A Web-Based Toolkit to Provide Evidence-Based Resources About Crystal Methamphetamine for the Australian Community: Collaborative Development of Cracks in the Ice.
The use of crystal methamphetamine (ice) and the associated harms for individuals, families, and communities across Australia has been the subject of growing concern in recent years. The provision of easily accessible, evidence-based, and up-to-date information and resources about crystal methamphetamine for the community is a critical component of an effective public health response. This paper aims to describe the codevelopment process of the Web-based Cracks in the Ice Community Toolkit, which was developed to improve access to evidence-based information and resources about crystal methamphetamine for the Australian community. Development of the Cracks in the Ice Community Toolkit was conducted in collaboration with community members across Australia and with experts working in the addiction field. The iterative process involved the following: (1) consultation with end users, including community members, crystal methamphetamine users, families and friends of someone using crystal methamphetamine, health professionals, and teachers (n=451) via a cross-sectional Web-based survey to understand information needs; (2) content and Web development; and (3) user testing of a beta version of the Web-based toolkit among end users (n=41) and experts (n=10) to evaluate the toolkit's acceptability, relevance, and appeal. Initial end user consultation indicated that the most commonly endorsed reasons for visiting a website about crystal methamphetamine were "to get information for myself" (185/451, 41.0%) and "to find out how to help a friend or a family member" (136/451, 30.2%). Community consultation also revealed the need for simple information about crystal methamphetamine, including what it is, its effects, and when and where to seek help or support. Feedback on a beta version of the toolkit was positive in terms of content, readability, layout, look, and feel. Commonly identified areas for improvement related to increasing the level of engagement and personal connection, improving the ease of navigation, and balancing a "low prevalence of use, yet high impact" message. A total of 9138 users visited the website in the 3 months immediately post launch, and over 25,000 hard-copy Cracks in the Ice booklets and flyers were distributed across Australia. Of these resources, 60.93% (15,525/25,480) were distributed to relevant organizations and mailing list subscribers, and 39.07% (9955/25,480) were ordered directly by individuals, services, and community groups via the Cracks in the Ice website. The codevelopment process resulted in an engaging Web-based resource for the Australian community to access up-to-date and evidence-based resources about crystal methamphetamine. The Cracks in the Ice Community Toolkit provides much-needed information and support for individuals, families, and communities.


Ibudilast reduces oxaliplatin-induced tactile allodynia and cognitive impairments in rats.
Chemotherapy can cause serious neurotoxic side effects, such as painful peripheral neuropathies and disabling cognitive impairments. Four experiments examined whether Ibudilast, a clinically approved neuroimmune therapy, would reduce tactile allodynia and memory impairments caused by oxaliplatin in laboratory rats. Rats received an intraperitoneal injection of oxaliplatin (6mg/kg i.p.) or vehicle and were assessed for tactile allodynia 3 or 5days after injection, memory impairments in the novel object and novel location recognition tests 10-12days after injection, and fear conditioning 14days after injection. Ibudilast (7.5mg/kg) or vehicle was administered prior to oxaliplatin (Experiments 1 and 3) or prior to behavioural testing (Experiments 2 and 4). Ibudilast treatment prior to oxaliplatin prevented the development of tactile allodynia and memory impairments. Ibudilast treatment prior to behavioural testing reduced oxaliplatin-induced tactile allodynia, memory impairments, and impaired renewal of fear conditioning. These results suggest that Ibudilast could be an effective treatment against oxaliplatin-induced neuropathies and cognitive impairments.


Cytosolic calcium, hydrogen peroxide and related gene expression and protein modulation in Arabidopsis thaliana cell cultures respond immediately to altered gravitation: parabolic flight data.
Callus cell cultures of Arabidopsis thaliana (cv. Columbia) were exposed to parabolic flights in order to assess molecular, short-term responses to altered gravity fields. Using transgenic cell lines, hydrogen peroxide (H2 O2 ) and cytosolic Ca(2+) were continuously monitored. In parallel, the metabolism of samples was chemically quenched (RNAlater, Ambion for RNA; acid/base for NADPH, NADP) at typical stages of a parabola [1 g before pull up; end of pull up (1.8 g), end of microgravity (20 s) and end of pull out (1.8 g)]. Cells exhibited an increase in both Ca(2+) and H2 O2 with the onset of microgravity, and a decline thereafter. This behaviour was accompanied by a decrease of the NADPH/NADP redox ratio, indicating Ca(2+) -dependent activation of a NADPH oxidase. Microarray analyses revealed concomitant expression profiles. At the end of the microgravity phase, 396 transcripts were specifically up-, while 485 were down-regulated. Up-regulation was dominated by Ca(2+) - and ROS-related gene products. The same material was also used for analysis of phosphopeptides with 2-D SDS PAGE. Relevant spots were identified by liquid chromatography-MS. With the exception of a chaperone (HSP 70-3), hypergravity (1.8 g) and microgravity modified different sets of proteins. These are partly involved in primary metabolism (glycolysis, gluconeogenesis, citrate cycle) and detoxification of ROS. Taken together, these data show that both gene expression and protein modulation jointly respond within seconds to alterations in the gravity field, with a focus on metabolic adaptation, signalling and control of ROS.


Anesthetic Management of the Surgical Correction of Idiopathic Scoliosis in a Teenager With Ornithine Transcarbamalyse Deficiency.
Ornithine transcarbamylase (OTC) deficiency is the most common genetic disorder of the urea cycle. These disorders are characterized by an inability to metabolize ammonia into urea, leading to hyperammonemia with variable physiological consequences and presenting important anesthetic challenges, especially the perioperative prevention of hyperammonemia and management of its consequences, should it occur. Idiopathic scoliosis (IS) is the most common spinal deformity requiring surgical treatment. This paper presents the case of a 16-year-old female with OTC deficiency who underwent spinal fusion for IS. The chosen anesthetic strategy was combined anesthesia with total intravenous general anesthesia using target-controlled infusion pumps, an erector spinae plane block (ESPB), and a multi-pronged approach to ensure metabolic control while avoiding hyperammonemia. The existing literature regarding major surgery in patients with OTC deficiency is sparse, and this paper provides one of the first case reports of a scoliosis correction surgery, as well as one of the first descriptions of prolonged propofol infusion and locoregional anesthesia with an erector spinae plane block in this context.


Physiological stimulation enhances HRP marking of salivary neurons in rats.
Neurons of the superior salivary nucleus in rats have been labeled by retrograde transport of HRP injected into the lingual nerve. The nucleus is formed by a band of small, multipolar cells diagonally oriented in the lateral reticular formation of the caudal pons, just caudal to the root of the facial nerve. As time for transport of HRP was increased from 14 1/2 to 24 hr, the number of labeled cells increased exponentially along the curve, Y = 0.001 exp(0.51T), r = 0.995, to a maximum of 272 cells. Stimulating neuronal activity immediately after HRP injection, by swabbing the rat's mouth with 1% acetic acid, increased the number of labeled cells at 14 1/2 (p less than 0.05), 16, 18 and 20 (p less than 0.01) hr transport time. Counts of labeled cells in stimulated animals fell along a cumulative, normal distribution curve (ogive) with a mean at 18.2 hrs, S.D. 1.6 hr. Enhanced labeling of activated cells could be due to more rapid transport rates or to increased amounts of HRP transported.


Recent updates on the role of extracellular vesicles in the pathogenesis of allergic asthma.
Asthma is a chronic inflammatory disease of the airway diagnosed with different endotypes and phenotypes, characterized by airway obstruction in response to allergens, bacterial/viral infections, or pollutants. Several cell types such as the airway epithelial cells, mesenchymal stem cells and different immune cells including dendritic cells (DCs), T and B cells and mast cells play an essential role during the pathobiology of asthma. Extracellular vesicles (EVs) are membranous nanovesicles produced by every cell type that facilitates intercellular communications. EVs contain heterogeneous cargos that primarily depend on the composition or cell type of origin and they can alter the physiological state of the target cells. EVs encompass a wide variety of proteins including Tetraspanins, MHC classes I and II, co-stimulatory molecules, nucleic acids such as RNA, miRNA, piRNA, circRNA, and lipids like ceramides and sphingolipids. Recent literature indicates that EVs play a pivotal role in the pathophysiology of allergic asthma and may potentially be used as a novel biomarker to determine endotypes and phenotypes in severe asthmatics. Based on the prior reports, we speculate that regulation of EVs biogenesis and release might be under the control of circadian rhythms. Thus, circadian rhythms may influence the composition of the EVs, which alter the microenvironment that results in the induction of an immune-inflammatory response to various environmental insults or allergens such as air pollutants, ozone, diesel exhaust particles, pollens, outdoor molds, environmental tobacco smoke, etc. In this mini-review, we summarize the recent updates on the novel role of EVs in the pathogenesis of asthma, and highlight the link between circadian rhythms and EVs that may be important to identify molecular mechanisms to target during the pathogenesis of chronic inflammatory lung disease such as asthma.


Evaluation of endoscope sheaths as viral barriers.
Evaluate ENT endoscope sheaths as barriers to virus passage. "Defective" sheaths covering an endoscope were challenged with virus to determine how many virus particles could be recovered from the endoscope. Sheaths with small laser-drilled holes (2 to 30 microm) were challenged with high-titer virus suspensions (10(8) viruses/mL). The inside of the sheath and the endoscope were separately rinsed to recover any virus that penetrated through the hole in the sheath. In an attempt to assess the possible importance of holes in the sheaths, a sequential test was conducted with an initial virus challenge outside a defective sheath (30-micron hole in the sheath), after which the possibly contaminated endoscope was removed and inserted into a second defective sheath (with a 20-micron hole at the same location) to determine whether the contaminating virus would pass outward through the second sheath. Small volumes of virus-containing fluid penetrated through the hole, e.g., 500 virus particles passed through one of three 30-microm holes. A significant fraction of those virus particles was occasionally found on the endoscope after removal from the sheath. Similar results were obtained with sheaths that had small tears (34-84 microm in length, from punctures with fine wires). Although some virus penetration could occur during the initial challenge contaminating the endoscope, no virus was detected passing outward through the second sheath. Use of a sheath combined with intermediate level disinfection should provide a safe instrument for ENT endoscopy.


