early circuits, in a Reelin-dependent manner.


Geographic variability in human papillomavirus vaccination among U.S. young women.
Little information is available on geographic disparity of human papillomavirus (HPV) vaccination among women aged 18-26 years in the U.S. Genital HPV is the most common sexually transmitted infection in the U.S. Persistent HPV infection with oncogenic types can cause cervical cancer. This study utilized data collected from the 2010 National Health Interview Survey (NHIS). It identified geographic variability and other factors contributing to the disparities in HPV vaccine series initiation in a nationally representative sample of women aged 18-26 years. The study utilized data collected from 1867 women who participated in the Cancer Control Module Supplement of the 2012 NHIS. A multivariable logistic regression model was used to assess characteristics associated with initiation of the HPV series. Analyses were performed in 2012. After adjusting for other characteristics, women living in the West and North Central/Midwest had 54% and 20% greater odds of initiating the HPV series, respectively, compared with those living in the Northeast. Other factors associated with HPV series initiation were younger age, Hispanic background, being single/never married, childlessness, a history of HPV, and current alcohol use. Factors correlated with failure to initiate the HPV series were: not having insurance, living below the 200% poverty level, not being a high school graduate, not currently using hormone-based birth control, most recent Pap >1 year ago, no regular provider, last clinic visit ≥12 months ago, and never having received the hepatitis B vaccine. Results demonstrate disparity in HPV vaccine uptake by region of residence in the U.S. among young women. Further research is needed to understand the factors contributing to this geographic disparity. Evaluation of vaccination policies and practices associated with higher coverage regions might help characterize effective methods to improve HPV vaccination among women aged 18-26 years.


Cyanotic congenital heart disease (CCHD) with symptomatic erythrocytosis.
Secondary erythrocytosis of cyanotic congenital heart disease (CCHD) is pathologically different from primary erythrocytosis of polycythemia vera (PV). An association between elevated hematocrit and thrombosis has been established in PV patients, and treatment guidelines recommend maintaining hematocrit <45%. Although an association between elevated hematocrit and thrombosis has not been established in CCHD and secondary erythrocytosis, the current clinical practice is to phlebotomize these patients to hematocrit <65%. We report a 21-year-old woman with CCHD who presented with symptomatic erythrocytosis with numbness and tingling with hemoglobin 25.2 g/dl and hematocrit 75.8%. Her symptoms resolved with IV hydration. Other factors, including dehydration and iron deficiency, may precipitate hyperviscosity symptoms. The treatment is volume replacement and low-dose iron therapy, not phlebotomy. Repeated phlebotomy causes iron deficiency with microcytic erythrocytes, which increases the whole blood viscosity and, therefore, can potentially accentuate rather than decrease the risk for a cerebrovascular accident.


Effect of plasma proteins on the sieving spectra of hemofilters.
qoffxture of neutral maltodextrins with a continuous molecular weight distribution from 340 to 120,000 daltons has been used alone or in the presence of plasma to determine solute rejection by four hemofilters and the effect of plasma on such rejection. High pressure liquid chromatographic analyses were utilized to establish concentration ratios of feed and filtrate solutions over a wide molecular weight range. At equal transmembrane velocities, the boundary layer-corrected rejection of each hemofilter was determined as a function of molecular weight. The presence of plasma increased rejection by the Amicon Diafilter 30, the Hospal RP-6, and the Gambro FH202 hemofilters , but the Fresenius D-6 was virtually unaffected.


A Mouse Model of Orthopedic Surgery to Study Postoperative Cognitive Dysfunction and Tissue Regeneration.
Surgery is commonly used to improve and maintain quality of life. Unfortunately, in vulnerable patients such as the elderly, complications may occur and significantly diminish the outcome. Indeed, after routine orthopedic surgery to repair a fracture, as many as 50% of elderly patients suffer from neurologic complications like delirium. Also, the capacity to heal and regenerate tissue after surgery decreases with age, and can impact the quality of fracture repair and even osseous integration of implants. Thus, a better understanding of mechanisms that drive these age-dependent changes could provide strategic targets to minimize risk for such complications and optimize outcomes. Here, we introduce a clinically relevant mouse model of tibial fracture. The postoperative changes in these mice mimic some of the cognitive impairments commonly observed after routine orthopedic surgery in humans. Briefly, an incision is performed in the right hind limb under strictly aseptic conditions. Muscles are disassociated, and a 0.38-mm stainless steel pin is inserted into the upper crest of the tibia, inside the intramedullary canal. Osteotomy is then performed, and the wound is stapled. We have used this model to investigate the effects of surgical trauma on postoperative neuroinflammation and behavioral changes. By applying this fracture model in combination with parabiosis, a surgical model in which 2 mice are anastomosed, we have studied cells and secreted factors that systemically rejuvenate organ function and tissue regeneration after injury. By following our step-by-step protocol, these models can be reproduced with high fidelity, and can be adapted to interrogate many biologic pathways that are altered by surgical trauma.


[Thromboprophylaxis in patients with coronary aneurysms caused by Kawasaki disease].
Patients with coronary artery aneurysms caused by Kawasaki disease are at increased risk of coronary thrombosis and ischemia. To prevent coronary thrombosis, long term thromboprophylaxis using anti-platelet drugs, such as aspirin, dipyridamole, ticlopidine, clopidogrel, and abciximab, with or without warfarin is recommended by official guidelines. In fact, aspirin or aspirin with warfarin are the most frequently administered regimen in these patients with coronary aneurysms. However, still there has been paucity of data and no randomized controlled study to determine the efficacy of these drugs. This short article describes the currently accepted practice of thromboprophylaxis in patients with coronary aneurysms caused by Kawasaki disease.


