Blockade of opioid receptors in rostral ventral medulla prevents antihyperalgesia produced by transcutaneous electrical nerve stimulation (TENS).
Although transcutaneous electrical nerve stimulation (TENS) is used extensively in inflammatory joint conditions such as arthritis, the underlying mechanisms are unclear. This study aims to demonstrate an opiate-mediated activation of descending inhibitory pathways from the rostral ventral medulla (RVM) in the antihyperalgesia produced by low- (4 Hz) or high-frequency (100 Hz) TENS. Paw withdrawal latency to radiant heat, as an index of secondary hyperalgesia, was recorded before and after knee joint inflammation (induced by intra-articular injection of 3% kaolin and carrageenan) and after TENS/no TENS coadministered with naloxone (20 microg/1 microl), naltrindole (5 microg/1 microl), or vehicle (1 microl) microinjected into the RVM. The selectivity of naloxone and naltrindole doses was tested against the mu-opioid receptor agonist [D-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin (DAMGO) (20 ng, 1 microl) and the delta2-opioid receptor agonist deltorphin (5 microg, 1 microl) in the RVM. Naloxone microinjection into the RVM blocks the antihyperalgesia produced by low frequency (p < 0.001), but not that produced by high-frequency TENS (p > 0.05). In contrast, naltrindole injection into the RVM blocks the antihyperalgesia produced by high-frequency (p < 0.05), but not low-frequency (p > 0.05) TENS. The analgesia produced by DAMGO and deltorphin is selectively blocked by naloxone (p < 0.05) and naltrindole (p < 0.05), respectively. Thus, the dose of naloxone and naltrindole used in the current study blocks mu- and delta-opioid receptors, respectively. Hence, low-frequency and high-frequency TENS produces antihyperalgesia by activation of mu- and delta-opioid receptors, respectively, in the RVM.


Why urban citizens in developing countries use traditional medicines: the case of suriname.
The use of traditional medicines (TMs) among urban populations in developing countries and factors underlying people's decision to use TMs are poorly documented. We interviewed 270 adults in Paramaribo, Suriname, using a stratified random household sample, semistructured questionnaires, and multivariate analysis. Respondents mentioned 144 medicinal plant species, most frequently Gossypium barbadense, Phyllanthus amarus, and Quassia amara. 66% had used TMs in the previous year, especially people who suffered from cold, fever, hypertension, headache, uterus, and urinary tract problems. At least 22% combined herbs with prescription medicine. The strongest explanatory variables were health status, (transfer of) plant knowledge, and health status combined with plant knowledge. Other predictive variables included religion, marital status, attitude of medical personnel, religious opinion on TMs, and number of children per household. Age, gender, nationality, rural background, education, employment, income, insurance, and opinion of government or doctors had no influence. People's main motivation to use TMs was their familiarity with herbs. Given the frequent use of self-collected, home-prepared herbal medicine and the fact that illness and traditional knowledge predict plant use rather than poverty or a limited access to modern health care, the potential risks and benefits of TMs should be put prominently on the national public health agenda.


Sequential protocol biopsies from renal transplant recipients show an increasing expression of active TGF beta.
Chronic allograft nephropathy (CAN) is a major cause of graft loss after renal transplantation. Implicated in the pathogenesis of this complication is overproduction of the cytokine transforming growth factor beta (TGF beta). In this study we measured changes in CAN's expression in stable patients early after transplantation, and studied links with established risk factors for CAN, such as delayed graft function, acute rejection, and cyclosporine exposure. We took biopsies from 40 renal allografts at time of transplantation (pre-perfusion), and then, using ultrasound guidance, at 1 week and 6 months after transplantation. An immunofluorescence technique was used to stain sections for active TGF beta. These were then assessed by semi-quantitative scanning laser confocal microscopy. There was very little variation in active TGF-beta expression among patients in their pre-perfusion biopsies. Expression had increased by 1 week and then very significantly by 6 months ( P<0.0001). Patients who suffered delayed graft function had increased TGF-beta expression at both time points. There was no difference regarding donor type, acute rejection, and immunosuppressive drug (cyclosporine or tacrolimus). There was no correlation between the amount of TGF-beta expression at any time-point and isotope glomerular filtration rate (GFR) at 12 months. This study demonstrated that in a group of stable renal allograft recipients, TGF-beta expression in the kidney increased after transplantation. As the study used protocol biopsies, this increase is unlikely to be due to acute events, and probably represents a genuine increase.


Theory and Evidence for Platelet Therapy of the Aging Face.
Platelet preparations are autologous blood concentrates with supraphysiologic concentrations of platelets with or without leukocytes used in various clinical applications including regenerative medicine, wound healing, and facial rejuvenation. Their use harnesses the important role of platelets and their secretory products in immunoregulation, wound healing, angiogenesis, and tissue remodeling. The use of platelet preparations has been long documented in orthopaedic surgery, maxillofacial surgery, and other fields, but over the years research has increased in their application to facial plastic surgical techniques. Here we review the various formulations of platelet rich concentrates, their applications to facial skin rejuvenation, wound healing, scar reduction, and tissue fill as documented in the literature since 2018.


Challenges and Opportunities of System-Level Prognostics.
Prognostics and health management (PHM) has become an essential function for safe system operation and scheduling economic maintenance. To date, there has been much research and publications on component-level prognostics. In practice, however, most industrial systems consist of multiple components that are interlinked. This paper aims to provide a review of approaches for system-level prognostics. To achieve this goal, the approaches are grouped into four categories: health index-based, component RUL-based, influenced component-based, and multiple failure mode-based prognostics. Issues of each approach are presented in terms of the target systems and employed algorithms. Two examples of PHM datasets are used to demonstrate how the system-level prognostics should be conducted. Challenges for practical system-level prognostics are also addressed.


Reversible interconversion of CO2 and formate by a molybdenum-containing formate dehydrogenase.
CO2 and formate are rapidly, selectively, and efficiently interconverted by tungsten-containing formate dehydrogenases that surpass current synthetic catalysts. However, their mechanism of catalysis is unknown, and no tractable system is available for study. Here, we describe the catalytic properties of the molybdenum-containing formate dehydrogenase H from the model organism Escherichia coli (EcFDH-H). We use protein film voltammetry to demonstrate that EcFDH-H is a highly active, reversible electrocatalyst. In each voltammogram a single point of zero net current denotes the CO2 reduction potential that varies with pH according to the Nernst equation. By quantifying formate production we show that electrocatalytic CO2 reduction is specific. Our results reveal the capabilities of a Mo-containing catalyst for reversible CO2 reduction and establish EcFDH-H as an attractive model system for mechanistic investigations and a template for the development of synthetic catalysts.


Lethal arrhythmias in Tbx3-deficient mice reveal extreme dosage sensitivity of cardiac conduction system function and homeostasis.
TBX3 is critical for human development: mutations in TBX3 cause congenital anomalies in patients with ulnar-mammary syndrome. Data from mice and humans suggest multiple roles for Tbx3 in development and function of the cardiac conduction system. The mechanisms underlying the functional development, maturation, and maintenance of the conduction system are not well understood. We tested the requirements for Tbx3 in these processes. We generated a unique series of Tbx3 hypomorphic and conditional mouse mutants with varying levels and locations of Tbx3 activity within the heart, and developed techniques for evaluating in vivo embryonic conduction system function. Disruption of Tbx3 function in different regions of the developing heart causes discrete phenotypes and lethal arrhythmias: sinus pauses and bradycardia indicate sinoatrial node dysfunction, whereas preexcitation and atrioventricular block reveal abnormalities in the atrioventricular junction. Surviving Tbx3 mutants are at increased risk for sudden death. Arrhythmias induced by knockdown of Tbx3 in adults reveal its requirement for conduction system homeostasis. Arrhythmias in Tbx3-deficient embryos are accompanied by disrupted expression of multiple ion channels despite preserved expression of previously described conduction system markers. These findings indicate that Tbx3 is required for the conduction system to establish and maintain its correct molecular identity and functional properties. In conclusion, Tbx3 is required for the functional development, maturation, and homeostasis of the conduction system in a highly dosage-sensitive manner. TBX3 and its regulatory targets merit investigation as candidates for human arrhythmias.