Spontaneous large-scale autolysis in Clostridium acetobutylicum contributes to generation of more spores.
Autolysis is a widespread phenomenon in bacteria. In batch fermentation of Clostridium acetobutylicum ATCC 824, there is a spontaneous large-scale autolysis phenomenon with significant decrease of cell density immediately after exponential phase. To unravel the role of autolysis, an autolysin-coding gene, CA_C0554, was disrupted by using ClosTron system to obtain the mutant C. acetobutylicum lyc::int(72). The lower final cell density and faster cell density decrease rate of C. acetobutylicum ATCC 824 than those of C. acetobutylicum lyc::int(72) indicates that CA_C0554 was an important but not the sole autolysin-coding gene responding for the large-scale autolysis. Similar glucose utilization and solvents production but obvious lower cell density of C. acetobutylicum ATCC 824 comparing to C. acetobutylicum lyc::int(72) suggests that lysed C. acetobutylicum ATCC 824 cells were metabolic inactive. On the contrary, the spore density of C. acetobutylicum ATCC 824 is 26.1% higher than that of C. acetobutylicum lyc::int(72) in the final culture broth of batch fermentation. We speculated that spontaneous autolysis of metabolic-inactive cells provided nutrients for the sporulating cells. The present study suggests that one important biological role of spontaneous large-scale autolysis in C. acetobutylicum ATCC 824 batch fermentation is contributing to generation of more spores during sporulation.


In vitro antiproliferative effects of nab-paclitaxel with liposomal cisplatin on MDA-MB-231 and MCF-7 breast cancer cell lines.
In this study, the in vitro cytotoxic effect of nanotechnological drugs nab-paclitaxel and liposomal cisplatin combination was evaluated on MDA-MB-231 and MCF-7 breast cancer cell lines. For this purpose cell viability, cell index values obtained from xCELLigence RTCA (Real-Time Cell Analysis) DP instrument, mitotic index (MI), apoptotic index (AI) and labelling index (LI) analysis among cell kinetic parameters were used. A1L25: 1 μg/ml nab-paclitaxel+25 μg/ml liposomal cisplatin, A1L5: 1 μg/ml nab-paclitaxel+5 μg/ml liposomal cisplatin and A10L5: 10 μg/ml nab-paclitaxel+5 μg/ml liposomal cisplatin for MDA-MB-231 cell line and A1L5: 1 μg/ml nab-paclitaxel+5 μg/ml liposomal cisplatin, A1L10: 1 μg/ml nab-paclitaxel+10 μg/ml liposomal cisplatin and A5L1: 5 μg/ml nab-paclitaxel+1 μg/ml liposomal cisplatin doses for MCF-7 were applied for 24-72 hrs. Significant decrease in cell viability and cell index values for both cell lines was observed, while the MI and LI values of both cell lines increased at 24 hrs, and decreased significantly at 72 hrs. Also there was a significant increase in the AI values. Nab-paclitaxel and liposomal cisplatin offer a promising treatment modality in different breast cancer subtypes.


Air-Stable, Lead-Free Zero-Dimensional Mixed Bismuth-Antimony Perovskite Single Crystals with Ultra-broadband Emission.
Lead-free zero-dimensional (0D) organic-inorganic metal halide perovskites have recently attracted increasing attention for their excellent photoluminescence properties and chemical stability. Here, we report the synthesis and characterization of an air-stable 0D mixed metal halide perovskite (C8 NH12 )4 Bi0.57 Sb0.43 Br7 ⋅H2 O, in which individual [BiBr6 ]3- and [SbBr6 ]3- octahedral units are completely isolated and surrounded by the large organic cation C8 H12 N+ . Upon photoexcitation, the bulk crystals exhibit ultra-broadband emission ranging from 400 to 850 nm, which originates from both free excitons and self-trapped excitons. This is the first example of 0D perovskites with broadband emission spanning the entire visible spectrum. In addition, (C8 NH12 )4 Bi0.57 Sb0.43 Br7 ⋅H2 O exhibits excellent humidity and light stability. These findings present a new direction towards the design of environmentally-friendly, high-performance 0D perovskite light emitters.


Predictors of Metastases in Rectal Neuroendocrine Tumors: Results of a National Cohort Study.
Rectal neuroendocrine tumors are often found incidentally. Local excision alone has been advocated for lesions ≤2 cm; however, the evidence base for this approach is limited. Associations among tumor size, degree of differentiation, and presence of distant metastatic disease were examined. This was a retrospective cohort study. This study was conducted using a nationwide cohort. A total of 4893 patients with rectal neuroendocrine tumors were identified in the National Cancer Database (2006-2015). Logistic regression analyses were used to evaluate associations among tumor size, degree of differentiation, and presence of regional and distant metastatic disease. Cut point analysis was performed to identify an optimal size threshold predictive of distant metastatic disease. Of patients included for analysis, 3880 (79.3%) had well-differentiated tumors, 540 (11.0%) had moderately differentiated tumors, and 473 (9.7%) had poorly differentiated tumors. On logistic regression, increasing size was associated with a higher likelihood of pathologically confirmed lymph node involvement (among patients undergoing proctectomy), and both size and degree of differentiation were independently associated with a higher likelihood of distant metastatic disease. The association between tumor size and distant metastatic disease was stronger for well-differentiated and moderately differentiated tumors (OR = 1.4; p < 0.001 for both) than for poorly differentiated tumors (OR = 1.1; p = 0.010). For well-differentiated tumors, the optimal cut point for the presence of distant metastatic disease was 1.15 cm (area under the curve = 0.88; 88% sensitive and 88% specific). Tumors ≥1.15 cm in diameter were associated with a substantially increased incidence of distant metastatic disease (72/449 (13.8%)). For moderately differentiated tumors, the optimal cut point was also 1.15 cm (area under the curve = 0.87, 100% sensitive and 75% specific). This study was limited by its retrospective design. Tumor size and degree of differentiation are predictive of regional and distant metastatic disease in rectal neuroendocrine tumors. Patients with tumors >1.15 cm are at substantial risk of distant metastasis and should be staged and managed accordingly. See Video Abstract at http://links.lww.com/DCR/A778.


Development of a population-specific regression equation to estimate total body water in hemodialysis patients.
We have previously shown that the impedance index (height corrected resistance) is a valid and reliable correlate of total body water (TBW) in hemodialysis patients. We estimated TBW by single frequency bioelectrical impedance analysis (BIA) in 3009 in-center hemodialysis patients, and developed an ESRD-specific TBW equation from routinely available demographic and anthropometric variables. The mean +/- SD age was 60.5 +/- 15.5 years; 47% were female, 47% African-American, and 36% diabetic. Dialysis duration was 3.8 +/- 3.7 years. Mean TBW was 40.8 +/- 9.3 kg, 56 +/- 9% of body weight. A stepwise linear regression equation was fit on a two-thirds random sample, deriving significant parameter estimates for the variables age, gender, height, weight, diabetic status, weight squared, and the cross-products of age and gender, age and weight, gender and weight, and height and weight. The equation was then validated in the remaining one-third sample, and compared with TBW estimates by the Watson and Hume-Weyer formulae. TBW estimated by our equation (40.6 +/- 8.6 kg) was not significantly different from the BIA TBW (40.5 +/- 9.3 kg). In contrast, TBW estimated by the Watson (37.0 +/- 7.6 kg) and Hume-Weyer (37.9 +/- 7.7 kg) formulae underestimated TBW by a mean of 3.5 and 2.6 kg, respectively. A population-specific equation provides superior prediction of TBW in hemodialysis patients. The use of formulae developed and validated in non-uremic populations may result in underestimates of TBW in patients with ESRD, and potentially, overestimates of dialysis dose approximated by the clearance-time to TBW ratio (Kt/V).


Cortactin knockdown results in disruption of basal TBCs and alters turnover of Sertoli cell ESs in Rattus norvegicus†.
Here we explore the prediction that long-term knockdown of cortactin (CTTN), a component of tubulobulbar complexes (TBCs), disrupts TBCs in Sertoli cells and alters the turnover of basal ectoplasmic specializations (ESs). In rats, intratesticular injections of siRNA targeting CTTN (siCTTN) in one testis and nontargeting siRNA (siControl) in the contralateral testis were done on days 0, 2, 4, 6, and 8. The experiment was terminated on day 9 and testes were analyzed by either western blotting, or by stimulated emission depletion (STED), electron and/or conventional fluorescence microscopy. Levels of CTTN were successfully knocked down in experimental testes compared to controls. When cryo-sections were labeled for actin filaments, or CTTN, and oxysterol binding protein-related protein 9 (ORP9) and analyzed by STED microscopy, TBCs were "less distinct" than in tubules of the same stages from control testes. When analyzed by electron microscopy, redundant clumps of basal actin filament containing ESs were observed in experimental sections. Using labeling of actin filaments in ESs, thresholding techniques were used to calculate the number of pixels above threshold per unit length of tubule wall in seminiferous tubules at Stage VII. Median values were higher in experimental testes relative to controls in the four animals analyzed. Although we detected subtle differences in ES turnover, we were unable to demonstrate changes in spermatocyte translocation or in the levels of junction proteins at the sites. Our results are the first to demonstrate that perturbation of basal TBCs alters the turnover of actin-related junctions (ESs).


[A study of synchronization of the sinus unit upon stimulation from auricles].
The excitation of the sinoatrial unit from heart auricles of the frog has been studied. Potentials were recorded by means of microelectrodes inserted to pacemaker of the sinoatrial unit. It has been established that auricles can impart the rhythm to the sinoatrial unit due to electric and electromechanical influence, and electromechanical influence is of greater significance. Specific transitions accompanying the establishment of the stationary rhythm have been studied. A mathematical model of transitions of the establishment of the rhythm of the sinoatrial unit, which is based on diophant methods is offered. The catculations performed by means of the mathematical model coincide well with results of experimental studies. The stabilizing role of auricles in the formation of the rhythm of the sinoatrial unit has been established.


Hydrogen-Bonding Motifs and Proton-Transfer Dynamics in Electronically Excited 6-Hydroxy-2-formylfulvene.
To elucidate low-barrier hydrogen-bonding (LBHBing) motifs and their ramifications for hydron-migration dynamics, the Ã1B2-X̃1A1 (π* ← π) absorption system of 6-hydroxy-2-formylfulvene (HFF) and its monodeuterated isotopolog (HFF-d) has been probed under free-jet expansion conditions through synergistic application of fluorescence-based laser spectroscopy and quantum-chemical calculations. Neither the donor-acceptor distance nor the proton-transfer barrier is predicted to change markedly between the X̃1A1 and Ã1B2 manifolds, yet a radical alteration in the nature of the reaction coordinate, whereby the planar (C2v) transition-state configuration of the former is supplanted by a notably aplanar (C2) form in the latter, is suggested to take place following π* ← π electron promotion (owing, in part, to attendant rearrangements of π-electron conjugation about the molecular framework). In contrast to the strongly perturbed vibrational landscape (commensurate with LBHBing) reported for the X̃1A1 potential surface, the present measurements have revealed surprisingly regular patterns of Ã1B2 vibronic structure which are devoid of obvious band shifts/splittings that would be indicative of efficient proton-transfer processes. Detailed analyses enabled a total of 41 (6) and 28 (5) excited-state vibrational levels (fundamentals) to be assigned for HFF and HFF-d, with extensive activity found for modes involving displacement of the seven-membered chelate ring that harbors the O-H···O reaction center. Quantitative simulations of partially resolved rotational contours for the HFF origin band showed the transition dipole moment to possess hybrid type-a/b character, thereby allowing the tunneling-induced bifurcation of the vibrationless Ã1B2 level to be extracted, Δ0Ã = 0.119(11) cm-1. This represents an enormous (>1000-fold) decrease over the analogous ground-state metric and implies a pronounced quenching of excited-state hydron migration, in keeping with the kinematic penalties that would be exacted by requisite heavy-atom motion along a putatively aplanar reaction coordinate.