Functional comparison of the human epidermal growth factor receptor and telomerase reverse transcriptase promoters in canine tumor cells.
We previously showed that the promoter region of the human epidermal growth factor receptor (hEGFR) gene elicits high transduction efficiency, with transgene expression restricted to canine breast tumor cells. However, it was unclear whether this promoter induces tumor cell-specific transgene expression in canine urothelial carcinoma cells. Furthermore, compared with studies in human cancer cells, the utility of the telomerase reverse transcriptase (TERT) gene promoter for therapeutic transgene expression in canine cancer cells has not been evaluated thus far. Here, we compared the activity of these promoters in canine mammary tumor and urothelial carcinoma cells. Our results showed that compared with the TERT promoter, the hEGFR promoter was more useful as a tumor-specific promoter to induce efficient transgene expression in canine tumor cells.


Real-time multiplexed digital cavity-enhanced spectroscopy.
Cavity-enhanced spectroscopy is a sensitive optical absorption technique but one where the practical applications have been limited to studying small wavelength ranges. This Letter shows that wideband operation can be achieved by combining techniques usually reserved for the communications community with that of cavity-enhanced spectroscopy, producing a multiplexed real-time cavity-enhanced spectrometer. We use multiple collinear laser sources operating asynchronously and simultaneously while being detected on a single photodetector. This is synonymous with radio frequency (RF) cellular systems in which signals are detected on a single antenna but decoded uniquely. Here, we demonstrate results with spectra of methyl salicylate and show parts-per-billion per root hertz sensitivity measured in real-time.


Monoclonal B-cell lymphocytosis in blood donors in Turkey.
Monoclonal B-cell lymphocytosis (MBL) is a precursor state of chronic lymphocytic leukemia (CLL) with peripheral lymphocytosis below 5 × 109/l. The diagnostic criteria exclude the presence of lymphadenopathy, organomegaly, infections, autoimmune diseases or any sign of a lymphoproliferative disorder. This prospective study was designed in order to evaluate the frequency of MBL in blood donors in Turkey. The diagnosis of MBL was identified by flow cytometry method based on the International Familial CLL Consortium Report. A total of 999 volunteers [median age 34 (18-78) years; male/female: 705/294] were included in the study. Monoclonal B-cell lymphocytosis was demonstrated in 18 cases (1.8%). A total of 16 cases (1.6%) was evaluated as CLL-like MBL, while 2 (0.2%) had a non-CLL-like phenotype. The subjects were divided into three groups according to age, as <40 years, 40-60 years and >60 years. The prevalence of MBL was 1.1% below 40 years, 0.6% between 40 and 60 years and 0.1% in cases over 60 years, without statistical significance (p > 0.05). The sensitivity of the flow cytometry method is essential and may be responsible for the variations in the prevalence of MBL in different populations which can also be attributed to study design, higher detection rates in the elderly and families with genetic predisposition to CLL. Large population-based studies and standardized laboratory methods are needed to determine the potential risk factors of progression to CLL, including molecular markers and genetic profile.


Prevention of intraoral trauma in sports.
Dental, oral, facial, and cranial injuries can be reduced by the use of mouthguards and faceguards. Disadvantages of mouthguard use are based mostly on lack of information. There is a growing endorsement for the use of mouthguards and faceguards, presenting the dental profession with a major opportunity to improve the oral health of athletes.


Meta-analysis of counseling and psychotherapy outcome studies in Taiwan.
This study applied the meta-analysis method to investigate the effectiveness of counseling and psychotherapy. It began with a systematic search of the literature through computer search and previous narrative reviews to locate counseling and psychotherapy outcome studies conducted in Taiwan between January 1971 and August 2000. Salient characteristics of each study were recorded systematically. These study characteristics included type of therapy, type of target problem, therapist experience, and type of outcome measure, among others. In total, 257 studies, which yielded 302 effect sizes, were examined, in which clients who received psychotherapy or counseling were compared with controls. Results demonstrated that the overall mean effect of counseling and psychotherapy was positive and significant. Further categorical model testing indicated that most coded study characteristics were significantly related to effect sizes.


Formation of stable uranium(VI) colloidal nanoparticles in conditions relevant to radioactive waste disposal.
The favored pathway for disposal of higher activity radioactive wastes is via deep geological disposal. Many geological disposal facility designs include cement in their engineering design. Over the long term, interaction of groundwater with the cement and waste will form a plume of a hyperalkaline leachate (pH 10-13), and the behavior of radionuclides needs to be constrained under these extreme conditions to minimize the environmental hazard from the wastes. For uranium, a key component of many radioactive wastes, thermodynamic modeling predicts that, at high pH, U(VI) solubility will be very low (nM or lower) and controlled by equilibrium with solid phase alkali and alkaline-earth uranates. However, the formation of U(VI) colloids could potentially enhance the mobility of U(VI) under these conditions, and characterizing the potential for formation and medium-term stability of U(VI) colloids is important in underpinning our understanding of U behavior in waste disposal. Reflecting this, we applied conventional geochemical and microscopy techniques combined with synchrotron based in situ and ex situ X-ray techniques (small-angle X-ray scattering and X-ray adsorption spectroscopy (XAS)) to characterize colloidal U(VI) nanoparticles in a synthetic cement leachate (pH > 13) containing 4.2-252 μM U(VI). The results show that in cement leachates with 42 μM U(VI), colloids formed within hours and remained stable for several years. The colloids consisted of 1.5-1.8 nm nanoparticles with a proportion forming 20-60 nm aggregates. Using XAS and electron microscopy, we were able to determine that the colloidal nanoparticles had a clarkeite (sodium-uranate)-type crystallographic structure. The presented results have clear and hitherto unrecognized implications for the mobility of U(VI) in cementitious environments, in particular those associated with the geological disposal of nuclear waste.