Cisplatin nephrotoxicity is critically mediated via the human organic cation transporter 2.
Cis-platin is an effective anti-neoplastic agent, but it is also highly nephrotoxic. Here, we clearly identify the human organic cation transporter 2 (hOCT2) as the critical transporter for cis-platin nephrotoxicity in isolated human proximal tubules and offer a potential mechanism for reducing nephrotoxicity in clinical practice. Interaction of cis-platin with hOCT2 in kidney or hOCT1 in liver was investigated with the fluorescent cation 4-[4-(dimethyl-amino)styril]-methylpyridinium in stably transfected HEK293 cells and for the first time in tissues physiologically expressing these transporters, human proximal tubules, and human hepatocyte couplets. Cis-platin (100 micromol/L) inhibited transport via hOCT2-HEK293 but not hOCT1-HEK293. In human proximal tubules cis-platin competed with basolateral organic cation transport, whereas it had no effect in tubules from a diabetic kidney or in hepatocytes. In hOCT2-HEK293 cells treated for 15 hours, incubation with cis-platin induced apoptosis, which was completely suppressed by contemporaneous incubation with the hOCT2 substrate cimetidine (100 micromol/L). These findings demonstrate that uptake of cis-platin is mediated by hOCT2 in renal proximal tubules, explaining its organ-specific toxicity. A combination of cis-platin with other substrates that compete for hOCT2 offers an effective option to decrease nephrotoxicity in the clinical setting.


Influence of Mass Resolving Power in Orbital Ion-Trap Mass Spectrometry-Based Metabolomics.
Modern separation methods in conjunction with high-resolution accurate mass (HRAM) spectrometry can provide an enormous number of features characterized by exact mass and chromatographic behavior. Higher mass resolving power usually requires longer scanning times, and thus fewer data points are acquired across the target peak. This could cause difficulties for quantification, feature detection and deconvolution. The aim of this work was to describe the influence of mass spectrometry resolving power on profiling metabolomics experiments. From metabolic databases (HMDB, LipidMaps, KEGG), a list of compounds (41 474) was compiled and potential adducts and isotopes were calculated (622 110 features). The number of distinguishable masses was calculated for up to 3840k resolution. To evaluate these models, human plasma samples were analyzed by LC-HRMS on an Orbitrap Elite hybrid mass spectrometer (Thermo Fisher Scientific, CA, USA) at resolving power settings of 15k (7.8 Hz) up to a maximum of 480k (1.2 Hz). Software XCMS 1.44, MZmine 2.13.1, and Compound Discoverer 126.96.36.1993 were used for evaluation. In plasma samples, the number of detected features increased sharply up to 60k in both positive and negative mode. However, beyond these values, it either flattened out or decreased owing to technical limitations. In conclusion, the most effective mass resolving powers for profiling analyses of metabolite rich biofluids on the Orbitrap Elite were around 60 000-120 000 fwhm to retrieve the highest amount of information. The region between 400-800 m/z was influenced the most by resolution.


A comparison of coping factors in Western and non-Western cultures.
This study presents convergent support for the use of three empirically constructed factors, across four samples, from the Ways of Coping Questionnaire. Planning, Positive Reappraisal, and Distancing factors were congruent for comparisons made between U.S. healthcare workers, Chinese healthcare workers, Chinese teachers, and Taiwanese teachers. Additional evidence of congruency was provided on specific factors between specific pairs of groups. The results support the usage of common factors across languages, cultures, and occupational groups but also highlight the importance of not administering a test in a different cultural setting without assessing its dimensionality.


A validated method for analysis of chromium picolinate in nutraceuticals by reversed phase high performance liquid chromatography.
A validated high performance liquid chromatographic method was developed for the determination of chromium picolinate in pharmaceutical dosage forms. The analysis was performed at room temperature using a reversed-phase Supelcosil LC-18 (250 x 4.6 mm, 5 microm) column. The mobile phase consisted of acetonitrile:water (40:60 v/v) at a fl ow rate of 0.8 mL/min. The UV-detector was set at 264 nm. The developed method showed a good linear relationship in the concentration range from 0.125 to 12.5 microg/mL with a correlation coefficient from 0.999. The limit of detection and limit of quanti fi cation were 0.091 and 0.181 microg/mL, respectively.


Comparison of substrate specificity among human arylacetamide deacetylase and carboxylesterases.
Human arylacetamide deacetylase (AADAC) is an esterase responsible for the hydrolysis of some drugs, including flutamide, indiplon, phenacetin, and rifamycins. AADAC is highly expressed in the human liver, where carboxylesterase (CES) enzymes, namely, CES1 and CES2, are also expressed. It is generally recognized that CES1 prefers compounds with a large acyl moiety and a small alcohol or amine moiety as substrates, whereas CES2 prefers compounds with a small acyl moiety and a large alcohol or amine moiety. In a comparison of the chemical structures of known AADAC substrates, AADAC most likely prefers compounds with the same characteristics as does CES2. However, the substrate specificity of human AADAC has not been fully clarified. To expand the knowledge of substrates of human AADAC, we measured its hydrolase activities toward 13 compounds, including known human CES1 and CES2 substrates, using recombinant enzymes expressed in Sf21 cells. Recombinant AADAC catalyzed the hydrolysis of fluorescein diacetate, N-monoacetyldapsone, and propanil, which possess notably small acyl moieties, and these substrates were also hydrolyzed by CES2. However, AADAC could not hydrolyze another CES2 substrate, procaine, which possesses a moderately small acyl moiety. In addition, AADAC did not hydrolyze several known CES1 substrates, including clopidogrel and oseltamivir, which have large acyl moieties and small alcohol moieties. Collectively, these results suggest that AADAC prefers compounds with smaller acyl moieties than does CES2. The role of AADAC in the hydrolysis of drugs has been clarified. For this reason, AADAC should receive attention in ADMET studies during drug development.


Long-term nationwide trends in the treatment of and outcomes among pancreatic cancer patients.
Whilst treatment modalities for pancreatic cancer patients have evolved in recent years, their impact on outcomes remains relatively unexamined on a national scale. We aimed to analyse changes in overall survival and trends in surgical and oncological treatments in pancreatic cancer patients diagnosed in the periods 2000 through 2008 and 2009 through 2016 in Finland. We collected data for pancreatic cancer patients diagnosed between 2000 and 2016, gathering data from the Finnish national registries on surgeries, oncological treatments and time of death. Follow-up continued through the end of 2018. We compared patients diagnosed between 2000 and 2008 to those diagnosed between 2009 through 2016. Our study comprised 14 712 pancreatic cancer patients. There was no significant change in the national resection rate (8.1% vs 8.0%, p = 0.690). In radical surgery patients, median survival improved from 20 months (95% confidence interval (CI) 18-22) to 28 months (CI 25-31) (p < 0.001), with 1-year survival ranging from 70% to 81%. In the no-surgery group, median survival slightly improved from 3.1 months (CI 3.0-3.3) to 3.3 months (CI 3.1-3.4) (p < 0.001). The proportion of radical surgery patients receiving preoperative oncological treatment increased from 4% to 13% (p < 0.001) and only postoperative treatment from 25% to 47% (p < 0.001). Whilst the resection rate did not increase, the prognosis of pancreatic cancer patients improved, particularly amongst radical surgery patients resulting most likely from the fact that a larger proportion of patients receive more effective oncological treatments.


[Cervical seminoma. Presentation of a case].
A germinal cells tumor in a male manifested as left supraclavicular mass, without other localisation, is presented. The pathologic anatomy corroborate the diagnosis of seminoma. Very few cases of a germinal cell tumor in the supraclavicular fossa, with a normal testicular exploration, have been reported.