Combined industrial wastewater treatment in anaerobic bioreactor posttreated in constructed wetland.
Constructed wetland (CW) with monoculture of Arundo donax L. was investigated for the posttreatment of anaerobic bioreactor (ABR) treating combined industrial wastewater. Different dilutions of combined industrial wastewater (20, 40, 60, and 80) and original wastewater were fed into the ABR and then posttreated by the laboratory scale CW. The respective removal efficiencies of COD, BOD, TSS, nitrates, and ammonia were 80%, 78-82%, 91.7%, 88-92%, and 100% for original industrial wastewater treated in ABR. ABR was efficient in the removal of Ni, Pb, and Cd with removal efficiencies in the order of Cd (2.7%) > Ni (79%) > Pb (85%). Posttreatment of the ABR treated effluent was carried out in lab scale CW containing A. donax L. CW was effective in the removal of COD and various heavy metals present in ABR effluents. The posttreatment in CW resulted in reducing the metal concentrations to 1.95 mg/L, 0 mg/L, and 0.004 mg/L for Ni, Pb, and Cd which were within the permissible water quality standards for industrial effluents. The treatment strategy was effective and sustainable for the treatment of combined industrial wastewater.


Surface Characterization of Mechanochemically Modified Exfoliated Halloysite Nanoscrolls.
Surface modifications fundamentally influence the morphology of kaolinite nanostructures as a function of crystallinity and the presence of contaminants. Besides morphology, the catalytic properties of 1:1-type exfoliated aluminosilicates are also influenced by the presence of defect sites that can be generated in a controlled manner by mechanochemical activation. In this work, we investigated exfoliated halloysite nanoparticles with a quasi-homogeneous, scroll-type secondary structure toward developing structural/functional relationships for composition, atomic structure, and morphology. The surface properties of thin-walled nanoscrolls were studied as a function of mechanochemical activation expressed by the duration of dry-grinding. The surface characterizations were carried out using N2, NH3, and CO2 adsorption measurements. The effects of grinding on the nanohalloysite structure were followed using thermoanalytical thermogravimetric/derivative thermogravimetric (TG/DTG) and infrared spectroscopic [Fourier transform infrared/attenuated total reflection (FTIR/ATR)] techniques. Grinding results in partial dehydroxylation with similar changes as those observed for heat treatment above 300 °C. Mechanochemical activation shows a decrease in the dehydroxylation mass loss and the DTG peak temperature, a decrease in the specific surface area and the number of mesopores, an increase in the surface acidity, blue shift of surface hydroxide bands, and a decrease in the intensity of FTIR/ATR bands as a function of the grinding time. The experimental observations were used to guide atomic-scale structural and energetic simulations using realistic molecular cluster models for a nanohalloysite particle. A full potential energy surface description was developed for the mechanochemical activation and/or heating toward nanometahalloysite formation that aids the interpretation of experimental results. The calculated differences upon dehydroxylation show a remarkable agreement with the mass loss values from DTG measurements.


Relationship between the serum uric acid level, visceral fat accumulation and serum adiponectin concentration in Japanese men.
Visceral fat accumulation is an underlying component of the metabolic syndrome (MetS). Hypoadiponectinemia is one of the key molecules of the MetS. In the present study, we investigated the relationship between the serum uric acid level, visceral fat accumulation and serum adiponectin concentration in Japanese men. The study group comprised 1,520 Japanese employed men (mean age: 45.6+/-10.4 years, +/- SD), who had undergone an annual health check-up both in 2004 and 2005. In addition to parameters measured in the annual health check-up, visceral fat area (VFA) and serum adiponectin concentration were measured by the bioelectrical impedance analysis method and a sandwich enzyme-linked immunosorbent assay (ELISA) system, respectively. Visceral fat accumulation was identified in 56.1% of the subjects with hyperuricemia. There was significant positive correlation between visceral fat area and serum uric acid levels (r=0.223, p<0.0001), and negative correlation between serum adiponectin concentration and serum uric acid levels (r=-0.198, p<0.0001). The one-year change in VFA was associated with the one-year change in serum uric acid levels. Stepwise multiple regression analysis showed that VFA and the serum adiponectin concentration were significant explanatory variables for serum uric acid levels. Hyperuricemia is significantly associated with visceral fat accumulation and hypoadiponectinemia in Japanese men.


Cervical necrotizing fasciitis in an uncontrolled type II diabetic patient.
We report a case of cervical necrotizing fasciitis (CNF) in a female having uncontrolled type II diabetes mellitus. The patient was presented to us after 20 days of preliminary symptoms. The aetiology of microbial inoculation in subdermal tissue was not known. The isolate was Staphylococcus aureus. In spite of the delay in presentation, the patient was successfully treated with combined antimicrobial and surgical intervention.


Granulocyte macrophage--colony-stimulating factor (GM-CSF) decreases CD1a expression by human Langerhans cells and increases proliferation in the mixed epidermal cell-lymphocyte reaction (MELR).
Langerhans cells (LC) undergo a variety of phenotypic and functional changes in vitro. To determine the effects of granulocyte macrophage--colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-alpha), and interleukin 1-alpha (IL-1) on LC phenotype in vitro, epidermal cell suspensions were enriched for LC by density-gradient centrifugation and cultured in the presence of 10 ng/ml of these cytokines. The percentage of cells expressing the surface protein CD1a was determined by flow cytometry. This percentage typically dropped after 48 h culture in both control and cytokine-treated medium to less than half that of the starting value. By the fifth day, the percentage of cells expressing CD1a in TNF-alpha and IL-1--treated cultures was still near half of the starting value, slightly above that of control cultures. Treatment with GM-CSF caused large and consistent decreases in the percentage of epidermal cells expressing CD1a. Cell viability in each of the three cytokine-treated cultures was identical to the control cultures, with essentially all cells having died by the sixth day after isolation. To determine the functional effects of these cytokines, the cytokine-containing medium was replaced after 72 h with medium containing purified allogeneic T cells and proliferation measured. Preliminary experiments showed no increased proliferation induced by IL-1 or TNF-alpha--treated epidermal cells. GM-CSF-treated epidermal cells induced 2-3 times more T-cell proliferation than epidermal cells cultured without additional cytokines. We conclude that GM-CSF, a cytokine known to be produced by keratinocytes in vitro, decreases CD1a expression by human LC and increases their ability to stimulate proliferation by allogeneic T cells.


Longer intestinal persistence of Enterococcus faecalis compared to Enterococcus faecium clones in intensive-care-unit patients.
The dynamics of intestinal colonization with enterococcal clones in intensive-care-unit (ICU) patients was evaluated. Eight patients admitted directly to the neurosurgical ICU at the Ramón y Cajal University Hospital (Madrid, Spain) from the community and with no overlapping stay during a 10-month period in 2006 were studied. Rectal swab specimens were collected on admission and daily until the patients were discharged. Clonality was determined by pulsed-field gel electrophoresis and multilocus sequence typing. Clonal colonization dynamics were estimated by using two new parameters: the clonal diversity per patient per day (CDPD) and the clonal persistence ratio (CPR). Enterococcus faecalis isolates (n = 123) and Enterococcus faecium isolates (n = 66) were resolved into 13 and 15 clones, respectively. The CDPD of E. faecalis steadily increased during admission, and E. faecalis showed a higher (P = 0.001) CPR value than E. faecium (0.86 and 0.42, respectively). E. faecium, with the exception of an ampicillin-resistant clone belonging to clonal complex 17, frequently appeared as a short-term colonizer, even though the E. faecalis clones had significantly (P = 0.03) more days under antibiotic exposure than E. faecium (77.5 and 65 days/100 colonization days, respectively). E. faecalis had a longer persistence than E. faecium, except for the CC17 ampicillin-resistant clone, and E. faecalis showed a cumulative increase in CDPD, whereas E. faecium did not. CDPD and CPR were useful for measuring the dynamics of intestinal colonization with enterococcal clones.


Analysis of large versus small pheochromocytomas: operative approaches and patient outcomes.
Laparoscopic adrenalectomy for small pheochromocytomas, although challenging, is widely accepted. However, its application to pheochromocytomas larger than 6 cm is questioned due to concerns of malignancy and case complexity. Our aim was to examine the impact of pheochromocytoma tumor size (>/=6 cm vs <6 cm) on operative approach and postoperative patient outcomes. A retrospective review of adrenalectomies performed at 3 university hospitals over 1 decade was analyzed. All pheochromocytomas were identified and then divided based on size into large (>/=6 cm) and small (<6 cm) groups. We examined patient and tumor demographics, pathologic diagnosis, operative approach (laparoscopic vs open), postoperative complications, and biochemical cure rates. Data were analyzed using the Student t test and Fisher exact test with a P value <.05 considered significant. From 1995 to 2005, 65 pheochromocytomas were resected. Of the total, 38% (n = 25) tumors were >/=6 cm and 62% (n = 40) were <6 cm. For the large tumors, 1 out of 25 (4%) was malignant, whereas no small tumors were malignant. There was no statistically significant increased risk of malignancy in tumors >/=6 cm in size (P = .31). Initial operative approach was based on surgeon preference. Of the adrenalectomies performed, 88% were laparoscopic, with 3 of 25 (12%) large tumors requiring conversion from laparoscopic to open for intraoperative bleeding. None of the small tumors required conversion. No major postoperative complications (eg, stroke or myocardial infarction) occurred in either group. Minor complications (eg, wound infections and hematomas) were noted in 16% of large tumors and 12.5% of small tumors (P = .45). A total of 96% (24 of 25) patients with large tumors and 100% with small tumors showed postoperative biochemical cure. Tumor recurrence was noted in 1 patient with a tumor <6 cm. Pheochromocytomas >/=6 cm pose a challenge for laparoscopic resection, and concerns have been raised about the validity of this operative approach. This study demonstrates that there is no significant difference in the rate of malignancy for pheochromocytomas >/=6 cm versus <6 cm. There also were no significant differences identified in complication rates, postoperative biochemical cures, or tumor recurrence rates between these groups. Laparoscopic resection of pheochromocytomas can be safely accomplished regardless of size in centers with surgeons experienced in these procedures.