Social-cognitive predictors of fruit and vegetable intake in children.
Social-cognitive theory (SCT) was used to explain the fruit and vegetable intake of 1,398 3rd graders. SCT variables assessed included self-efficacy, outcome expectations, preferences, social norms, asking skills, and knowledge. Fruit and vegetable intake was assessed with 7-day records. Bivariate correlations with fruit and vegetable intake ranged from .17 for asking skills to .29 for fruit and vegetable preferences. In analyses controlling for school-level clustering, only preferences and positive outcome expectations remained significantly associated with fruit and vegetable intake, accounting for approximately 10%-11% of the variance. Limitations in the conceptualization, scope, and measurement of the variables assessed may have contributed to the weak associations observed. Models incorporating factors other than individual-level social-cognitive variables may be required to more fully explain children's dietary behavior.


Trends in the treatment of risk factors for stroke in a Czech stroke unit.
The goal of this study is to evaluate therapeutic trends for several diseases that represent risk factors for stroke. The relative frequency of therapy with compounds that influence the risk factors for stroke was monitored in a group of 3,290 patients who were hospitalised in the Stroke Unit at the University Hospital in Hradec Kralove between 2005 and 2012. For most drugs monitored, the reasons for the significant decrease or increase in use were causes other than the reduction of stroke risk. Despite this finding, the majority of statistically significant changes had, according to review of comparative studies, a positive effect on prevention of stroke. Motivation to change treatment of stroke risk factors, such as hypertension, diabetes mellitus and hypercholesterolemia, was mainly aimed at sufficient disease management with a minimum of adverse effects. On the other hand, optimization of stroke recurrence and economic factors were motivations to treatment changes in prevention with antiplatelets. Antidiabetics were associated with an increase in metformin use and reduction in insulin use. For antihypertensives, the most significant reduction was associated with the use of diuretics, although calcium channel blockers and beta-blockers are also less used. Additionally, the use of the ACE inhibitor ramipril increased.


Theoretical analysis of defect-mediated turbulence in a catalytic surface reaction.
We present a statistical analysis of defect-mediated turbulence in a kinetic model of catalytic CO oxidation on Pt(110). A probabilistic description based on the gain and loss rates of defects is derived. For low values of the CO partial pressure the statistics of topological defects agree with earlier results for the complex Ginzburg-Landau equation. For high values of the CO partial pressure, we observe an additional autocatalytic reproduction of defects that results in a linear dependence of the defect creation rate on the number of defects in the system. The role of correlations between defects of opposite topological charge was found to be weaker than in the experimental system.


Anti-doping testing at the 2008 European football championship.
Big sports events like the 2008 European Football Championship are a challenge for anti-doping activities, particularly when the sports event is hosted by two different countries and there are two laboratories accredited by the World Anti-Doping Agency. This challenges the logistics of sample collection as well as the chemical analyses, which must be carried out timeously. The following paper discusses the handling of whereabouts information for each athlete and the therapeutic use exemption system, experiences in sample collection and transportation of blood and urine samples, and the results of the chemical analysis in two different accredited laboratories. An overview of the analytical results of blood profiling and growth hormone testing in comparison with the distribution of the normal population is also presented.


Glycerol production by microbial fermentation: a review.
Microbial production of glycerol has been known for 150 years, and glycerol was produced commercially during World War I. Glycerol production by microbial synthesis subsequently declined since it was unable to compete with chemical synthesis from petrochemical feedstocks due to the low glycerol yields and the difficulty with extraction and purification of glycerol from broth. As the cost of propylene has increased and its availability has decreased especially in developing countries and as glycerol has become an attractive feedstock for production of various chemicals, glycerol production by fermentation has become more attractive as an alternative route. Substantial overproduction of glycerol by yeast from monosaccharides can be obtained by: (1) forming a complex between acetaldehyde and bisulfite ions thereby retarding ethanol production and restoring the redox balance through glycerol synthesis; (2) growing yeast cultures at pH values near 7 or above; or (3) using osmotolerant yeasts. In recent years, significant improvements have been made in the glycerol production using osmotolerant yeasts on a commercial scale in China. The most outstanding achievements include: (1) isolation of novel osmotolerant yeast strains producing up to 130 g/L glycerol with yields up to 63% and the productivities up to 32 g/(L day); (2) glycerol yields, productivities and concentrations in broth up to 58%, 30 g/(L day) and 110-120 g/L, respectively, in an optimized aerobic fermentation process have been attained on a commercial scale; and (3) a carrier distillation technique with a glycerol distillation efficiency greater than 90% has been developed. As glycerol metabolism has become better understood in yeasts, opportunities will arise to construct novel glycerol overproducing microorganisms by metabolic engineering.