Rhabdomyolysis and compartment syndrome in a bodybuilder undergoing minimally invasive cardiac surgery.
Rhabdomyolysis is the result of skeletal muscle tissue injury and is characterized by elevated creatine kinase levels, muscle pain, and myoglobinuria. It is caused by crush injuries, hyperthermia, drugs, toxins, and abnormal metabolic states. This is often difficult to diagnose perioperatively and can result in renal failure and compartment syndrome if not promptly treated. We report a rare case of inadvertent rhabdomyolysis and compartment syndrome in a bodybuilder undergoing minimally invasive cardiac surgery. The presentation, differential diagnoses, and management are discussed. Hyperkalemia may be the first presenting sign. Early recognition and management are essential to prevent life-threatening complications.


Unprotected vinyl aziridines: facile synthesis and cascade transformations.
Functionalized vinylaziridines, readily available from water-stable aziridine aldehydes have led to the construction of a variety of stereochemically rich heterobicycles. A cascade ring-opening/ring-contraction mechanism operates in the course of the process. These results underscore the notion that interesting and useful nitrogen-mediated relay processes can arise when elements of strain are merged with the manifolds of enamine/iminium ion reactivity.


Mycophenolate mofetil ameliorates perivascular T lymphocyte inflammation and reduces the double-negative T cell population in SLE-prone MRLlpr/lpr mice.
Effects on T lymphocyte mediated pathology, phenotypes, and functions in MRLlpr/lpr mice given mycophenolate mofetil (MMF) (100 mg/kg/day) via drinking water or controls given ip cyclophosphamide (CYC) injections (1.8 mg/mouse/week) or water were described. Both MMF and CYC treatment diminished kidney and large salivary gland perivascular cell infiltrates, reduced profoundly double-negative (DN) T cell frequencies, decreased total lymphocyte number in spleen, and increased in vitro proliferative response to Con A. IFN-gamma and IL-10 in supernatants from Con A stimulated spleen cells were augmented after MMF but not CYC treatment. MMF treatment increased whereas CYC reduced IL-12 in serum. Kidney expressions of IFN-gamma, IL-10, and IL-12 mRNA were unaffected by MMF but decreased by CYC. Our results demonstrate that MMF and CYC suppress perivascular T lymphocyte inflammation by reducing the DN T cell population and by amelioration of T cell function. The varying cytokine patterns suggest different mechanisms of the two drugs.


Mechanical ventilation-induced air-space enlargement during experimental pneumonia in piglets.
Mechanical ventilation-induced air-space enlargement was investigated in a porcine model of multifocal pneumonia. Following the intrabronchial inoculation of Escherichia coli, 9 piglets (22 +/- 2 kg) were ventilated with a tidal volume (VT) of 15 ml/kg for 43 +/- 15 h. Five noninoculated piglets ventilated for 60 h with the same VT served as control animals. Following death, the lungs were fixed and lung morphometry was assessed. In inoculated animals, unventilated infected and normally ventilated noninfected pulmonary lobules coexisted. In normally ventilated lung regions (1) emphysema-like lesions were present, (2) mean alveolar area and mean linear intercept were significantly greater in inoculated than in control animals, and (3) the degree of alveolar distension correlated with the decrease in respiratory compliance. In unventilated lung areas (1) pseudocysts were frequent, (2) alveolar edema was rare, (3) bronchiolectasis was frequent, (4) mean bronchiolar area was greater in inoculated than in control animals, and (5) the degree of bronchiolar distension correlated with the increase in inspiratory plateau pressure. In conclusion, in piglets with severe bronchopneumonia, air-space enlargement rather than pulmonary edema was the major feature of mechanical ventilation-induced lung barotrauma and resembled lesions previously reported in critically ill patients ventilated using high inspiratory pressures.


Autoregressive moving average modeling for spectral parameter estimation from a multigradient echo chemical shift acquisition.
The authors investigated the performance of the iterative Steiglitz-McBride (SM) algorithm on an autoregressive moving average (ARMA) model of signals from a fast, sparsely sampled, multiecho, chemical shift imaging (CSI) acquisition using simulation, phantom, ex vivo, and in vivo experiments with a focus on its potential usage in magnetic resonance (MR)-guided interventions. The ARMA signal model facilitated a rapid calculation of the chemical shift, apparent spin-spin relaxation time (T2*), and complex amplitudes of a multipeak system from a limited number of echoes (< or equal 16). Numerical simulations of one- and two-peak systems were used to assess the accuracy and uncertainty in the calculated spectral parameters as a function of acquisition and tissue parameters. The measured uncertainties from simulation were compared to the theoretical Cramer-Rao lower bound (CRLB) for the acquisition. Measurements made in phantoms were used to validate the T2* estimates and to validate uncertainty estimates made from the CRLB. We demonstrated application to real-time MR-guided interventions ex vivo by using the technique to monitor a percutaneous ethanol injection into a bovine liver and in vivo to monitor a laser-induced thermal therapy treatment in a canine brain. Simulation results showed that the chemical shift and amplitude uncertainties reached their respective CRLB at a signal-to-noise ratio (SNR) > or =5 for echo train lengths (ETLs) > or =4 using a fixed echo spacing of 3.3 ms. T2* estimates from the signal model possessed higher uncertainties but reached the CRLB at larger SNRs and/or ETLs. Highly accurate estimates for the chemical shift (<0.01 ppm) and amplitude (<1.0%) were obtained with > or =4 echoes and for T2*(<1.0%) with > or =7 echoes. We conclude that, over a reasonable range of SNR, the SM algorithm is a robust estimator of spectral parameters from fast CSI acquisitions that acquire < or =16 echoes for one- and two-peak systems. Preliminary ex vivo and in vivo experiments corroborated the results from simulation experiments and further indicate the potential of this technique for MR-guided interventional procedures with high spatiotemporal resolution approximately 1.6 x 1.6 x 4 mm3 in < or =5 s.


A First-in-Human Study and Biomarker Analysis of NKTR-214, a Novel IL2Rβγ-Biased Cytokine, in Patients with Advanced or Metastatic Solid Tumors.
NKTR-214 (bempegaldesleukin) is a novel IL2 pathway agonist, designed to provide sustained signaling through heterodimeric IL2 receptor βγ to drive increased proliferation and activation of CD8+ T and natural killer cells without unwanted expansion of T regulatory cells (Treg) in the tumor microenvironment. In this first-in-human multicenter phase I study, NKTR-214 administered as an outpatient regimen was well tolerated and showed clinical activity including tumor shrinkage and durable disease stabilization in heavily pretreated patients. Immune activation and increased numbers of immune cells were observed in the periphery across all doses and cycles with no loss of NKTR-214 activity with repeated administration. On-treatment tumor biopsies demonstrated that NKTR-214 promoted immune cell increase with limited increase of Tregs. Transcriptional analysis of tumor biopsies showed that NKTR-214 engaged the IL2 receptor pathway and significantly increased genes associated with an effector phenotype. Based on safety and pharmacodynamic markers, the recommended phase II dose was determined to be 0.006 mg/kg every three weeks. SIGNIFICANCE: We believe that IL2- and IL2 pathway-targeted agents such as NKTR-214 are key components to an optimal immunotherapy treatment algorithm. Based on its biological activity and tolerability, NKTR-214 is being studied with approved immuno-oncology agents including checkpoint inhibitors.See related commentary by Sullivan, p. 694.This article is highlighted in the In This Issue feature, p. 681.