Advances in anatomical visualization on the head and neck through robotic surgery: A Brazilian perspective.
Trans Oral Robotic Surgery (TORS) is an emerging technique that provides several benefits over existing treatment regimens for head and neck cancer, including smaller incisions, less bleeding, shorter term inpatient hospitalization, and reduced intensive care unit (ICU) length of stay. TORS allows a high resolution, magnified, three-dimensional wide view of the surgical field through an endoscope, avoiding large external cervical incisions and split-lip mandibulotomy, usually required in cancer surgeries of the oropharynx. The anatomy of the Oropharynx viewed from the perspective of the robotic surgeon is different from the anatomy taught in medical schools and residence/fellowship programs, which is more directly related to emergency procedures, open field surgery, and imaging exams. Developing an understanding of the anatomic relationships and landmarks from the "inside out" perspective is critical for any surgeon willing to perform surgical procedures through a transoral robotic approach. Here we address the major anatomic landmarks and structures in head and neck robotic surgeries and advantages and disadvantages of this approach. We emphasize the importance of imaging for successful outcomes, pointing out important anatomic landmarks considered as blind spots for surgeons in clinical and endoscopic evaluations. We also describe the Brazilian current scenario and future perspectives of Robotic Surgery in terms of training and access to this technique, including institutions that currently offer this service in the different regions of Brazil.


The Gaze-Cueing Effect in the United States and Japan: Influence of Cultural Differences in Cognitive Strategies on Control of Attention.
The direction of gaze automatically and exogenously guides visual spatial attention, a phenomenon termed as the gaze-cueing effect. Although this effect arises when the duration of stimulus onset asynchrony (SOA) between a non-predictive gaze cue and the target is relatively long, no empirical research has examined the factors underlying this extended cueing effect. Two experiments compared the gaze-cueing effect at longer SOAs (700 ms) in Japanese and American participants. Cross-cultural studies on cognition suggest that Westerners tend to use a context-independent analytical strategy to process visual environments, whereas Asians use a context-dependent holistic approach. We hypothesized that Japanese participants would not demonstrate the gaze-cueing effect at longer SOAs because they are more sensitive to contextual information, such as the knowledge that the direction of a gaze is not predictive. Furthermore, we hypothesized that American participants would demonstrate the gaze-cueing effect at the long SOAs because they tend to follow gaze direction whether it is predictive or not. In Experiment 1, American participants demonstrated the gaze-cueing effect at the long SOA, indicating that their attention was driven by the central non-predictive gaze direction regardless of the SOAs. In Experiment 2, Japanese participants demonstrated no gaze-cueing effect at the long SOA, suggesting that the Japanese participants exercised voluntary control of their attention, which inhibited the gaze-cueing effect with the long SOA. Our findings suggest that the control of visual spatial attention elicited by social stimuli systematically differs between American and Japanese individuals.


QSAR Modeling is not "Push a Button and Find a Correlation": A Case Study of Toxicity of (Benzo-)triazoles on Algae.
A case study of toxicity of (benzo)triazoles ((B)TAZs) to the algae Pseudokirchneriella subcapitata is used to discuss some problems and solutions in QSAR modeling, particularly in the environmental context. The relevance of data curation (not only of experimental data, but also of chemical structures and input formats for the calculation of molecular descriptors), the crucial points of QSAR model validation and the potential application for new chemicals (internal robustness, exclusion of chance correlation, external predictivity, applicability domain) are described, while developing MLR-OLS models based on molecular descriptors, calculated by various QSAR software tools (commercial DRAGON, free PaDEL-Descriptor and QSPR-THESAURUS). Additionally, the utility of consensus models is highlighted. This work summarizes a methodology for a rigorous statistical approach to obtain reliable QSAR predictions, also for a large number of (B)TAZs in the ECHA preregistration list of REACH (even if starting from limited experimental data availability), and has evidenced some ambiguities and discrepancies related to SMILES notations from different databases; furthermore it highlighted some general problems related to QSAR model generation and was useful in the implementation of the PaDEL-Descriptor software.


Presynaptic effects of melatonin on norepinephrine release and uptake in rat pineal gland.
The effect of melatonin injection on norepinephrine (NE) turnover rate in rat pineal gland was estimated from the decline of tissue NE levels after the injection of the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine. The administration of a single injection of 300 micrograms/Kg of melatonin at the beginning of the scotophase induced, 3 hr later, a significant decrease of pineal NE turnover. The possible direct effect of melatonin on pineal NE release was examined in vitro. Exposure of rat pineal explants previously loaded with 3H-NE to 10(-8)-10(-6) M melatonin decreased significantly 3H-NE release triggered by 60 mM K+. This activity of melatonin was revealed only in pineals excised at night (0000 and 0400, i.e., at the fourth or eighth hours of darkness) and not in those excised in the middle (1400) or late light phase of the daily photoperiod (2000). Melatonin did not modify the spontaneous pineal 3H-NE efflux. Melatonin decreased 3H-NE uptake at a low NE concentration (0.5 microM) in a dose-dependent manner (IC50 identical to 10(-10) M). A kinetic analysis of the pineal NE uptake process indicated that melatonin augmented both Vmax and Km of transmitter uptake. These results suggest that endogenously released melatonin may be a regulatory signal for rat pineal sympathetic synapses.


Re-docking scheme for generating near-native protein complexes by assembling residue interaction fingerprints.
Interaction profile method is a useful method for processing rigid-body docking. After the docking process, the resulting set of docking poses could be classified by calculating similarities among them using these interaction profiles to search for near-native poses. However, there are some cases where the near-native poses are not included in this set of docking poses even when the bound-state structures are used. Therefore, we have developed a method for generating near-native docking poses by introducing a re-docking process. We devised a method for calculating the profile of interaction fingerprints by assembling protein complexes after determining certain core-protein complexes. For our analysis, we used 44 bound-state protein complexes selected from the ZDOCK benchmark dataset ver. 2.0, including some protein pairs none of which generated near-native poses in the docking process. Consequently, after the re-docking process we obtained profiles of interaction fingerprints, some of which yielded near-native poses. The re-docking process involved searching for possible docking poses in a restricted area using the profile of interaction fingerprints. If the profile includes interactions identical to those in the native complex, we obtained near-native docking poses. Accordingly, near-native poses were obtained for all bound-state protein complexes examined here. Application of interaction fingerprints to the re-docking process yielded structures with more native interactions, even when a docking pose, obtained following the initial docking process, contained only a small number of native amino acid interactions. Thus, utilization of the profile of interaction fingerprints in the re-docking process yielded more near-native poses.


Cardiorespiratory function.
ACCURATE EVALUATION OF THE DEGREE OF IMPAIRMENT OF PULMONARY FUNCTION IN PERSONS WITH FIBROSIS AND EMPHYSEMA REQUIRES: (1) ventilatory measurements from rapid spirogram tracings (vital capacity, maximal breathing capacity and the time required to blow the air from the lungs); (2) determination of the degree of bronchospasm present; (3) determination of the degree of pulmonary emphysema (residual air expressed quantitatively as percent of total lung volume); (4) determination of the arterial blood oxygen saturation at rest and immediately after step-up exercise; (5) measurement of the oxygen extraction from inspired air (per cent of oxygen removed) during rest and exercise; (6) determination of the oxygen up-take during exercise; and (7) observation of the duration of dyspnea after step-up exercise. No single physiologic test is adequate in evaluating impairment of pulmonary function, and roentgenograms of the chest are unreliable as a sole basis for appraisal of disability. In industrial medicine, pulmonary function studies make possible (a) more accurate diagnosis and evaluation of pulmonary disability; and (b) earlier detection and thus prevention of prolonged exposure by susceptible individuals to environmental hazards.


[Distinctive features of the anxiety state development in experimental model of posttraumatic stress disorder in the prenatally stressed male rats].
Anxious-depressive state was studied in experimental "stress-restress" model of posttraumatic stress disorder (PTSD) using adult rat males. Rat males were born by control females and whose mothers were under 60-minute immobilization stress since 15 until 19 days of pregnancy. Then rats were exposed to a single session of prolonged stress (restraint followed by a forced swim and exposure to ether vapors) and restressed 7 days later. 10 and 20 days after restress animals were tested in elevated plus-maze to measure anxiety and forced swim test to research depression-like behavior. In both groups there were control animal that stay intact. In addition to behavior, we studied activity of hypothalamo-pituitary-adrenal axis (basal activity and fast feedback inhibition) by analysis of plasma corticosterone concentration. We found that in control and prenatally stressed (PS) rat males in 10 days after stress have pathological state such as elevated anxiety and depressive-like behavior and inhibition of stress activity of H PA axis due to activation of fast feedback. However, in PS rats signs of disorder were deeper and longer--decreased basal plasma corticosterone and increased anxiety those saved in 20 days after restress. In conclusion, we can say that prenatal stress promotes developing of stronger behavioral and hormonal pathology in "stress-restress" paradigm.


The association between RhoB and caspase-2: changes with lovastatin-induced apoptosis.
Because cytoskeletal actin is regulated, in part, by Rho, and because Rho and caspases are involved in apoptosis, we sought to determine whether there was an association between RhoB and caspase-2. A RhoB-caspase-2 association was consistently demonstrated in neonatal mouse cardiomyocytes with Western Blotting, either after immunoprecipitation with RhoB followed by immunoblotting with caspase-2, or in reciprocal experiments after immuno precipitation with caspase-2 and immunoblotting with RhoB (n = 14). Although the RhoB-caspase-2 complex was constitutively present, the link between RhoB and caspase-2 may be operative in apoptosis because the HMG-CoA reductase inhibitor lovastatin increased the RhoB-caspase complex, especially in the nuclear fraction of the cell, with a peak occurrence 2 h after treatment. This association was unaffected by the caspase-2 inhibitor zVDVAD. Lovastatin produced apoptosis that was accompanied by an activation of caspase-2, as demonstrated by its immunohistochemistry and by the fact that the caspase-2 inhibitor zVDVAD reduced lovastatin-induced apoptosis. Lovastatin induced dramatic changes in cell morphology and a reduction in F-actin. Immunoblotting for actin suggests that lovastatin does not induce a degradation of the actin molecule, but rather affects filamentous F-actin. Caspase-2 inhibition with zVDVAD reduced lovastatin-induced alteration in cytoskeletal F-actin. The Rho inhibitor, Clostridium difficile toxin B, blunted the ability of lovastatin to induce apoptosis. In summary, these data show a previously unrecognized association between RhoB and caspase-2 in the cytosolic and nuclear fractions, which has ramifications for processes regulated by RhoB and caspase-2, including apoptosis.