Effects of intranasally dosed posaconazole on fungal load and biomarkers in Aspergillus fumigatus infected immunocompromised mice.
Although anti-fungal triazoles are dosed orally or systemically for Aspergillus fumigatus infection, systemic adverse events and limited exposure of the lung cavity would make a topical treatment for the lung an attractive option. In this study, we examined the effects of intranasally dosed posaconazole on survival rates and biomarkers in A. fumigatus (itraconazole susceptible: ATCC13073 [Af]; or resistant: NCPF7100 [AfR]) infected, temporarily neutropenic A/J mice. Once daily treatment produced a dose-dependent improvement of survival of Af-infected mice (ED50 : 0.019 mg/mouse [approx. 0.755 mg/kg, in]), similar to its potency (ED50 : 0.775 mg/kg, po) after once daily oral dosing. For AfR infection, either intranasal or oral posaconazole was largely ineffective on survival, although the highest dose of intranasal treatment (0.35 mg/mouse) achieved 75% survival rate. Early intervention (treated on days 0, 1, 2 and 3 postinfection) and late intervention (treated on days 1, 2 and 3) with intranasal posaconazole (0.014-0.35 mg/mouse) demonstrated potent inhibition of lung fungal load and galactomannan levels in both bronchoalveolar lavage fluid (BALF) and serum as well as inflammatory cells, IFN-γ, IL-17 and malondialdehyde (MDA) in BALF. Thus, posaconazole when dosed intranasally once daily showed an improvement of survival equivalent to or better than oral treatment, and produced potent inhibition of fungal load and biomarkers.


Specific Patterns of Postoperative Temperature Elevations Predict Blood Infection in Pediatric Burn Patients.
Using readily available temperature data, we seek to propose a scoring criteria that can facilitate accurate and immediate prediction of blood infection. The standard in diagnosing blood infection is a positive blood culture result that may take up to 3 days to process, requiring providers to make a prediction about which febrile patient is actually bacteremic. This prediction is difficult in burned children as systemic inflammation can cause fever in the absence of infection. An ability to make this prediction more accurate using readily available information would be useful. A retrospective chart review was performed for 28 pediatric patients, with a burn size 20% or greater, admitted to the burn unit between 2010 and 2014. All children had blood cultures drawn. They were divided into either infection (positive blood cultures) or control (negative blood cultures) groups. Median temperature and mean number of temperature elevations were compared between the two groups. We evaluated the predictive accuracy of using temperature elevation, pattern, and timing to predict blood infection. A significant difference was seen in the mean number of temperature elevations above 39°C. This was significant for each time stage, especially in the 0- to 24-hour post-surgery period. We found the most predictive accuracy in the 0- to 12-, 12- to 38-, and 12- to 48-hour time periods. We found a strong association between mean number of fever spikes above 39°C and blood infection, especially 12 to 24 hours after surgery. This readily available data can be useful to clinicians as they access children with burns.


Peptide-induced formation of a tethered lipid bilayer membrane on mesoporous silica.
Tethered bilayer lipid membranes (tBLMs) on solid supports have substantial advantages as models of artificial cell membranes for such biomedical applications as drug delivery and biosensing. Compared with untethered lipid membranes, tBLMs have more space between substrate and the bilayer and greater stability. The purpose of this work was to use these properties to fabricate and characterize a zwitterionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine lipid tBLM containing 2 mol% 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-maleimide(poly(ethylene glycol))-2000 (DSPE-PEG2000-NHS) lipid tethers on a 3-aminopropyltrimethoxysilane-modified mesoporous silica substrate. A quartz crystal microbalance with dissipation monitoring was used to monitor the process of vesicle adsorption and tBLM self-assembly, and atomic force microscopy was performed to characterize the structural properties of the tBLM obtained. Whereas tether-containing lipid vesicles ruptured neither spontaneously nor as a result of osmotic shock, introduction of an amphipathic α-helical (AH) peptide induced vesicle rupture and subsequent tBLM formation. Taken together, our findings suggest that the AH peptide is an efficient means of rupturing vesicles of both simple and complex composition, and is, therefore, useful for formation of tBLMs on solid and mesoporous materials for applications in biotechnology.


Conformational transition of a hairpin structure to G-quadruplex within the WNT1 gene promoter.
The role of G-quadruplexes (G4s) in biological systems has been widely studied. It is found that they have an important function in gene transcription and regulation. In this work, we have identified two topologies of hairpin and G4 structures formed by a native G-rich sequence (WT22: 5'-GGGCCACCGGGCAGGGGGCGGG-3') from the WNT1 promoter region using nuclear magnetic resonance (NMR) spectroscopy. With the help of site-specific isotope labeling, the topologies of these two structures are unambiguously characterized. Circular dichroism and NMR results are analyzed to determine the kinetics associated with the potassium ion-induced hairpin-to-G4 transition, which is very slow-on the time scale of 4800 s-compared to the previously reported folding kinetics of G4 formation. In addition, the free energies of the unfolding of these two structures are obtained using differential scanning calorimetry. Combining the kinetic and thermodynamic data, we have established the free energy landscape of this two-state folding system. Considering that similar conformational change may exist in other native G-rich sequences, this work highlights an important hairpin to G4 conformational transition which can be used in manipulation of gene regulation or ligand modulation in vivo.