Protection by various deoxynucleosides against deoxyadenosine-induced DNA damage in adenosine deaminase-inactivated lymphocytes.
Adenosine deaminase deficiency is an inborn error resulting in immunodeficiency. The pathogenesis of the lymphopenia is not fully understood. Intracellular increases in dATP in the absence of deamination retard DNA repair in human resting lymphocytes and results in the slow accumulation of DNA strand breaks. We focused on the relationship between DNA damage and DNA precursor pools in cultures of deoxycoformycin-treated, ADA-inhibited resting lymphocytes. The addition of 10 microM deoxyadenosine led to a substantial number of DNA strand breaks within 12 h, breaks equivalent to those which occur with about 190 rad irradiation. Addition of any of the other deoxynucleosides used partially prevented this dAdo-induced DNA damage and promoted DNA repair. However, the preventive effects did not correlate inversely with intracellular dATP levels. Resting lymphocytes have very small dNTP pools. Treatment with dAdo slightly reduced dTTP and dCTP. Three kinds of deoxynucleosides, other than dAdo, restored or raised the corresponding dNTP level but the pool imbalance was only minimally corrected. Regarding the toxic effects of dAdo in ADA deficiency, not only dATP levels but also dNTP pool balance has a crucial role in the pathogenesis. Pool sizes of dTTP, dCTP, and possibly dGTP must be maintained at normal levels, if dAdo-induced DNA damage is to be avoided.


Polarized rat uterine epithelium in vitro: constitutive expression of estrogen-induced proteins.
The hormonal responsiveness of immature rat primary uterine epithelial (UE) cells, cultured in a serum-free, phenol red-free defined medium, was examined under conditions which allowed the UE cells to reestablish their polarized phenotype. In the absence of estradiol and phenol red UE cells proliferated to confluence, achieving cell densities equal to those reached by UE cells cultured in the presence of estradiol. The expression of marker proteins, characteristic of the in vivo response of the uterus to estrogen, i.e. the adhesion molecule cell CAM 105, complement component C3, the secretory component of the immunoglobulin A receptor, and keratan sulfate proteoglycan, by polarized cultures of UE cells proved to be independent of estrogen in vitro. Polarized UE cells required the presence of estrogen to maintain integrity of their monolayer and did exhibit a dose-dependent response to estradiol in vitro in terms of cell growth (hypertrophy) and the secretion of two proteins not previously described as estrogen response markers. UE cell secretion, in particular apical secretion, was stimulated by estradiol but not by progesterone, dexamethasone, or testosterone. Progesterone failed to down-regulate the polarized UE cell responses to estradiol. Collectively, these observations suggest that many of the responses which nominally characterize the action of estrogen on the UE cell in vivo are likely to be initiated by agents other than estrogen, e.g. growth factors.


Evaluation of leachate treatment by trickling filter and sequencing batch reactor processes in Ibadan, Nigeria.
Strong and highly polluting leachate is continuously discharged into Omi stream and its tributaries in Ibadan, southwest Nigeria, from a municipal solid waste landfill. Previous studies have targeted physical and chemical treatment methods, which could not be implemented on site as stand-alone treatment systems. This study explored the bench-scale, trickling filter (TF) and sequencing batch reactor (SBR) treatment processes and assessed the quality of effluents produced. Leachate treatment using TF produced effluents with significant reductions (%) in suspended solids (SS) (73.17%), turbidity (71.96%), biochemical oxygen demand (BOD5) (76.69%) and ammonia (NH3) (59.50%), while SBR produced effluents with reductions in SS (62.28%), BOD5 (84.06%) and NH3 (64.83%). The dissolved oxygen of the reactors was 4.7 and 6.1mg/l, respectively, in TF and SBR. Also, NH3 values reduced marginally; however, nitrification took place significantly, but within permissible limits. The effluents produced by biological treatment processes were better in quality though the mean residual concentrations for colour, SS and dissolved solids; BOD5 and iron were above the national regulatory standards for discharge into surface water bodies. SBR gave a better effluent quality and should be combined with other treatment methods in sequence to produce quality effluents.


Cytotoxic chemotherapy following tandem autotransplants in multiple myeloma patients.
High-dose treatment (HDT) with autologous stem cell transplant (ASCT) is superior to conventional chemotherapy in multiple myeloma. However, relapses eventually occur, especially in the presence of unfavourable cytogenetic abnormalities, high beta-2 microglobulin levels prior to transplant and extensive prior treatment. Cytotoxic consolidation chemotherapy, following tandem transplants (TT), was given to 75 myeloma patients with at least one poor prognostic factor. When their outcome was compared with that of 75 matched controls who received dexamethasone +/- interferon post TT, no event-free or overall survival advantage was observed. Other approaches may be required to improve survival in multiple myeloma.


[A new system for the measurement and analysis of motor activity in mice: effect of several central stimulants].
To estimate the spontaneous motor activity in mice, a new system with highly stable sensitivity and good reproducibility was made, and the effects of five central stimulants were investigated. The apparatus consists of a doughnut-shaped cage with detectors for measuring spontaneous motor activity; i.e., the number of movements, vertical activity, total distance, etc., for every five min. Methamphetamine (0.5, 1 and 2 mg/kg, s.c.) produced an increase in the number of movement and markedly increased total distance. Cocaine (20, 50 and 75 mg/kg, s.c.) caused a marked increase in movement and total distance. Mice injected with 50 mg/kg of cocaine showed long-lasting locomotion with few stops throughout the observation period. Caffeine (10, 30 and 100 mg/kg, s.c.) produced a long-lasting and moderate excitation. Morphine (5, 10 and 20 mg/kg, s.c.) caused a marked increase in continuous locomotion dose-dependently. Apomorphine produced a transient increase in rearing and locomotion at a dose of 1 mg/kg, s.c.; and it produced long-lasting rearing and moderate locomotor activity at 3 mg/kg. These results suggest that this apparatus is able to detect characteristic changes in spontaneous motor activity produced by central stimulants and may be useful for analyzing drug-induced motor activity in mice in more detail.


Validity and reliability of the Iranian version of the Pediatric Quality of Life Inventory™ 4.0 (PedsQL™) Generic Core Scales in children.
This study aimed to investigate the reliability and validity of the Iranian version of the Pediatric Quality of Life Inventory™ 4.0 (PedsQL™ 4.0) Generic Core Scales in children. A standard forward and backward translation procedure was used to translate the US English version of the PedsQL™ 4.0 Generic Core Scales for children into the Iranian language (Persian). The Iranian version of the PedsQL™ 4.0 Generic Core Scales was completed by 503 healthy and 22 chronically ill children aged 8-12 years and their parents. The reliability was evaluated using internal consistency. Known-groups discriminant comparisons were made, and exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted. The internal consistency, as measured by Cronbach's alpha coefficients, exceeded the minimum reliability standard of 0.70. All monotrait-multimethod correlations were higher than multitrait-multimethod correlations. The intraclass correlation coefficients (ICC) between the children self-report and parent proxy-reports showed moderate to high agreement. Exploratory factor analysis extracted six factors from the PedsQL™ 4.0 for both self and proxy reports, accounting for 47.9% and 54.8% of total variance, respectively. The results of the confirmatory factor analysis for 6-factor models for both self-report and proxy-report indicated acceptable fit for the proposed models. Regarding health status, as hypothesized from previous studies, healthy children reported significantly higher health-related quality of life than those with chronic illnesses. The findings support the initial reliability and validity of the Iranian version of the PedsQL™ 4.0 as a generic instrument to measure health-related quality of life of children in Iran.


CGRdb2.0: A Python Database Management System for Molecules, Reactions, and Chemical Data.
This work introduces CGRdb2.0─an open-source database management system for molecules, reactions, and chemical data. CGRdb2.0 is a Python package connecting to a PostgreSQL database that enables native searches for molecules and reactions without complicated SQL syntax. The library provides out-of-the-box implementations for similarity and substructure searches for molecules, as well as similarity and substructure searches for reactions in two ways─based on reaction components and based on the Condensed Graph of Reaction approach, the latter significantly accelerating the performance. In benchmarking studies with the RDKit database cartridge, we demonstrate that CGRdb2.0 performs searches faster for smaller data sets, while allowing for interactive access to the retrieved data.


Taxation and its effect upon public and private health insurance and medical demand.
Multiple tax subsidies are available to many buyers and sellers of health insurance. These subsidies have the potential of creating excess demand for health insurance, which in turn can create excess demand for health services. A review of the literature on the effects of the tax subsidies on the price of health care shows that these subsidies, by raising prices in the medical sector, constrain the Medicare and Medicaid programs' ability to provide access to care for their beneficiaries.