The impact of the Baltic Germans' emigration on the pharmaceutical sector in Latvia (1939-1940).
For several hundred years, the Baltic German families of pharmacists have been the decisive creator of traditions in Latvian pharmacy. A large amount of the oldest pharmacies in Latvia, especially in Riga, were owned by pharmacists of Baltic German origin. Many of these ancient pharmacies ceased to exist in 1939, as a result of the emigration of the Baltic Germans. The agreement on the outward migration of German nationality citizens between Latvia and Germany was signed October 30, 1939. According to the information of the Pharmacy Board of Latvia, the number of employees in the pharmaceutical sector, registered in 1939, was 2068 persons. During the first wave of emigration, at the end of the year 1939, 306 persons, related to pharmacy, renounced the Latvian citizenship and emigrated. During the second wave of emigration, in spring of 1941, when Latvia had already lost its political independence, another 49 pharmaceutic employees left Latvia. In total 355 employees emigrated to Germany. As a result of the Baltic German emigration there was a decreased number of pharmacies in Latvia and the lack of pharmacists became a local issue. In rural areas quite often the only one pharmacy, which had been owned by a German origin pharmacist was liquidated or stayed closed for several months.


Antimicrobial Effects of Silver Nanoparticles Synthesized by Fatsia japonica Leaf Extracts for Preservation of Citrus Fruits.
Due to their potent antimicrobial activity, silver nanoparticles (AgNPs) synthesized by biomass might be promising in food preservation, whereas effects of AgNPs on Penicillium italicum-induced rot of Citrus fruits have not been investigated. In this study, a novel AgNPs biosynthesis method was developed based on Fatsia japonica leaf extracts. It was revealed that concentrations of leaf extracts, AgNO3 and NaCl affected AgNPs yields and particle sizes obviously. Under the optimized conditions (8 mg/mL extracts, 2 mM AgNO3 and 1 mM NaCl), AgNPs, synthesized within 80 min, showed potent preservative effect against P. italicum-induced rot of Citrus fruits. Furthermore, inhibition test and TEM analysis indicated that as-synthesized AgNPs caused cell deformation, cytoplasmic leakage, and thereupon cell death of P. italicum. Moreover, AgNPs had significant antibacterial activities against Escherichia coli and Staphylococcus aureus, which might be beneficial for Citrus fruits preservation. Altogether this study develops an efficient AgNPs synthesis method and a novel preservation method for Citrus fruits.


[Pleiotropic effects of statins].
The advent of statin therapy has revolutionized the ability of the clinician to manage patients at risk for the development of an ischemic event due to dyslipidemia. Large-scale clinical trials involving thousands of patients in both primary and secondary prevention have clearly demonstrated that statin therapy will reduce cardiovascular mortality across a broad spectrum of patient subgroups. However, the precise mechanism underlying the benefit of statin therapy has been controversial due to the multiplicity of potential benefits that statins have demonstrated in addition to pure lipid lowering. Recent experimental evidence supports the premise that clinical benefits are related primarily to pleiotropic effects of statins (endothelial function, inflammation, coagulation and plaque vulnerability).


Description of a novel HLA-DRB1 allele, DRB1*1207.
A new DRB1 allele has been identified during routine HLA-DRB1 generic typing with sequence specific oligonucleotides. The new allele was confirmed by PCR-restriction fragment length polymorphism analysis and subsequently sequenced. This showed the novel allele, named HLA-DRB1*1207, was similar in sequence to DRB1*12011, except for codon 69 of exon 2.


The trends of composite environmental indices in Korea.
In this paper we construct for the first time an annual Composite Environmental Index from 1986 to 1995 in Korea, which is useful for evaluating the efficiency of environmental policies. Nine types of environmental problems are examined. On average, the composite index has increased annually by 5.3% over the 1986-1995 period, which implies that overall environmental quality has deteriorated gradually during this period. Problems such as the greenhouse effect, loss of biodiversity, natural resource depletion, and ecotoxication led to deterioration of environmental quality in the 1990s.


FLUCTUATING ASYMMETRY IN CENTRAL AND MARGINAL POPULATIONS OF LYCHNIS VISCARIA IN RELATION TO GENETIC AND ENVIRONMENTAL FACTORS.
Developmental instability in the form of increased fluctuating asymmetry can be caused by either genetic or environmental stress. Because extinctions can be attributed broadly to these factors, fluctuating asymmetry may provide a sensitive tool for detecting such stresses. We studied the level of fluctuating asymmetry of flowers of a perennial outcrossing plant species, Lychnis viscaria, both in natural and common-garden populations. The degree of flower asymmetry was higher in small, isolated, and marginal populations of the species range. These marginal populations also were the most homozygous. In the core area of the species' range, flowers were more symmetrical The level of asymmetry was correlated with both population size and heterozygosity. However, a partial correlation analysis revealed that when the impact of population size was controlled for, there was a negative relationship between fluctuating asymmetry and heterozygosity, whereas when controlling for heterozygosity, no relationship between population size and fluctuating asymmetry was found. This indicates that genetic consequences of small population size probably underlie the relationship between the level of asymmetry and population size. Results from a transplantation experiment showed that individuals subjected to a higher environmental stress had an increased level of asymmetry compared to control plants. In the common-garden conditions the level of fluctuating asymmetry did not differ between the central and marginal populations. This suggests that presumably both genetic and environmental factors affected to the higher level of asymmetry among marginal populations compared to central ones. In all we conclude that even though fluctuating asymmetry seems to be a sensitive tool for detecting stresses, results from studies focusing on only one factor should be interpreted with caution.


Microsolvation of the Redox-Active Tyrosine-D in Photosystem II: Correlation of Energetics with EPR Spectroscopy and Oxidation-Induced Proton Transfer.
Photosystem II (PSII) of oxygenic photosynthesis captures sunlight to drive the catalytic oxidation of water and the reduction of plastoquinone. Among the several redox-active cofactors that participate in intricate electron transfer pathways there are two tyrosine residues, YZ and YD. They are situated in symmetry-related electron transfer branches but have different environments and play distinct roles. YZ is the immediate oxidant of the oxygen-evolving Mn4CaO5 cluster, whereas YD serves regulatory and protective functions. The protonation states and hydrogen-bond network in the environment of YD remain debated, while the role of microsolvation in stabilizing different redox states of YD and facilitating oxidation or mediating deprotonation, as well the fate of the phenolic proton, is unclear. Here we present detailed structural models of YD and its environment using large-scale quantum mechanical models and all-atom molecular dynamics of a complete PSII monomer. The energetics of water distribution within a hydrophobic cavity adjacent to YD are shown to correlate directly with electron paramagnetic resonance (EPR) parameters such as the tyrosyl g-tensor, allowing us to map the correspondence between specific structural models and available experimental observations. EPR spectra obtained under different conditions are explained with respect to the mode of interaction of the proximal water with the tyrosyl radical and the position of the phenolic proton within the cavity. Our results revise previous models of the energetics and build a detailed view of the role of confined water in the oxidation and deprotonation of YD. Finally, the model of microsolvation developed in the present work rationalizes in a straightforward way the biphasic oxidation kinetics of YD, offering new structural insights regarding the function of the radical in biological photosynthesis.


Assessing the Validity and Reproducibility of an Iron Dietary Intake Questionnaire Conducted in a Group of Young Polish Women.
The aim of the study was to analyse a designed brief iron dietary intake questionnaire based on a food frequency assessment (IRONIC-FFQ-IRON Intake Calculation-Food Frequency Questionnaire), including the assessment of validity and reproducibility in a group of 75 Polish women aged 20-30 years. Participants conducted 3-day dietary records and filled in the IRONIC-FFQ twice (FFQ1-directly after the dietary record and FFQ2-6 weeks later). The analysis included an assessment of validity (comparison with the results of the 3-day dietary record) and of reproducibility (comparison of the results obtained twice-FFQ1 and FFQ2). In the analysis of validity, the share of individuals correctly classified into tertiles was over 50% (weighted κ of 0.36), while analysis of correlation revealed correlation coefficients of almost 0.5. In the assessment of reproducibility, almost 80% of individuals were correctly classified and less than 3% were misclassified (weighted κ of 0.73), while a correlation coefficient higher than 0.85 was obtained. Both in the assessment of validity and of reproducibility, a Bland-Altman index of 6.7% was recorded (93.3% of compared pairs of results were in the acceptable range, attributed to differences within ± 2SD limit). Validation of the IRONIC-FFQ revealed a satisfactory level of validity and positively validated reproducibility.


Malignant paraganglioma of the posterior mediastinum: A case report with genetic analysis.
Paraganglioma and pheochromocytoma are rare neuroendocrine neoplasms that originate from chromaffin cells. In many of these tumors, several mutations are reported to occur in the genes of germline and/or somatic cells. A case of paraganglioma in the posterior mediastinum with highly malignant potential is reported. The patient had a rapid clinical course, and it was difficult to reach the final diagnosis. The initial diagnosis on fine-needle aspiration biopsy was a gastrointestinal stromal tumor (GIST) arising from the esophagus. Although radiation therapy was effective for the main tumor, the lung metastases did not respond sufficiently to several tyrosine kinase inhibitors. Autopsy and immunohistochemical examination using a battery of different markers resulted in a final diagnosis of malignant paraganglioma. Next-generation sequencing revealed several gene mutations and copy number variations, including of fumarate hydratase (FH), neurofibromatosis type-1 (NF1) and RET. Those gene alterations may contribute to the pathogenesis of this malignant phenotype to a certain extent. To confirm this, further cases and studies are required. In addition, it should be noted that histological examination of a small piece of tumor might have sampling bias and could cause misdiagnosis.