Risk factors for cardiovascular complications following total joint replacement surgery.
To determine risk factors for cardiac complications following total joint replacement (TJR) surgery. We performed a case-control study of patients who had undergone a primary or revision total knee or total hip replacement surgery. Cases consisted of those who received a TJR and experienced a cardiac complication during the surgical admission period (myocardial infarction [MI], congestive heart failure [CHF], unstable angina, arrhythmia, symptomatic hypotension, or pulmonary embolus). Controls consisted of those who received a TJR and did not experience a cardiac complication during the surgical admission period. Controls were matched to the cases for age at surgery, year of surgery, and surgeon. Case and control status and identification of potential risk factors were ascertained by review of medical records. Conditional logistic regression analysis was used to identify independent predictors of cardiac complications. The sample included 209 cases and 209 controls. Factors associated with a higher risk of cardiac complications included a history of arrhythmia (adjusted odds ratio [OR] 2.6 [95% confidence interval (95% CI) 1.5-4.3]), a history of coronary artery disease, MI, CHF, or valvular heart disease (OR 1.6 [95% CI 0.9-2.6]), revision surgery (OR 2.2 [95% CI 1.2-3.9]), and bilateral surgery (adjusted OR 3.5 [95% CI 1.6-8.0]). Even though controls were matched for age (within age brackets), age was still associated with a higher risk of cardiac complications (OR 1.7 [95% CI 0.9-3.4]). This case-control study identified 2 new risk factors for cardiac complications following TJR: bilateral and revision surgery. The study also confirmed previously documented risk factors, including older age at surgery and a history of arrhythmia and of other cardiac problems. These findings should help clinicians anticipate and prevent cardiac complications following TJR surgery.


Incidence of Nd:YAG capsulotomy after implantation of AcrySof multifocal and monofocal intraocular lenses: a case controlled study.
To compare the frequency of posterior capsulotomies in patients receiving a multifocal or monofocal intraocular lens (IOL) of a similar design following cataract extraction. Four hundred seventeen eyes underwent cataract extraction and IOL implantation; 275 eyes received the AcrySof SN6OWF (Alcon Laboratories Inc) one-piece monofocal lens (monofocal group) and 142 eyes received the RESTOR multifocal lens (SN60D3 or SA60D3, Alcon Laboratories Inc) (multifocal group). Surgery was performed by two surgeons at one site. Primary outcome measures were incidence, time of onset, and preoperative corrected distance visual acuity (CDVA) for those patients receiving posterior capsulotomies. After average 22-month postoperative follow-up (range: 2 to 41 months), 22 (15.49%) eyes in the multifocal group underwent posterior capsulotomies compared with 16 (5.82%) eyes in the monofocal group (P = .0014). The main indication for Nd:YAG laser capsulotomy in the multifocal group was complaint of poor quality of vision rather than decreased CDVA. The multifocal group underwent capsulotomies after a mean of 8.8 months (range: 1.7 to 29.2 months), whereas the monofocal group required capsulotomies after a mean of 10.4 months (range: 0.8 to 28.6 months) (P = .559). Mean logMAR CDVA before capsulotomy was 0.113 (range: 0 to 0.6) for the multifocal group and 0.244 (range: 0 to 0.48) for the monofocal group (P = .073). Use of the RESTOR multifocal IOL in clinical practice may result in more frequent Nd:YAG laser capsulotomies. Reasons for this may include increased visual demands of patients receiving presbyopic-correcting IOLs or complex visual phenomena associated with the interaction of multifocal optics and posterior capsule opacification.


Integration of Random Forest Classifiers and Deep Convolutional Neural Networks for Classification and Biomolecular Modeling of Cancer Driver Mutations.
Development of machine learning solutions for prediction of functional and clinical significance of cancer driver genes and mutations are paramount in modern biomedical research and have gained a significant momentum in a recent decade. In this work, we integrate different machine learning approaches, including tree based methods, random forest and gradient boosted tree (GBT) classifiers along with deep convolutional neural networks (CNN) for prediction of cancer driver mutations in the genomic datasets. The feasibility of CNN in using raw nucleotide sequences for classification of cancer driver mutations was initially explored by employing label encoding, one hot encoding, and embedding to preprocess the DNA information. These classifiers were benchmarked against their tree-based alternatives in order to evaluate the performance on a relative scale. We then integrated DNA-based scores generated by CNN with various categories of conservational, evolutionary and functional features into a generalized random forest classifier. The results of this study have demonstrated that CNN can learn high level features from genomic information that are complementary to the ensemble-based predictors often employed for classification of cancer mutations. By combining deep learning-generated score with only two main ensemble-based functional features, we can achieve a superior performance of various machine learning classifiers. Our findings have also suggested that synergy of nucleotide-based deep learning scores and integrated metrics derived from protein sequence conservation scores can allow for robust classification of cancer driver mutations with a limited number of highly informative features. Machine learning predictions are leveraged in molecular simulations, protein stability, and network-based analysis of cancer mutations in the protein kinase genes to obtain insights about molecular signatures of driver mutations and enhance the interpretability of cancer-specific classification models.


H3K4me3 interactions with TAF3 regulate preinitiation complex assembly and selective gene activation.
Histone modifications regulate chromatin-dependent processes, yet the mechanisms by which they contribute to specific outcomes remain unclear. H3K4me3 is a prominent histone mark that is associated with active genes and promotes transcription through interactions with effector proteins that include initiation factor TFIID. We demonstrate that H3K4me3-TAF3 interactions direct global TFIID recruitment to active genes, some of which are p53 targets. Further analyses show that (1) H3K4me3 enhances p53-dependent transcription by stimulating preinitiation complex (PIC) formation; (2) H3K4me3, through TAF3 interactions, can act either independently or cooperatively with the TATA box to direct PIC formation and transcription; and (3) H3K4me3-TAF3/TFIID interactions regulate gene-selective functions of p53 in response to genotoxic stress. Our findings indicate a mechanism by which H3K4me3 directs PIC assembly for the rapid induction of specific p53 target genes.