Research on intracranial atherosclerosis from the East and west: why are the results different?
Intracranial atherosclerosis (ICAS) is a major cause of stroke worldwide and is more common in Asians than Caucasians. The study results from the East and West are generally similar, but notable differences exist. For example, studies from the East have reported that ICAS is associated with young age, whereas ICAS seems to be associated with old age in the West. Studies from the East have strongly suggested that mild ICAS associated with branch occlusion is one of the main causes of single subcortical infarction, whereas this aspect has not been considered in stroke classification systems developed in the West. While clopidogrel is commonly used in patients with large artery disease in the West, cilostazol has been more extensively studied and commonly used in ICAS patients in the East. A randomized controlled study from the West reported negative results regarding the efficacy of stenting in ICAS patients due largely to a relatively high rate of periprocedural adverse events, whereas research papers from the East have reported a relatively lower rate of complications. Studies to narrow these East-West gaps should be performed, including risk factor studies using homogenous ethnic populations, studies investigating appropriate classification systems, drug trials in different ethnic populations, and rigorous high standard randomized controlled studies on the efficacy of stenting in Eastern populations.


[Concentration- or time-dependent manner of recombinant bone morphogenetic protein 2 in regulating expression of vascular endothelial growth factor].
To study biological rule of recombinant human bone morphogenetic protein 2 (rhBMP-2) in regulating the expression of vascular endothelial growth factor (VEGF) of adipose-derived stem cells (ADSCs) at different induced concentrations and time points at gene level and protein level. ADSCs were separated from adult human adipose tissues and cultured until passage 3. After ADSCs were induced by rhBMP-2 in concentrations of 0, 50, 100, and 200 ng/mL respectively for 24 hours, and by 100 ng/mL rhBMP-2 for 3, 6, 12, 18, 24, 36, and 48 hours (ADSCs were not induced at corresponding time point as controls) respectively, the VEGF mRNA and protein expressions were detected by RT-PCR and ELISA. The VEGF mRNA and protein expressions induced by rhBMP-2 were concentration-dependent; the expressions were highest in a concentration of 100 ng/mL. The VEGF mRNA expression in concentrations of 50, 100, and 200 ng/mL were significantly higher than that in a concentration of 0 ng/mL (P < 0.05); and the expression in concentration of 100 ng/mL was significantly higher than that in concentrations of 50 and 200 ng/mL (P < 0.05). The VEGF protein expression in a concentration of 100 ng/mL was significantly higher than that in the other concentrations (P < 0.05). The VEGF mRNA and protein expressions induced by rhBMP-2 were time-dependent. The VEGF mRNA and protein expressions at 3 and 6 hours after induction were significantly lower than those of non-induced ADSCs (P < 0.05); the expressions were lower at 12 hours after induction, showing no significant difference when compared with those of non-induced ADSCs (P > 0.05); the expressions reached peak at 18 and 24 hours after induction, and were significantly higher than those of non-induced ADSCs (P < 0.05); the expressions decreased in induced and non-induced ADSCs at 36 and 48 hours, showing no significant difference between induced and non-induced ADSCs (P > 0.05). rhBMP-2 adjusts VEGF expression of ADSCs in a concentration- and time-dependent manner. The optimum inductive concentration of rhBMP-2 is 100 ng/mL, induced to 18-24 hours is a key period when rhBMP-2 is used to promote tissue engineering bone vascularization.


Partial covariate adjusted regression.
Covariate adjusted regression (CAR) is a recently proposed adjustment method for regression analysis where both the response and predictors are not directly observed (Şentürk and Müller, 2005). The available data has been distorted by unknown functions of an observable confounding covariate. CAR provides consistent estimators for the coefficients of the regression between the variables of interest, adjusted for the confounder. We develop a broader class of partial covariate adjusted regression (PCAR) models to accommodate both distorted and undistorted (adjusted/unadjusted) predictors. The PCAR model allows for unadjusted predictors, such as age, gender and demographic variables, which are common in the analysis of biomedical and epidemiological data. The available estimation and inference procedures for CAR are shown to be invalid for the proposed PCAR model. We propose new estimators and develop new inference tools for the more general PCAR setting. In particular, we establish the asymptotic normality of the proposed estimators and propose consistent estimators of their asymptotic variances. Finite sample properties of the proposed estimators are investigated using simulation studies and the method is also illustrated with a Pima Indians diabetes data set.


Hepatitis B Core-Related Antigen as Surrogate Biomarker of Intrahepatic Hepatitis B Virus Covalently-Closed-Circular DNA in Patients with Chronic Hepatitis B: A Meta-Analysis.
Hepatitis B virus (HBV) covalently-closed-circular (ccc)DNA is the key molecule responsible for viral persistence within infected hepatocytes. The evaluation of HBV cccDNA is crucial for the management of patients with chronic HBV infection and for the personalization of treatment. However, the need for liver biopsy is the principal obstacle for the assessment of intrahepatic HBV cccDNA. In the last decade, several studies have investigated the performance of hepatitis B core-related antigen (HBcrAg) as a surrogate of HBV cccDNA amount in the liver. In this meta-analysis, we collected 14 studies (1271 patients) investigating the correlation between serum HBcrAg and intrahepatic HBV cccDNA. Serum HBcrAg showed a high correlation with intrahepatic HBV cccDNA (r = 0.641, 95% confidence interval (CI) 0.510-0.743, p < 0.001). In a head-to-head comparison, we observed that the performance of HBcrAg was significantly superior to that of hepatitis B surface antigen (r = 0.665 vs. r = 0.475, respectively, p < 0.001). Subgroup analysis showed that the correlation between HBcrAg and intrahepatic HBV cccDNA was high, both in hepatitis B e antigen-positive and -negative patients (r = 0.678, 95% CI 0.403-0.840, p < 0.001, and r = 0.578, 95% CI 0.344-0.744, p < 0.001, respectively). In conclusion, the measurement of serum HBcrAg qualifies as a reliable non-invasive surrogate for the assessment of an intrahepatic HBV cccDNA reservoir.


Lung concentrations of telithromycin after oral dosing.
Concentrations of telithromycin were measured in plasma, bronchial mucosa (BM), epithelial lining fluid (ELF) and alveolar macrophages (AM) following multiple oral doses. Concentrations were determined using a microbiological assay. There were 20 subjects in the study, allocated to three nominal time periods: 2, 12 and 24 h. Mean concentrations in plasma, BM, ELF and AM for 2, 12 and 24 h were as follows: 2 h, 1.86 mg/L, 3.88 mg/kg, 14.89 mg/L and 69.32 mg/L; 12 h, 0.23 mg/L, 1.41 mg/kg, 3.27 mg/L and 318.1 mg/L; and 24 h, 0.08 mg/L, 0.78 mg/kg, 0.97 mg/L and 161.57 mg/L. These concentrations of telithromycin in BM and ELF exceeded for 24 h the mean MIC90s of the common respiratory pathogens Streptococcus pneumoniae (0.12 mg/L) and Moraxella catarrhalis (0.03 mg/L), as well as the atypical microorganism Mycoplasma pneumoniae (0.001 mg/L), and suggest that telithromycin may be effective for the treatment of community-acquired pneumonia and chronic obstructive pulmonary disease.


Transition programs in cystic fibrosis centers: perceptions of pediatric and adult program directors.
There is a growing population of adults with cystic fibrosis (CF) and a need for development of adult CF programs. Recommendations for transfer of patients to an adult program include a transition program. Our goal was to assess the current status of transition programs in US CF centers. In addition, we sought to determine the problems related to the transfer of patients to adult programs as perceived by CF center program directors. A survey was sent in 1998 to 110 pediatric and 44 adult program directors at CF centers approved by the Cystic Fibrosis Foundation (CFF), with a response rate of 65.5% and 72.7%, respectively: 22.2% of pediatric centers reported having a non-CFF-approved adult program, and 38.9% had no specific adult program. About one fifth of pediatric centers cited lack of an adult CF physician as an impediment to establishing an adult program. Age (82% of programs; mean, 18.5 years), but not marriage (17.1%) or pregnancy (24.8%), was used as a criterion for transfer. Criteria precluding transfer included patient/family resistance (51.4%), disease severity (50.5%), and developmental delay (46.7%). The concept of transfer is introduced to the patient and family at the time of diagnosis in a minority (14%) of programs. Over one half of the patients did not meet the adult team until the time of transfer. Pediatricians reported higher perceived parent, patient, pediatric staff, and adult staff concerns about transition issues than did adult program directors. We conclude that there is a lack of standardized programs for transfer of CF patients from a pediatric to an adult care setting, and that there are differences between pediatric and adult program directors' perceptions of concerns that CF patients, their families, and the medical teams have about transfer. These differences may impede the successful transition of patients into an adult program.