Sodium butyrate regulates Th17/Treg cell balance to ameliorate uveitis via the Nrf2/HO-1 pathway.
Autoimmune uveitis, a group of potentially blinding intraocular inflammatory diseases, remains a therapeutic challenge for ophthalmologists. Butyrates, which belong to the short-chain fatty acid family, possess immunomodulatory properties and therapeutic potential in several inflammatory disorders. However, the roles of butyrates in uveitis and their underlying immunomodulatory mechanisms remain elusive. Here, we report that treatment with sodium butyrate (NaB) significantly attenuated the ocular inflammatory response in mice with experimental autoimmune uveitis (EAU) at 14days after immunization, with significant decreases in inflammatory cell infiltration and inflammatory cytokine production in the retinas. Furthermore, NaB treatment decreased the frequency and number of Th17 cells and increased the frequency and number of T regulatory (Treg) cells in both draining lymph nodes and spleens of EAU mice. In vitro, NaB treatment directly converted the differentiation of naive T cells from Th17 cells toward Treg cells. Mechanistically, the NaB-mediated inhibition of Th17 cell differentiation may occur via inhibition of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1)/interleukin-6 receptor pathway. Moreover, the NaB-mediated inhibition on Th17 cell differentiation and uveitis were abrogated when an HO-1 inhibitor, SnPP, was used. These findings suggest that NaB inverts the differentiation of Th17 cells toward Treg cells and attenuates experimental autoimmune uveitis by modulating the Nrf2/HO-1 pathway.


High Resolution Quantitative Trait Locus Mapping and Whole Genome Sequencing Enable the Design of an Anthocyanidin Reductase-Specific Homoeo-Allelic Marker for Fruit Colour Improvement in Octoploid Strawberry (Fragaria × ananassa).
Fruit colour is central to the sensorial and nutritional quality of strawberry fruit and is therefore a major target in breeding programmes of the octoploid cultivated strawberry (Fragaria × ananassa). The red colour of the fruit is caused by the accumulation of anthocyanins, which are water-soluble flavonoids. To facilitate molecular breeding, here we have mapped with high resolution fruit colour quantitative trait loci (QTLs) (COLOUR, scored visually as in selection programmes) and associated flavonoid metabolic QTLs (5 anthocyanins compounds together with 8 flavonols and flavan-3-ols) to specific subgenomes of cultivated strawberry. Two main colour-related QTLs were located on the LG3A linkage group (Fragaria vesca subgenome). Genetic mapping, transcriptome analysis and whole genome sequencing enabled the detection of a homoeo-allelic variant of ANTHOCYANIDIN REDUCTASE (ANR) underlying the major male M3A COLOUR and pelargonidin-3-glucoside (PgGs) QTLs (up to ∼20% of explained variance). Consistent with previously published functional studies, ANR transcript abundance was inversely related with PgGs content in contrasted progeny individuals. Genetic segregation analyses further indicated that a molecular marker designed using an 18 bp deletion found in the 5'UTR of the candidate ANR homoeo-allelic variant is effective in identifying genotypes with intense red fruit colour. Our study provides insights into the genetic and molecular control of colour-related traits in strawberry and further defines a genetic marker for marker-assisted selection of new strawberry varieties with improved colour. The QTLs detected and the underlying candidate genes are different from those described to date, emphasising the importance of screening a wide diversity of genetic resources in strawberry.


Gastric ectopic pancreas combined with synchronous multiple early gastric cancer: A rare case report.
A large percentage of patients with ectopic pancreas are asymptomatic. When present, the symptoms are typically non-specific. These lesions are predominantly located in the stomach and benign in nature. Synchronous multiple early gastric cancer (SMEGC) (two or more simultaneous malignant lesions with early gastric cancer) is relatively rare and particularly easy to overlook during endoscopic examination. The prognosis of SMEGC is generally poor. We report a rare case of ectopic pancreas with concomitant SMEGC. A 74-year-old woman presented with paroxysmal upper abdominal pain. On initial investigations, she tested positive for Helicobacter pylori (H. pylori). She underwent esophagogastroduodenoscopy which revealed a 1.5 cm × 2 cm major lesion at the greater curvature and a 1 cm minor lesion at the lesser curvature of the stomach. On endoscopic ultrasound, the major lesion showed hypoechoic changes, uneven internal echoes and unclear boundaries between some areas and the muscularis propria. Endoscopic submucosal dissection was performed to excise the minor lesion. A laparoscopic resection was chosen for the major lesion. On histopathological examination, the major lesion contained high grade intraepithelial neoplasia with a small focus of cancer. A separate underlying ectopic pancreas was found under this lesion. The minor lesion contained high grade intraepithelial neoplasia. In this case, the patient was diagnosed with SMEGC with concomitant ectopic pancreas in the stomach. Patients with atrophy, H. pylori, and other risk factors should be carefully investigated to avoid missing other lesions including SMEGC and ectopic pancreas.


Implementing Behavioral Activation and Life-Steps for Depression and HIV Medication Adherence in a Community Health Center.
Antiretroviral therapy to treat HIV/AIDS has substantially improved clinical outcomes among patients living with HIV/AIDS, but only in the presence of very consistent adherence. One of the most prevalent and impactful individual-level predictors of poor adherence is depressive symptoms, even at subthreshold levels. Evidence-based cognitive behavioral interventions exist to address improvements in depressive symptoms and adherence in this population, yet these techniques have largely been designed and tested as individual treatments for delivery in mental health settings. This presents a significant challenge when transporting these techniques to medical settings where other formats for delivery may be more appropriate (i.e., groups, less frequent visits) and few hands-on resources exist to guide this process. As such, primary aims of this study were to adapt and implement evidence-based cognitive behavioral techniques for depression (behavioral activation; BA) and HIV medication adherence (Life-Steps) that have potential for dissemination in an outpatient community health center. The intervention incorporated feedback from health center staff and utilized a modular, group format that did not rely on sequential session attendance. Feasibility was examined over 8 weeks (n = 13). Preliminary effects on depression, health-related quality of life, and medication adherence were examined and exit interviews were conducted with a subset of participants (n = 4) to inform future modifications. Treatment descriptions and recommendations for effective clinical implementation based on patient and clinician feedback are provided along with case material of two individual patients and an example group session. Current efforts are an important next step for disseminating evidence-based techniques for depression and HIV medication adherence to community health center or AIDS service organization settings.


Pharmacokinetic approach to the clinical use of lidocaine intravenously.
The time course of lidocaine plasma concentrations following various modes of administration were predicted by computer. Initiating therapy with a single intravenous bolus dose was unsatisfactory; plasma levels during the first hour were potentially toxic after a 200-mg bolus and subtherapeutic after a 50- to 100-mg bolus. After two bolus doses of 100 mg, separated by 20 to 30 minutes, or a rapid loading infusion over 15 to 60 minutes, therapeutic concentrations were achieved and maintained. Pharmacokinetic principles can be of value in devising rational approaches to lidocaine dosage.


Isotyping and quantitation of the humoral immune response to SARS-CoV-2.
Understanding the immune response to SARS-CoV-2 is important for development of effective diagnostics and vaccines. We report here a broad antibody response to SARS-CoV-2 spike protein receptor binding domain (RBD) in 100 convalescent patient plasma samples. Antibody isotypes IgA, IgM, and IgG exhibited significantly higher anti-RBD titers when compared to SARS-CoV-2 negative controls. IgG subtyping indicated IgG1 and IgG3 to be most abundant. Greater than 90 % of SARS-CoV-2 positive plasma samples tested exhibited significant neutralization capacity using a surrogate virus neutralization assay. Of the IgG subclasses, IgG1 and IgG3 exhibited the highest viral neutralization capacity; whereas, IgG2 and IgG4 viral neutralization was not observed. Comparison of SARS-CoV-2 elicited total IgG binding to emerging variant (alpha, beta, and delta) RBDs indicated decreased binding. Furthermore, neutralization by SARS-CoV-2 convalescent plasma of delta and omicron variant RBDs was significantly decreased suggesting that neutralizing antibodies in convalescent plasma are less effective in inhibiting variants currently in circulation.


Limb ischemic postconditioning protects myocardium from ischemia-reperfusion injury.
To test the hypothesis that limb ischemic postconditioning protects the myocardium from reperfusion injury, and examine the mechanism involved. Forty rabbits were randomly divided into four groups: Control, Ischemic Preconditioning, Ischemic Postconditioning and Remote Postconditioning. Myocardial infarct size and tissue myeloperoxidase activity were determined at the end of the experiment. Plasma creatine kinase and malondialdehyde activity were measured at baseline, the end of ischemia, and after 3 h of reperfusion respectively. Myocardial infarct size was significantly reduced in Ischemic Preconditioning, Ischemic Postconditioning and Remote Postconditioning as compared to Control (p < 0.01). Results were confirmed by plasma creatine kinase activity. Plasma malondialdehyde was significantly less at 3 h of reperfusion in Ischemic Preconditioning, Ischemic Postconditioning and Remote Postconditioning than that in Control (p < 0.01). Neutrophil accumulation (myeloperoxidase activity) in the area at risk was less in Ischemic Preconditioning, Ischemic Postconditioning and Remote Postconditioning than that in Control (p < 0.01). Remote postconditioning reduces myocardial infarction in rabbits. The mechanism involved might be reduced oxygen radical-induced injury and improved antioxidant action.


Retained Skeletal Effects of Zoledronic Acid Following Discontinuation of Treatment: A Review of the Literature.
To evaluate the effects on bone mineral density (BMD), bone turnover markers (BTMs), and fracture incidence following zoledronic acid (ZOL) discontinuation. A search of PubMed (1966-May 2016) and International Pharmaceutical Abstracts (1970-May 2016) was conducted using the MeSH terms zoledronic acid, osteoporosis, and withholding treatment. Free text searches included drug holiday and drug discontinuation. An initial review yielded 87 articles. Six articles, which addressed the skeletal effects of ZOL after discontinuation of treatment, were included in the final review. ZOL is a widely prescribed bisphosphonate agent. Studies have shown that discontinuation of ZOL may have lasting skeletal benefits. However, there is inconsistent evidence regarding the duration of the residual skeletal effects of ZOL after treatment discontinuation, or the continued length of therapy required for the prolonged protective benefits on BMD and BTMs. Sample sizes have been small, and studies were not adequately powered to evaluate fracture incidence. A single ZOL infusion has been shown to decrease BTMs and improve BMD for at least 12 months after infusion. Patients may experience continued benefit beyond this period, but there is concern that this long-term effect may lead to severe bone-turnover suppression, increased bone fragility, and increased risk of fractures. Additional extension studies should be conducted to determine the long-term effects of discontinuing ZOL therapy on bone health as well as the length of preserved bone strength after last administration.


Role of transcriptional regulation and enzyme inactivation in the synthesis of Escherichia coli carbamoylphosphate synthase.
The question of posttranscriptional control during cumulative repression of Escherichia coli carbamoylphosphate synthase has been examined by following the kinetics of repression and by comparing messenger ribonucleic acid and enzyme levels after growth under various conditions. The data provide no evidence for control of synthesis at a level other than transcription. They suggest, however, that enzyme inactivation (or turnover) plays a significant role in the establishment of repressive conditions.