Addressing Food Insecurity to Optimize Nutritional Status.
Chronic health conditions related to diet are linked with increased risk for COVID-19 infection, complications, and mortality. Adherence to a healthy diet pattern can be protective, but a major barrier to healthy eating is the high cost of healthy foods. Access to healthy foods is especially limited in households that experience food insecurity, not having enough food or resources to get food. Individuals who live in these households are also at increased risk for a number of health conditions. Addressing food insecurity within lifestyle medicine practice is needed to achieve optimal nutrition status. Emerging food as medicine and other food access programs are promising but coverage of such programs is lacking through healthcare insurers. Medicaid waivers are a potential solution and have been utilized in a handful of states.


MANAGEMENT OF INFLAMMATORY APPENDICEAL MASS IN ZEWDITU MEMORIAL HOSPITAL, ADDIS ABABA, ETHIOPIA.
Appendiceal mass is one of the complications of acute appendicitis. The management of patients with appendiceal mass is controversial and different treatment options have been suggested. The objective of this study was to assess the results of conservative management of patients with appendiceal mass followed by interval appendicecomy. The study was a retrospective analysis of 73 medical records of patients with appendiceal mass who were managed conservatively between March 2007 and February 2014. Fifty patients were males and 23 patients were females making the male to female ratio of 2.2:1. The mean age was 29.6 ± 6.3 years (range 12-68 years). The maximum incidence was in the 3rd decade. Forty one (55.8%) of the patients presented one week or more after the onset of their illness. Abdominal pain, right lower quadrant (RLQ) direct and rebound tenderness were observed in all patients. Mass was detected in the RLQ in 84.9% of the patients. Sixty five patients (89%) responded to conservative treatment and these patients were discharged after a mean hospital stay of 6.5 1.5 days (range 3-12 days). Interval appendicectomy was done for 58 patients 8-16 weeks after successful conservative management. The mean hospital stay after interval appendicectomy was 3.5 ± 0.5 days with a range of 2-5 days. One patient (1.7%) had a wound infection. There were no deaths. Initial non-operative management of appendiceal mass was successful in most cases and the complication rate after interval appendicecomy seems lower than with early operative treatment.


Role of ST-Segment Resolution Alone and in Combination With TIMI Flow After Primary Percutaneous Coronary Intervention for ST-Segment-Elevation Myocardial Infarction.
Background To evaluate the role of ST-segment resolution (STR) alone and in combination with Thrombolysis in Myocardial Infarction (TIMI) flow in reperfusion evaluation after primary percutaneous coronary intervention (PPCI) for ST-segment-elevation myocardial infarction by investigating the long-term prognostic impact. Methods and Results From January 2013 through September 2014, we studied 5966 patients with ST-segment-elevation myocardial infarction enrolled in the CAMI (China Acute Myocardial Infarction) registry with available data of STR evaluated at 120 minutes after PPCI. Successful STR included STR ≥50% and complete STR (ST-segment back to the equipotential line). After PPCI, the TIMI flow was assessed. The primary outcome was 2-year all-cause mortality. STR < 50%, STR ≥50%, and complete STR occurred in 20.6%, 64.3%, and 15.1% of patients, respectively. By multivariable analysis, STR ≥50% (5.6%; adjusted hazard ratio [HR], 0.45 [95% CI, 0.36-0.56]) and complete STR (5.1%; adjusted HR, 0.48 [95% CI, 0.34-0.67]) were significantly associated with lower 2-year mortality than STR <50% (11.7%). Successful STR was an independent predictor of 2-year mortality across the spectrum of clinical variables. After combining TIMI flow with STR, different 2-year mortality was observed in subgroups, with the lowest in successful STR and TIMI 3 flow, intermediate when either of these measures was reduced, and highest when both were abnormal. Conclusions Post-PPCI STR is a robust long-term prognosticator for ST-segment-elevation myocardial infarction, whereas the integrated analysis of STR plus TIMI flow yields incremental prognostic information beyond either measure alone, supporting it as a convenient and reliable surrogate end point for defining successful PPCI. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01874691.


Vibrational spectra of C60.C8H8 and C70.C8H8 in the rotor-stator and polymer phases.
C(60).C(8)H(8) and C(70).C(8)H(8) are prototypes of rotor-stator cocrystals. We present infrared and Raman spectra of these materials and show how the rotor-stator nature is reflected in their vibrational properties. We measured the vibrational spectra of the polymer phases poly(C(60)C(8)H(8)) and poly(C(70)C(8)H(8)) resulting from a solid-state reaction occurring on heating. On the basis of the spectra, we propose a connection pattern for the fullerene in poly(C(60)C(8)H(8)), where the symmetry of the C(60) molecule is D(2h). On illuminating the C(60).C(8)H(8) cocrystal with green or blue light, a photochemical reaction was observed leading to a product similar to that of the thermal polymerization.