Arthritis in leprosy.
Leprosy, a chronic granulomatous infection caused by Mycobacterium leprae, classically presents with cutaneous and neurological manifestations. Musculoskeletal involvement though third most common is underdiagnosed and underreported. It may manifest in the form of Charcot's arthropathy, acute symmetrical polyarthritis or swollen hands and feet syndrome during lepra reactions, insidious-onset chronic symmetrical polyarthritis mimicking RA or as isolated tenosynovitis or tenosynovitis associated with arthritis or neuropathy. At times, articular involvement may be the sole presenting manifestation even without cutaneous lesions. Other rheumatological manifestations occasionally reported are enthesitis, sacroiliitis, cryoglobulinaemic vasculitis and DM. With increasing travel of population between tropical and temperate zones, it is likely that rheumatology clinics in countries free of leprosy may come across cases of leprosy with rheumatological manifestations. Delay in diagnosis and management may be detrimental and may result in deformities and loss of function. Not only this, but recent reports of leprosy being diagnosed in native white populations following anti-TNF-α therapy should alert rheumatologists across the globe to be more familiar with this disease. This review is aimed at presenting a comprehensive clinical scenario of various rheumatological manifestations of leprosy to sensitize rheumatologists and physicians across the continents.


Downregulation of SIK2 expression promotes the melanogenic program in mice.
cAMP response element-binding protein (CREB) promotes melanogenesis by inducing microphthalmia-associated transcription factor (Mitf ) gene expression. We report here that the CREB-specific coactivator TORC and its repressor, salt-inducible kinase 2 (SIK2), are fundamental determinants of the melanogenic program in mice. Exposure of B16 melanoma cells to ultraviolet (UV) light results in the immediate nuclear translocation of TORC1, which is inhibited by SIK2. Overexpression of dominant-negative TORC1 also inhibits UV-induced Mitf gene expression and melanogenesis. α-MSH signaling regulates hair pigmentation, and the decrease in α-MSH activity in hair follicle melanocytes switches the melanin synthesis from eumelanin (black) to pheomelanin (yellow). Mice with the lethal yellow allele of agouti (A(y)) have yellow hair because of impaired activation of the α-MSH receptor. To examine the involvement of SIK2 in the regulation of the melanogenesis switch in vivo, we prepared SIK2-knockout mice, and the Sik2(-/-) genotype was introduced into A(y)/a mice. The resultant Sik2(-/-); A(y)/a mice had brown hair, indicating that SIK2 represses eumelanogenesis in mice.


Motor performance is preserved in healthy aged adults following severe whole-body hyperthermia.
Healthy aging is associated with a progressive decline in motor performance and thermoregulatory efficiency. Functional consequences of severe whole-body hyperthermia on neurophysiological functions in healthy aged men have not been investigated. To determine whether severe whole-body hyperthermia (increase in rectal temperature of about 2.5 °C) induced by lower-body heating in older men (64-80 years, n = 9) would suppress excitability of reflexes, voluntarily and electrically induced ankle plantar flexor contractile properties were compared with those in young men (19-21 years, n = 11). Though no aging effect on hyperthermia-induced reflex amplitudes was observed, a decrease in maximal H-reflex and V-wave latencies was found to be greater in older than in young men. In older men, lower-body heating was accompanied by a significant increase in twitch and tetani test torque in parallel with a greater decrease in muscle contraction time. There was no temperature-depended aging effect on the voluntary activation and maximal voluntary torque production. Despite delayed and weakened thermoregulation and age-related decline in neuromuscular function, motor performance in whole-body severe hyperthermia is apparently preserved in healthy aging.


The gender-differentiated antioxidant effects of a lutein-containing supplement in the aqueous humor of patients with senile cataracts.
Antioxidant supplements are expected to decrease oxidative damage and prevent ocular diseases. In this study, changes in the anti-oxidative ability and oxidative status in the aqueous humor before and after intake of a lutein-containing supplement were measured. Forty patients who all had identical grades of cataracts in both eyes were included. The aqueous humor was collected as pre-intake samples during cataract surgery. Ocuvite + Lutein(Ⓡ), an antioxidant supplement, was administered orally beginning the day after surgery. Six weeks later, the aqueous humor was collected as a post-intake sample during cataract surgery of the opposite eye. To determine the anti-oxidative ability, the levels of superoxide (O2(*-)) scavenging activity were measured. To determine the oxidative status, the levels of hydrogen peroxide (H2O2) and total amount of hydroperoxides (TH, including H2O2 and peroxides of lipids, proteins, and nucleic acids) were measured. In post-intake samples, the O2(*-) scavenging activities were significantly higher in both genders (p < 0.05). The levels of H2O2 were significantly higher (p < 0.01) while the levels of TH were significantly lower (p < 0.01) only in females. The level of H2O2 was significantly negatively correlated to the TH in the post-intake samples of both genders (r = -0.50 and p < 0.05 for males; r = -0.59 and p < 0.01 for females) while the level of H2O2 was significantly positively correlated to the O2(*-) scavenging activity in both pre- and post-intake aqueous humor in females only (r = 0.66 and p < 0.01 for pre-intake samples, r = 0.71 and p < 0.01 for post-intake samples). After the introduction of the antioxidant supplement, O2(*-) scavenging activity increased while H2O2 levels remained the same in males, suggesting that scavenging rates are proportional. In postmenopausal females, the superoxide scavenging activity also increased, however unlike in males, the H2O2 levels also increased meaning H2O2 was not completely scavenged. H2O2 is a non-free radical and can be excreted from the aqueous humor to prevent further oxidation of lipids, proteins, and nucleic acids, which was confirmed by the low levels of TH in post-intake samples. Antioxidant supplements are suggested to be effective in reducing oxidation in the aqueous humor by different mechanisms in both genders.


Breastfeeding: What are the Barriers? Why Women Struggle to Achieve Their Goals.
Despite recognized health benefits for both mothers and infants, significant disparities still exist in the rates of breastfeeding in the United States. Major organizations representing the health of women and children (including the Centers for Disease Control and Prevention [CDC], American Academy of Pediatrics [AAP], American Congress of Obstetrics and Gynecology [ACOG], American Academy of Family Physicians [AAFP], United Nations International Children's Emergency Fund (UNICEF), the World Health Organization [WHO], and the United States Public Health Service [PHS]) recommend exclusive breastfeeding, but statistics show that although many women initiate breastfeeding, few meet the recommended goals for duration and exclusivity. This article reviews the evidence related to barriers (prenatal, medical, societal, hospital, and sociocultural) that many mothers face, and explore the known barriers and the impact they have on a woman's ability to breastfeed her infant. Strategies will be discussed to address (and potentially overcome) some of the most common barriers women face along with a list of resources that can be useful in this effort. Gaps in care and areas that need further research will be noted. This article is targeted toward physicians and other healthcare providers who work with women and who can assist with and advocate for the removal of barriers and thereby improve the health of women and children by increasing the rates of breastfeeding initiation, duration, and exclusivity in the United States.