Averaged implicit hydrodynamic model of semiflexible filaments.
We introduce a method to incorporate hydrodynamic interaction in a model of semiflexible filament dynamics. Hydrodynamic screening and other hydrodynamic interaction effects lead to nonuniform drag along even a rigid filament, and cause bending fluctuations in semiflexible filaments, in addition to the nonuniform Brownian forces. We develop our hydrodynamics model from a string-of-beads idealization of filaments, and capture hydrodynamic interaction by Stokes superposition of the solvent flow around beads. However, instead of the commonly used first-order Stokes superposition, we do an equivalent of infinite-order superposition by solving for the true relative velocity or hydrodynamic velocity of the beads implicitly. We also avoid the computational cost of the string-of-beads idealization by assuming a single normal, parallel and angular hydrodynamic velocity over sections of beads, excluding the beads at the filament ends. We do not include the end beads in the averaging and solve for them separately instead, in order to better resolve the drag profiles along the filament. A large part of the hydrodynamic drag is typically concentrated at the filament ends. The averaged implicit hydrodynamics methods can be easily incorporated into a string-of-rods idealization of semiflexible filaments that was developed earlier by the authors. The earlier model was used to solve the Brownian dynamics of semiflexible filaments, but without hydrodynamic interactions incorporated. We validate our current model at each stage of development, and reproduce experimental observations on the mean-squared displacement of fluctuating actin filaments . We also show how hydrodynamic interaction confines a fluctuating actin filament between two stationary lateral filaments. Finally, preliminary examinations suggest that a large part of the observed velocity in the interior segments of a fluctuating filament can be attributed to induced solvent flow or hydrodynamic screening.


Pain management in burn patients.
Despite advances, inappropriate analgesic treatment for burn patients is still seen. The objective of this review was to collect data on pain management in burn patients. We reviewed the mechanisms of pain, burn patient assessment, as well as pharmacological and non-pharmacological treatment. Pain management in burn patients is still a challenge for the multidisciplinary team. Frequent and continuous evaluation of the patient's response is very important due to the various stages that the hospitalized burn patient goes through, as well as a combination therapy with analgesic and non-pharmacological measures. Understanding the complexity of the pathophysiological, psychological, and biochemical changes a burn patient presents is the first step to achieve success in analgesic management.


Endobronchial metastasis of mixed germ cell tumors: two cases.
Lung metastases from extrapulmonary malignancies are common however endobronchial metastases (EBM) from nonpulmonary neoplasms are rare. A variety of extrathoracic tumors have a tendency to EBM especially breast, colon, and renal carcinomas are most frequent reported tumors however EBM of germ cell tumors are extremely rare. A 39-year-old and a 27-year-old male patient were admitted to our hospital with hemoptysis and dyspnea at different times. Both of them had a history of left orchiectomy due to mixed germ cell tumor two years and one year ago, respectively. On chest X-Ray and thorax computed tomography, first had a right upper lobe atelectasis and second had right total atelectasis. Fiberoptic bronchoscopy (FOB) performed and a vascularized endobronchial lesion (EBL) which tended to bleed was seen in the orifis of right upper lobe in the first case and right main bronchus was totally obstructed by EBL also in the second. Interventional bronchoscopy was performed via rigid bronchoscopy for biopsy and palliative treatment (argon plasma coagulation and debulking) in both two patients because of tendency to bleeding. A partial aperture was achieved at right upper lobe bronchus in the first case and total atelectasis resolved in the second case. Immunohistochemically, histopathological examinations of both patients biopsies confirmed EBM of mixed germ cell tumors. In conclusion, EBM of the germ cell tumors especially with total or partial atelectasis are extremely rare. We want to present these cases to emphasize the importance of distinguishing EBM from primary lung carcinoma which treatment and survival could be different.


[Chest pain in children: a practical approach].
Chest pain presenting during childhood is a common cause of admission to the emergency departments or to pediatric outpatient consultations. In most cases chest pain is idiopathic or secondary to musculoskeletal disorders, whereas a cardiac origin is confirmed in a minority (0.5-1%). The peak of incidence can be registered between 10-14 years, mainly involving males. Early identification of chest pain requiring further investigation allows a prompt diagnosis, limiting unnecessary exams and prolonged hospitalization.


Exploring Australian speech-language pathologists' use and perceptions ofnon-speech oral motor exercises.
To explore Australian speech-language pathologists' use of non-speech oral motor exercises, and rationales for using/not using non-speech oral motor exercises in clinical practice. A total of 124 speech-language pathologists practising in Australia, working with paediatric and/or adult clients with speech sound difficulties, completed an online survey. The majority of speech-language pathologists reported that they did not use non-speech oral motor exercises when working with paediatric or adult clients with speech sound difficulties. However, more than half of the speech-language pathologists working with adult clients who have dysarthria reported using non-speech oral motor exercises with this population. The most frequently reported rationale for using non-speech oral motor exercises in speech sound difficulty management was to improve awareness/placement of articulators. The majority of speech-language pathologists agreed there is no clear clinical or research evidence base to support non-speech oral motor exercise use with clients who have speech sound difficulties. This study provides an overview of Australian speech-language pathologists' reported use and perceptions of non-speech oral motor exercises' applicability and efficacy in treating paediatric and adult clients who have speech sound difficulties. The research findings provide speech-language pathologists with insight into how and why non-speech oral motor exercises are currently used, and adds to the knowledge base regarding Australian speech-language pathology practice of non-speech oral motor exercises in the treatment of speech sound difficulties. Implications for Rehabilitation Non-speech oral motor exercises refer to oral motor activities which do not involve speech, but involve the manipulation or stimulation of oral structures including the lips, tongue, jaw, and soft palate. Non-speech oral motor exercises are intended to improve the function (e.g., movement, strength) of oral structures. The majority of speech-language pathologists agreed there is no clear clinical or research evidence base to support non-speech oral motor exercise use with clients who have speech sound disorders. Non-speech oral motor exercise use was most frequently reported in the treatment of dysarthria. Non-speech oral motor exercise use when targeting speech sound disorders is not widely endorsed in the literature.


Efficacy of 190 mcg fluocinolone acetonide intravitreal implant: microperimetry and OCT real-life data.
Fluocinolone acetonide is a valid alternative treatment for patients with chronic diabetic macular edema (DME) with poor response to anti-vascular endothelial growth factor (VEGF) therapy. The purpose of this study is to report the efficacy and safety of ILUVIEN® implant in pseudophakic eyes with persistent DME. This is a single-centre pilot-study of 8 patients with persistent DME treated with the ILUVIEN implant, despite previous anti-vascular endothelial growth factor and/or steroid treatment. Best-corrected visual acuity (BCVA), optical coherence tomography (OCT) central retinal thickness, intraocular pressure (IOP) and microperimetric data were evaluated at baseline and month 1, 3 and 6 post treatment. All data are presented as mean and standard deviation. At baseline, 1, 3 and 6 months, we had BCVA of 0.26±0.22, 0.38±0.27, 0.48±0.27 and 0.46±0.24; IOP of 15.00±2.67, 15.50±3.16, 14.88±2.42 and 15.63±2.67 mmHg; macular thickness of 652±231, 487±278, 475±287 and 413±211 µm; macular sensitivity of 6.83±4.20, 6.13±3.72, 7.68±3.40 and 7.71±3.33 dB; bivariate contour elliptic area (BCEA) 95.4% 3.8±3.42, 6.06±10.06, 3.05±2.46 and 2.59±2.19°2. According to the results of our study, fluocinolone acetonide (FAc) is a valid therapy option despite some limitations. It has been evidenced that FAc is more effective in patients with mild central macular thickening, while in those with modest to severe central macular thickness (CMT), different therapy strategies should be considered.


IgA nephropathy in a patient with ankylosing spondylitis and a solitary kidney.
We describe a patient with ankylosing spondylitis and psoriasis who was found to have IgA nephropathy in a solitary kidney. Renal biopsy demonstrated mesangial proliferation and interstitial nephritis with mesangial deposition of IgA. Although the renal disease and the rheumatic disease could have been present together by chance association, evidence is presented to suggest a possible common pathogenesis.


A model for demonstration of reversal of impairment of endothelium-dependent relaxation in the cholesterol-fed rabbit.
This investigation was undertaken to determine whether it was possible to restore endothelium-dependent relaxation (EDR) in the cholesterol-fed rabbit model of atherosclerosis following discontinuation of the cholesterol. New Zealand white rabbits, approximately 8 weeks of age, were randomized into (i) control group (9 animals fed a standard rabbit diet) and (ii) experimental group (27 animals: fed the same diet supplemented with 2.5% cholesterol). The experimental animals were restored to the standard diet after 3 weeks. EDR to acetylcholine (-9.0 to -5.0 log mol/L) was examined in the experimental animals at 3, 7, and 15 weeks after commencement of the study (n = 9 at each stage) and the nine control animals examined after 7 weeks. At the end of 7 weeks, EDR to acetylcholine (-6.0 log mol/L) was significantly (p less than 0.05) impaired in the experimental group (34.3 +/- 3.8%) compared with that in the control group (79.8 +/- 3.0%). The loss of EDR was not apparent in the experimental group at 3 weeks (relaxation: 81.7 +/- 4.7%). At the end of 15 weeks, the EDR was significantly restored in the experimental group (relaxation: 63.6 +/- 5.1%). These findings demonstrate that it is possible to reverse the loss of EDR that occurs with cholesterol feeding in the rabbit by limiting the period of exposure to a high cholesterol diet.


Longitudinal measurement invariance in prospective oral health-related quality of life assessment.
Prospective assessments of oral health-related quality of life (OHRQoL) changes are prone to response shift effects when patients reconceptualize, reprioritize, or recalibrate the perceived meanings of OHRQoL test items. If this occurs, OHRQoL measurements are not "invariant" and may reflect changes in problem profiles or perceptions of OHRQoL test items. This suggests that response shift effects must be measured and controlled to achieve valid prospective OHRQoL measurement. The aim of this study was to quantify response shift effects of Oral Health Impact Profile (OHIP) scores in prospective studies of prosthodontic patients. Data came from the Dimensions of Oral Health-Related Quality of Life Project. The final sample included 554 patients who completed the OHIP questionnaire on two occasions: pre- and post-treatment. Only items that compose the 14-item OHIP were analyzed. Structural equation models that included pre- and post-treatment latent factors of OHRQoL with different across-occasion constraints for factor loadings, intercepts, and residual variances were fit to the data using confirmatory factor analysis. Data fit both the unconstrained model (RMSEA = .038, SRMR = .051, CFI = .92, TLI = .91) and the partially constrained model with freed residual variances (RMSEA = .037, SRMR = .064, CFI = .92, TLI = .92) well, meaning that the data are well approximated by a one-factor model at each occasion, and suggesting strong factorial across-occasion measurement invariance. The results provided cogent evidence for the absence of response shift in single factor OHIP models, indicating that longitudinal OHIP assessments of OHRQoL measure similar constructs across occasions.