Cerebrospinal setariosis with Setaria marshalli and Setaria digitata infection in cattle.
Setaria digitata and S. marshalli larvae were observed in the cerebrospinal cavity of 2 paralyzed cattle in Taiwan. The 2 affected cattle showed quadriplegia and lumbar paralysis, respectively. At necropsy, which was performed 7 days after the 7-month-old cattle became quadriplegic, three and nineteen S. marshalli larvae as well as two female adult worms were found in the cranial cavity, spinal cavity and peritoneal cavity of the cattle, respectively. Necropsy on the other 8-month-old cattle was also performed 3 days after it showed lumbar paralysis, and ten S. digitata larvae were found in the spinal cavity. In both cattle, many mononuclear inflammatory cells mixed with a few eosinophils were seen accumulated in the connective tissue around the root of the spinal nerves. Infiltration of eosinophils and mononuclear inflammatory cells into the epidura and arachnoidea of the brain were also observed. The major inflammatory cell was lymphocytes, but neutrophils and eosinophils were also present. The number of cells in the cerebrospinal fluid collected initially from the two affected cattle were 105/0.01 ml and 143/ 0.01 ml, respectively. This is the first report of cerebrospinal setariosis in cattle associated with S. marshalli.


[Regional transarterial infusion of autologous lymphokine-activated killer (LAK) cells for advanced renal cell carcinoma and its preliminary clinical result].
We herein report the preliminary but appreciable results of regional transarterial infusion of 2 gravity subtypes of autologous lymphokine-activated killer (LAK) cells into the metastatic sites in combination with systemic recombinant interleukin-2 (rIL-2) administration in 3 patients with advanced renal cell carcinoma. Leukapheresis was performed once a week and peripheral blood lymphocytes were separated into 2 different subtypes by Percoll gradient centrifugation. These lymphocytes were incubated with rIL-2 for a few days to induce LAK cells. LAK cells were transferred to the metastatic lesions through cannula twice a week. A large iliac bone metastasis disappeared 3 months after the initial LAK cell therapy via a superior gluteal artery. A case of complete disappearance of psoas muscle and para-aortic lymphnode metastasis as well as partial regression of a lumbar bone metastasis was seen after lumbar arterial infusion treatment. Another case with brain metastasis showed a rapid exacerbation of brain edema after one week's LAK therapy. Our treatment modality seems to be worthwhile and promising for treatment of the advanced renal cell carcinoma.


Subacute proximal leg weakness after a minor traffic accident in a patient treated with anticoagulants.
One day after a minor accident, an 85-year-old man developed headache and proximal left leg weakness. He was on warfarin due to atrial fibrillation. On hospital admission, a right posterior parasagittal subdural haematoma that was visualised on CT was considered as cause of all symptoms. Although no surgical intervention was performed he stayed for 2 weeks in a neurosurgical ward. Clinical deterioration occurred within the first days as he was not able to stand on his left leg or rise up from the sitting position. Headache had ceased, but the patient reported low abdominal pain. This condition remained stable for over 2 months although haematoma size decreased significantly. He was then examined for the first time by a neurologist who documented typical clinical features of femoral nerve palsy. Pelvic CT established the diagnosis of traumatic iliacus- and iliopsoas-muscle haematoma under anticoagulants as cause of subacute femoral mononeuropathy.


[The pirymethamine influence on hexosoaminidase gene expression in synovial cell culture--preliminary report].
Inflammation process is leading to increasing of synovial fluid and value of its pressure. Moreover, the impairment of vascular flow within synovial membrane and increased permeability of blood vessels were described. The activity of lysosomal enzymes, such as N-acetyl-beta-glucosaminidase (HEX), was increased in patients with rheumatoid arthritis in comparison to health synovial fluid. It is supposed, that HEX takes part in joint destruction. The using of HEX inhibitors in synovial cell culture and evaluation of HEX mRNA expression before and after the adding of inhibitor may contribute in showing the new ways of understanding pathogenetic pathways of motion organ disorders. THE AIM of the study was to evaluate the expression of HEXA and HEXB genes in the synovial cell culture derived from human synovial inflammatory fluid obtained from patients suffered from rheumatoid arthritis. The inflamed synovial fluid was taken from patients suffered from rheumatoid arthritis. The following solutions of potential inhibitor--pyrimethamine were used: 20 microg/ml, 10 microg/ml, 3 microg/ml and 1.5 microg/ml. Two separate control groups were established: control group 1 where only 0.6% of ethanol was added to the synovial cell culture; control group 2 where only 0.5% DMSO was added to the synovial cell culture. The relative quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) was carried out. RESULTS. The difference in HEXA and HEXB expression was observed in synoviocytes obtained in synovial cell culture. Five time higher relative HEXA expression was determined after applying 3 microg/ml of pirymethamine compared with the control 1. The highest concentration of pirymethamine (10 and 20 microg/ml) caused the least elevation of HEXA expression. The slight decreased of HEXB expression was observed under the concentration of pirymethamine: 1.3 and 3 microg/ml. CONCLUSIONS. Pyrimethamine contributes to regulating the HEX gene expression from synovial cells. The change in gene expression level is dependent on the concentration of the pirymethamine. Our preliminary data don't let us establish the concentration of pyrimethamine that may significantly inhibit HEXA and HEXB expression. Further study may be conducted to put new insight into the pathogenesis of joint destruction in the course of rheumatoid arthritis.