Effects of hypothermia on brain injury induced by status epilepticus.
We investigated the neuroprotective efficacy of hypothermia after status epilepticus (SE) in immature rats. In addition, the expression levels of NMDAR1 and c-Jun were measured to establish a possible signaling mechanism for hypothermia-induced neuroprotection. Pilocarpine-treated rats were randomly divided into 2 groups: group D (diazepam) and group DH (diazepam plus hypothermia). Compared to the control (group NS) rats, Pilocarpine-induced SE significantly enhanced the expression of NMDAR1 and c-Jun in the hippocampus, and also significantly increased the numbers of necrotic and apoptotic pyramidal neurons. The DH group exhibited significantly fewer necrotic and apoptotic hippocampal pyramidal neurons and reduced NMDAR1 expression than group D. In contrast, early expression of c-Jun was significantly higher in the hippocampi of hypothermia-treated rats than in the hippocampi of group D, while late c-Jun expression was significantly lesser than group D. Our results show mild post-ictal hypothermia partially rescues neuronal cell death in the hippocampus following SE. We further suggest that elevated NMDAR1 expression exacerbates SE-induced neuronal death in pilocarpine-treated rats, while early c-Jun overexpression, concomitant with hypothermia, suppresses subsequent neuronal death.


Distinguishing Untreated Osteoblastic Metastases From Enostoses Using CT Attenuation Measurements.
The purpose of this study was to determine whether CT attenuation thresholds can be used to distinguish untreated osteoblastic metastases from enostoses. The study group comprised 62 patients with 279 sclerotic bone lesions found at CT (126 enostoses in 37 patients and 153 metastases in 25 patients). The cause of sclerotic lesions was assessed histologically or by clinical and imaging follow-up. None of the patients had undergone prior treatment for the metastases. The mean and maximum attenuation were measured in Hounsfield units. ROC analysis was performed to determine sensitivity, specificity, AUC, 95% CIs, and cutoff values of CT attenuation to differentiate metastases from enostoses. Interreader reproducibility was assessed using an intraclass correlation coefficient with 95% CI. The mean and maximum CT attenuation values of enostoses were 1190 ± 239 HU and 1323 ± 234 HU, respectively, and those of osteoblastic metastases were 654 ± 176 HU and 787 ± 194 HU, respectively. Using a cutoff of 885 HU for mean attenuation, the AUC was 0.982, sensitivity was 95%, and specificity was 96%. Using a cutoff of 1060 HU for maximum CT attenuation, the AUC was 0.976, sensitivity was 95%, and specificity was 96%. The mean attenuation intraclass correlation coefficient was 0.987 for enostoses and 0.81 for metastases. The maximum attenuation intraclass correlation coefficient was 0.814 for enostoses and 0.980 for metastases. CT attenuation measurements can be used to distinguish untreated osteoblastic metastases from enostoses. A mean attenuation of 885 HU and a maximum attenuation of 1060 HU provide reliable thresholds below which a metastatic lesion is the favored diagnosis.


Anthropometry, lifestyles and fat patterning in Balinese women.
In many parts of the developing world, modernization has resulted in an increase in the prevalence of overweight and obesity and a subsequent rise in nutrition-related, non-communicable diseases such as cardiovascular disease and Type 2 diabetes. The study examined the impact of socio-economic and lifestyle changes associated with modernization on the body size and shape of Balinese women. Anthropometric data including weight, height, body mass index (BMI) and seven skinfolds were collected from 564 Balinese women, aged between 15 and 45 years. The relationship between the degree of 'modernization' (using such parameters as household wealth and education level) and body size and shape was analysed using multiple regression analysis, as was the effect of age, family size and breast-feeding. Using the WHO (WHO 1995) categories of BMI, 14% of Balinese women displayed Chronic Energy Deficiency (BMI < 18.5 kg m(-2)), 7% were overweight (BMI = 25.0-29.9 kg m(-2)) and less than 1% were obese (BMI > or = 30.0 kg m(-2)). Household wealth (p < 0.0001) and education level (p < 0.05) were significantly associated with fatness, while breast-feeding (p < 0.05) was significantly associated with leanness. Fat distribution was largely independent of biological and socio-economic variables. The trend toward increasing fatness associated with greater household wealth and higher education has important health implications for Balinese women as they continue their rapid transition from subsistence agriculture towards a more 'western' lifestyle.


On chaos synchronization and secure communication.
Chaos synchronization, in particular isochronal synchronization of two chaotic trajectories to each other, may be used to build a means of secure communication over a public channel. In this paper, we give an overview of coupling schemes of Bernoulli units deduced from chaotic laser systems, different ways to transmit information by chaos synchronization and the advantage of bidirectional over unidirectional coupling with respect to secure communication. We present the protocol for using dynamical private commutative filters for tap-proof transmission of information that maps the task of a passive attacker to the class of non-deterministic polynomial time-complete problems.


Minimizing cationization effects in the analysis of complex mixtures of oligosaccharides.
We outline simple methodology for the rapid and selective analysis of 2-aminoacridone (2-AMAC) derivatised oligosaccharides by matrix-assisted laser desorption/ionization mass spectrometry. This involves the addition of small amounts of lithium chloride to the matrix before evaporation of solvent and crystallization. Signals mainly attributed to proton, sodium and potassium adducts are suppressed to a great extent, and a single signal due to (M + Li)+ is observed. This technique is rapid and is most useful for the direct analysis of complex glycan mixtures, after derivatization with 2-aminoacridone and without separation of the individual components.


Survey of bovine colostrum quality and hygiene on northern Victorian dairy farms.
One of the major challenges for dairy producers is to produce, harvest, and store high-quality colostrum and feed it to their replacement heifer calves. Limited published data are available in Australia regarding the relationship between colostrum management, hygiene, and quality. The objectives of this study were to investigate (1) the colostrum storage and handling practices carried out on farm; (2) the immunoglobulin concentration and bacterial composition of colostrum being fed to replacement dairy heifer calves; (3) the percentage of colostrum being fed to replacement dairy heifer calves that meet industry recommendations; and (4) risk factors for bacterial contamination of colostrum. The study was carried out on 24 dairy farms located near Rochester, Victoria, Australia. Two hundred forty colostrum samples were collected (10 samples per farm). Each farm harvested and stored first-milking colostrum under normal farm conditions. A 10-mL sample of the colostrum was collected in a sterile container immediately before feeding, and a Brix refractometer reading was taken. The samples were then frozen at -4°C and submitted for bacterial concentration analysis. Fifty-eight percent of colostrum samples met the recommended industry standard of a total plate count (TPC) of <100,000cfu/mL, and 94% of colostrum samples met the recommended industry standard of total coliform count (TCC) of 10,000cfu/mL. However, when all the current industry recommendations for TPC, TCC, and Brix refractometer percentage for colostrum quality were considered, only 23% of the samples met all standards. These findings demonstrate that a large number of calves were at risk of receiving colostrum of poor quality, with high bacterial loads that may have interfered with the acquisition of transfer of passive immunity and affected calf health. Further investigation is required to identify the farm-specific factors that may influence the level of bacterial contamination of colostrum. Recommendations as a result of this study include refrigeration of excess colostrum shortly (within 1h) after collection and thorough disinfection of the calf feeding apparatus before use.


A case of an aortic dissection in a young adult: a refresher of the literature of this "great masquerader".
Aortic dissection is often misdiagnosed, especially among young patients, and it is associated with a high mortality rate. We present here a case of fatal acute aortic dissection in a young man who was misdiagnosed with pericarditis. We reviewed the literature of acute aortic dissection in young people and we focused particularly on clinical presentations, outcomes and investigations of aortic dissection. We report a case of a 33-year-old man with a history of uncontrolled hypertension with acute pleuretic chest pain who was transferred to our hospital for suspected pulmonary embolism and died of acute hemorragic pericardial effusion from an ascendant aortic dissection. We should never rule out aortic dissection off our differential diagnosis on the sole basis of a patient's young age.