Association of a (TTTA)n microsatellite and a TCT del/ins polymorphisms in the aromatase gene (CYP19) with hip fracture risk in Mexican postmenopausal women.
A (TTTA)n polymorphism in the aromatase gene has been studied in relation to bone mineral density (BMD). The low number of TTTA repeats has been associated with low BMD and fracture risk. The aim of this study was to search for associations of TTTA copy number with hip fracture and lumbar spine osteoporosis in Mexican peri and postmenopausal women. The allele with seven repeats was present in the two reported versions, with or without a TCT deletion upstream of the microsatellite (A1 and A2, respectively). After adjustment by confounders, the A1 allele and the A1A1 genotype were significantly associated with an elevated risk of fracture (p = 0.034, OR = 3.2 [95% CI, 1.09-9.41] and p = 0.019, OR = 2.26 [95% CI, 1.14-4.49], respectively) and the A2 allele was associated with protection of hip fracture (p = 0.04, OR = 0.48, [95% CI, 0.22-1.05]) as the A2A2 genotype (p = 0.048, OR = 0.29 [95% CI, 0.06-1.16]). The analysis allowed us to defining the usefulness of the (TTTA)n polymorphism in the aromatase gene as an indicator of hip fracture risk in Mexican population.


Exploring Phylogeographic Congruence in a Continental Island System.
A prediction in phylogeographic studies is that patterns of lineage diversity and timing will be similar within the same landscape under the assumption that these lineages have responded to past environmental changes in comparable ways. Eight invertebrate taxa from four different orders were included in this study of mainland New Zealand and Chatham Islands lineages to explore outcomes of island colonization. These comprised two orthopteran genera, one an endemic forest-dwelling genus of cave weta (Rhaphidophoridae, Talitropsis) and the other a grasshopper (Acrididae, Phaulacridum) that inhabits open grassland; four genera of Coleoptera including carabid beetles (Mecodema), stag beetles (Geodorcus), weevils (Hadramphus) and clickbeetles (Amychus); the widespread earwig genus Anisolabis (Dermaptera) that is common on beaches in New Zealand and the Chatham Islands, and an endemic and widespread cockroach genus Celatoblatta (Blattodea). Mitochondrial DNA data were used to reconstruct phylogeographic hypotheses to compare among these taxa. Strikingly, despite a maximum age of the Chathams of ~4 million years there is no concordance among these taxa, in the extent of genetic divergence and partitioning between Chatham and Mainland populations. Some Chatham lineages are represented by insular endemics and others by haplotypes shared with mainland populations. These diverse patterns suggest that combinations of intrinsic (taxon ecology) and extrinsic (extinction and dispersal) factors can result in apparently very different biogeographic outcomes.


Quantitation of metabolites of the nerve agents sarin, soman, cyclohexylsarin, VX, and Russian VX in human urine using isotope-dilution gas chromatography-tandem mass spectrometry.
Organophosphorus nerve agents are among the most toxic organic compounds known and continue to be a threat for both military and terrorist use. We have developed an isotope-dilution gas chromatography-tandem mass spectrometric (GC-MS-MS) method for quantitating the urinary metabolites of the organophosphorus nerve agents sarin (GB), soman (GD), VX, Russian VX (RVX), and cyclohexylsarin (GF). Urine samples were acidified, extracted into ether-acetonitrile, derivatized by methylation with diazomethane, and analyzed by GC-MS-MS. The limits of detection were less than 1 micro g/L for all analytes.


Effect of a small molecule Lipid II binder on bacterial cell wall stress.
We have recently identified small molecule compounds that act as binders of Lipid II, an essential precursor of bacterial cell wall biosynthesis. Lipid II comprised a hydrophilic head group that includes a peptidoglycan subunit composed of N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) coupled to a short pentapeptide moiety. This headgroup is coupled to a long bactoprenol chain via a pyrophosphate group. Here, we report on the cell wall activity relationship of dimethyl-3-methyl(phenyl)amino-ethenylcyclohexylidene-propenyl-3-ethyl-1,3-benzothiazolium iodide (compound 5107930) obtained by functional and genetic analyses. Our results indicate that compounds bind to Lipid II and cause specific upregulation of the vancomycin-resistance associated gene vraX. vraX is implicated in the cell wall stress stimulon that confers glycopeptide resistance. Our small molecule Lipid II inhibitor retained activity against strains of Staphylococcus aureus mutated in genes encoding the cell wall stress stimulon. This suggests the feasibility of developing this new scaffold as a therapeutic agent in view of increasing glycopeptide resistance.


[Usefulness of echography in the diagnosis of intestinal intussusception].
The usefulness of echography in the diagnosis and tracing down of an intestinal intussusception is discussed. An abdominal ecograph was done in 29 children with suspected intestinal intussusception. In 31 cases (63%) the diagnosis was confirmed by the typical "target" image. In 17 cases (34%) the picture of intussusception was not detected, all children evolved favourably except for one case which, upon revision of the ecograph, showed the "target" picture not properly interpreted in the first place. We find the abdominal ecograph a useful means for diagnosis of intestinal intussusception. We present the diagnostic-therapeutic routine in our centre in cases of possible intestinal intussusception.


Bosom buddies.
Exclusive breastfeeding for the first six months gives babies the best possible start in life, but only 2 per cent of UK women achieve this goal.


[Efficacy of monotherapy with 15 antihypertensive agents in treating essential hypertension assessed by 24-hour ambulatory blood pressure monitoring].
To evaluate the efficacy of the monotherapy of 15 agents in treating essential hypertension. After 2-week wash-out, a total of 370 patients with seated diastolic blood pressure 95-114 mmHg and seated systolic blood pressure < 180 mmHg were randomized to different therapeutic groups. 24-hour ambulatory blood pressure monitoring was performed before medication and at the end of 8 weeks. All the agents significantly reduced the 24 hour mean blood pressures after treatment except doxazosin, terazosin, and torasemide. The result suggested that the angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers and long-acting calcium antagonists were effective in treating essential hypertension, while the low-dose doxazosin, terazosin and torasemide can be used for combination therapy but not for monotherapy.


[Prognostic significance of diabetes in a heart failure population: one year mortality and heart failure related hospital admission].
The relationship between diabetes mellitus and heart failure is not fully established. The aim of the study was to assess the prevalence of diabetes and its prognostic significance, considering mortality and the need of hospital admission due to heart failure during the first year of follow-up, in an outpatient population with heart failure attended in a specialized Unit. We studied 362 patients -73% men; mean age (standard deviation) 65.3 (10.9) years-. Mean ejection fraction was 32.2% (12.7%). Patients were in New York Heart Association functional class I (5%), II (47%), III (43%) and IV (5%). One-hundred forty-three out of 362 patients were diabetic (39.5%). Thirty patients (8%) died and 70 (19%) needed to be hospitalized due to heart failure during the first year of follow-up. One year mortality was 5% in non-diabetic patients and 13.3% in diabetic patients (p = 0.005). 13.2% of non-diabetic patients suffered at least one episode of heart failure needing hospital admission, whereas 28.7% of diabetic patients needed to be hospitalized at least once (p < 0.001). In the multivariate regression analysis, diabetes remained statistically associated both with mortality and with the need of heart failure related hospital admission. Diabetes significantly correlated with a higher one year mortality as well as with a greater need of hospital admission due to heart failure. Prevalence of diabetes in a general population with heart failure was high.


Seroprevalence of Human Immunodeficiency Virus, Hepatitis B, Hepatitis C, Syphilis, and Co-infections among Antenatal Women in a Tertiary Institution in South East, Nigeria.
Sexually transmitted infections and human immunodeficiency virus (HIV)/AIDS are a major public health concern owing to both their prevalence and propensity to affect offspring through vertical transmission. The aim was to determine the seroprevalence of HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis, and co-infections among antenatal women in Enugu, South-East Nigeria. A retrospective study of antenatal women at the University of Nigeria Teaching Hospital, Enugu, South-East Nigeria from 1(st) May 2006 to 30(th) April 2008. A pretested data extraction form was used to obtain data on sociodemographic variables and screening test results from the antenatal records. The analysis was done with SPSS version 17 (Chicago, IL, USA). A total of 1239 antenatal records was used for the study. The seroprevalence of HIV, HBV, HCV, and syphilis among the antenatal women were 12.4% (154/1239), 3.4% (42/1239) 2.6 (32/1239) 0.08% (1/1239), respectively. The HIV/HBV and HIV/HCV co-infection prevalence rates were 0.24% (3/1239), 0.16% (2/1239), respectively. There was no HBC and HCV co-infection among both HIV positive and negative antenatal women. There was no statistically significant difference in HBV and HCV infection between the HIV positive and negative antenatal women. The only woman that was seropositive for syphilis was also positive to HIV. The seroprevalence of HIV, HBV, HCV, and syphilis is still a challenge in Enugu. Community health education is necessary to reduce the prevalence of this infection among the most productive and economically viable age bracket.


Histopathological examination of appendicectomy specimens at a district hospital of Saudi Arabia.
Appendicectomy for acute appendicitis is one of the most commonly performed surgical procedures. Acute appendicitis has remained a clinical entity and an ongoing diagnostic challenge. A retrospective study was performed to determine histological diagnosis, demographic data, the rate of perforated appendicitis and negative appendicectomies. Histopathological records of 480 resected appendices submitted to histopathology department at Arar Central Hospital in the Northern Border Province of Saudi Arabia over the period of 3 years from July 2011 to June 2014 were reviewed retrospectively, to determine acute appendicitis, complication (gangrene, perforation) rate, negative appendicectomy rate, histopathological diagnosis and unusual finding on histology. Out of 480 specimens of appendix, appendicitis accounted for 466 (97.0%) with peak occurrence in the age group of 11 to 50 years in male and 11 to 40 years in female. Histopathological diagnosis include acute appendicitis 250 (52.0%), suppurative appendicitis 135 (28.0%) acute gangrenous appendicitis 60 (12.5%), perforated appendicitis 9 (2.0%), chronic appendicitis 12 (2.5%). Negative appendicectomy rate was 14 (3%) and two time more common in female with peak occurrence in the age group of 20-30 yrs. There was no unusual histological finding like carcinoid tumour of appendix. The present study showed a high number of appendicitis in adolescents and young adults. Negative appendectomy was more common in females. The study support routine histological examination of all the appendicectomy specimens to avoid missing of any clinically important and treatable condition.