Preclinical stem cell therapy in Chagas Disease: Perspectives for future research.
Chagas cardiomyopathy still remains a challenging problem that is responsible for high morbidity and mortality in Central and Latin America. Chagas disease disrupts blood microcirculation via various autoimmune mechanisms, causing loss of cardiomyocytes and severe impairment of heart function. Different cell types and delivery approaches in Chagas Disease have been studied in both preclinical models and clinical trials. The main objective of this article is to clarify the reasons why the benefits that have been seen with cell therapy in preclinical models fail to translate to the clinical setting. This can be explained by crucial differences between the cellular types and pathophysiological mechanisms of the disease, as well as the differences between human patients and animal models. We discuss examples that demonstrate how the results from preclinical trials might have overestimated the efficacy of myocardial regeneration therapies. Future research should focus, not only on studying the best cell type to use but, very importantly, understanding the levels of safety and cellular interaction that can elicit efficient therapeutic effects in human tissue. Addressing the challenges associated with future research may ensure the success of stem cell therapy in improving preclinical models and the treatment of Chagas disease.


Contact lens-related infectious keratitis.
Infectious keratitis is the most serious complication of contact lens use. Virtually all contact lens wearers are at risk. Initial therapy consists of frequent broad-spectrum fortified antibiotic drops after appropriate laboratory workup. Pseudomonas and Acanthamoeba species are the most important causes of contact lens-associated ulcers. Acanthamoeba keratitis produces significant ocular morbidity, and treatment is not always effective. Recent studies have provided new insights regarding the incidence, risk factors, and pathogenesis of contact lens-related infectious keratitis. Extended-wear soft contact lens wearers are at greatest risk. With our present understanding of the pathogenesis and risk factors of contact lens-related infectious keratitis, daily-wear schedules are strongly advised. Even under the best of lens care conditions, infectious keratitis may still occur. It is therefore imperative that patients be informed to remove their lenses and seek medical evaluation if any discomfort develops.


Atypical posttraumatic dystonia treated successfully by botulinum toxin injection.
This study presents the case of a 39-yr-old woman who had atypical involuntary dystonic movements of the shoulder and back. Ten months earlier, she was involved in a motor vehicle collision. Involuntary movements developed abruptly 3 wks before her first visit to the clinic. Her involuntary movements had some atypical features, such as continuous, bizarre, and rhythmic or semirhythmic characteristics, and showed mixed symmetric and asymmetric patterns. She was treated successfully with electromyography-guided botulinum toxin type A injection. Involuntary dystonic movements may be due to posttraumatic dystonia, a relatively uncommon diagnosis. Atypical posttraumatic dystonia may be managed effectively with botulinum toxin type A injections.


Bioavailability of tyrosine kinase inhibitors: an added component of assessment.
The growing prominence of tyrosine kinase inhibitors (TKIs) as treatment for malignancies prompts oncology nurses to expand the scope of their patient assessment. Because TKIs as oral agents have a different bioavailability than parenteral agents, factors that alter drug absorption and metabolism can have a measurable effect on the amount of active, available drug when TKIs are prescribed. In relation to TKIs as cancer therapies and intended dosing, this article reviews three drug absorption and metabolism factors: changes in stomach pH, as well as P-glycoprotein and cytochrome P450 interactions.


A New Consensus Model Based on Trust Interactive Weights for Intuitionistic Group Decision Making in Social Networks.
A promising feature for group decision making (GDM) lies in the study of the interaction between individuals. In conventional GDM research, experts are independent. This is reflected in the setting of preferences and weights. Nevertheless, each expert's role is played through communication, collaboration, and cooperation with other individuals. The interaction from others may affect the power of an expert as well as his/her opinion. Furthermore, it is noted that a link path with the highest degree of trust is the most efficient information transmission channel. Inspired by these findings, an optimal trust-induced consensus process is designed with the usage of intuitionistic fuzzy preference relation. The comprehensive weight of each expert is decomposed into two portions, namely: 1) the individual weights and 2) interactive weights. Three optimization models are constructed to achieve weight parameters under different decision situations, where the weight parameters are represented through a 2-order additive fuzzy measure and the Shapley value. To reflect the interaction, the Choquet integral is employed for aggregating opinions, and a novel distance measure is adopted for accomplishing a consensus index. An illustrative example and comparison are put in practice to show the effectiveness and improvements of the proposed method.


Cancer incidence in a population living near a petrochemical facility and oil refinery.
There is growing concern that pollution from petrochemical and oil refinery installations in Pancevo (Serbia) has increased the incidence of various diseases including cancer. The aim of our study was to investigate cancer incidence in Pancevo and to compare it with the region of central Serbia. Cancer incidence data were obtained from the corresponding Serbian Cancer Registries. Systematic local monitoring of benzene, toluene and methyl mercaptane in the atmosphere within Pancevo's industrial area indicated that the average monthly and yearly concentrations often exceeded permitted levels proposed by EU standards (5 microgm(-3)). Cancer incidence was lower in Pancevo than in central Serbia (the standardised incidence for all types of cancers in Pancevo was 218.3 and in central Serbia it was 241.7 per 100,000 inhabitants). The available data do not allow us to correlate air pollution in Pancevo with increased cancer incidence.


Subjective and myographic responses in arm and leg cycle exercising.
A study was performed to explore possible psychological benefits of additional arm work during cycle exercising. For this, the subjective and physiological responses of 12 healthy young males were studied during arm and leg exercise on a cycle ergometer with movable arm levers (at 2 distances of the handgrips from the body) and during leg exercise with the grips fixed. After warming up, the subjects kept for 20 min. a constant work load leading to heart rates of about 150 to 160 beats.min.-1. Neither the EMG data nor the ratings of discomfort showed a substantial relief by arm work, but the subjects had different preferences for arm and leg exercise and just leg work, accompanied by differences in discomfort and physiological responses.