Comparative study of convolution, superposition, and fast superposition algorithms in conventional radiotherapy, three-dimensional conformal radiotherapy, and intensity modulated radiotherapy techniques for various sites, done on CMS XIO planning system.
The aim of this study is to compare the dosimetry results that are obtained by using Convolution, Superposition and Fast Superposition algorithms in Conventional Radiotherapy, Three-Dimensional Conformal Radiotherapy (3D-CRT), and Intensity Modulated Radiotherapy (IMRT) for different sites, and to study the suitability of algorithms with respect to site and technique. For each of the Conventional, 3D-CRT, and IMRT techniques, four different sites, namely, Lung, Esophagus, Prostate, and Hypopharynx were analyzed. Treatment plans were created using 6MV Photon beam quality using the CMS XiO (Computerized Medical System, St.Louis, MO) treatment planning system. The maximum percentage of variation recorded between algorithms was 3.7% in case of Ca.Lung, for the IMRT Technique. Statistical analysis was performed by comparing the mean relative difference, Conformity Index, and Homogeneity Index for target structures. The fast superposition algorithm showed excellent results for lung and esophagus cases for all techniques. For the prostate, the superposition algorithm showed better results in all techniques. In the conventional case of the hypopharynx, the convolution algorithm was good. In case of Ca. Lung, Ca Prostate, Ca Esophagus, and Ca Hypopharynx, OARs got more doses with the superposition algorithm; this progressively decreased for fast superposition and convolution algorithms, respectively. According to this study the dosimetric results using different algorithms led to significant variation and therefore care had to be taken while evaluating treatment plans. The choice of a dose calculation algorithm may in certain cases even influence clinical results.


Chemiluminescence measurement of phagocytic activity of pulmonary macrophages in sarcoid alveolitis.
The phagocytic activity of alveolar macrophages in a group of patients with stage I and stage II fresh sarcoidosis has been studied in comparison with a group of healthy volunteers. The phagocytic activity has been measured by means of chemiluminescent emission recording. While no difference in the emission of chemiluminescence has been detected in polymorphonuclear leukocytes of patients and control subjects, a greater emission of chemiluminescence has been noted in the alveolar macrophages of sarcoid patients. Such a difference is statistically significant; its possible relation to alveolar inflammation has been considered.


Predictive factors of a successful testicular biopsy and subsequent clinical pregnancy.
Forecast of success with testicular sperm extraction and intracytoplasmic sperm injection (ICSI) remains unknown, as predictive factors have rarely been studied. We evaluated the association among possible predictive factors and a successful biopsy and clinical pregnancy. A consecutive sample of men submitted to a testicular open biopsy in S. João Hospital was used. Patient's age, medical history, testicular volume, spermogram, genetic testing, endocrinologic results, biopsy results and clinical pregnancy information were collected. From the 113 men included, it was possible to retrieve spermatozoa in 79.6% of the cases, which resulted in 58 fertilisations and 22 clinical pregnancies. Retrieving viable spermatozoa on biopsy was associated with the identification of spermatozoa in the spermogram (100.0% versus 74.4%; P = 0.010), diseases causing obstructive infertility (100.0% versus 79.2%; P = 0.036) and no genetic causes detected (82.4% versus 54.5%; P = 0.030). Successful clinical pregnancy was only associated with lower female partner age (31.7 versus 36.0 year; P = 0.001) but not the quality of the spermatozoa or the time until the reproduction cycle. Identification of spermatozoa in the spermogram, diseases causing obstructive infertility and lack of genetic causes for infertility were associated with higher probability of viable spermatozoa retrieval but the female partner age remained the principal determinant of a successful pregnancy.


Pregnancy termination in the bitch and queen.
Mismate or pregnancy termination is one of the most common "reproductive" requests from dog and cat owners. Ovariohysterectomy is the best alternative for those clients who do not really have a valid reason for keeping a reproductively intact animal. If the animal is a potential breeder, drugs are available that can prevent or terminate pregnancy. The use of these drugs must be based on the safety, efficacy, convenience, compliance in treatment, and cost of the drug. Drugs that can be given during estrus to prevent pregnancy include estrogens and tamoxifen. However, because most dogs presented for mismate are not truly pregnant, a pregnancy examination should be performed before any drug is given to terminate pregnancy. If a dog is known to be pregnant, multiple doses of natural or synthetic prostaglandins can be used throughout pregnancy, whereas multiple doses of prolactin inhibitors (cabergoline, bromocriptine, metergoline) or dexamethasone can be used in the second half of pregnancy. Combined protocols of prostaglandin and prolactin inhibitors are also effective at terminating pregnancy. Progesterone blockers such as mifepristone and aglepristone are effective, but very expensive. Other drugs, such as the isoquinolones and progesterone synthesis inhibitor epostane are available outside of the United States and appear to be very effective at terminating pregnancy. No drug, however, meets all the following criteria of a perfect mismate drug: possible to give at any stage of estrus or pregnancy, 100% effective, causes no vaginal discharge, has no side effects, does not impair future fertility, is readily available, and is inexpensive.


Increased renal Akt/mTOR and MAPK signaling in type I diabetes in the absence of IGF type 1 receptor activation.
Growth hormone (GH) and IGF-I have been implicated in the pathogenesis of type I diabetic (DM) nephropathy. We investigated renal GH receptor (GHR) and IGF-type 1 receptor (IGF1R) signaling in an animal model of type I DM. Kidney tissue was examined for GHR and IGF1R key signaling molecules. GHR levels were unchanged and IGF-I mRNA levels were decreased in the diabetic group (D). Basal and GH stimulated phosphorylated (p-) JAK2 and STAT5 levels were similar in controls (C) and D. The levels of p-IGF1R were similar in the two groups at baseline, while pAkt, pGSK3, p-mTOR, p-rpS6, p-erk1/2 (Mapk), and pSTAT-3 were increased in D. Following IGF-I administration p-Akt, p-rpS6, p-Mapk, and p-GSK levels increased more pronouncedly in D versus C. In conclusion, the lack of JAK2-STAT5 activation and the decrease in kidney IGF-I mRNA levels in D argue against a role for the GH activated JAK2-STAT5 pathway in the pathogenesis of diabetic nephropathy. On the other hand while IGF1R phosphorylation was unchanged, Akt/mTOR and MAPK signaling were hyperactivate in DM, suggesting their involvement. The increase in baseline activated Akt, mTOR, rpS6, and MAPK cannot be explained by activation of the IGF1R, but may be triggered by other growth factors and nutrients.


Surgical management of a giant hepatic cyst with suspicious radiological features.
Cysts in the liver have a wide variety of aetiologies. Important features of malignancy based on various imaging techniques must be considered prior to any intervention. Perioperative decision making in complex or difficult cysts is key to appropriate patient management. A 66-year-old woman was referred to the outpatient department with a one-year history of intermittent, sharp, right upper quadrant pain, radiating to her back. Computed tomography and magnetic resonance imaging showed a large cyst in the right and left lobes of the liver with portal inflow closely related. Features such as wall thickening suspicious for cystadenocarcinoma were present. An open resection was planned but, based on perioperative findings, the cyst had features making it unsafe to perform excision. De-roofing, carefully controlled drainage and assessment of the internal aspect of the cyst were performed, which revealed an extremely close relationship to portal inflow. This case describes the decision-making process when faced with complex indeterminate pathology of the liver and proximity of critical structures.


Inhibition of Full Smooth Muscle Contraction in Isolated Human Detrusor Tissues by Mirabegron Is Limited to Off-Target Inhibition of Neurogenic Contractions.
Mirabegron is used for treatment of storage symptoms in overactive bladder (OAB) caused by spontaneous bladder smooth muscle contractions. However, owing to limitations in available studies using human tissues, central questions are still unresolved, including mechanisms underlying improvements by mirabegron and its anticontractile effects in the detrusor. Here, we assessed concentration-dependent mirabegron effects on contractions of human detrusor tissues in frequency-response curves and concentration-response curves for different cholinergic and noncholinergic agonists. Detrusor tissues were sampled from patients undergoing radical cystectomy. Contractions were induced by electric field stimulation (EFS) and by cumulative concentrations of cholinergic agonists, endothelin-1, and the thromboxane A2 analog U46619. EFS-induced contractions were inhibited using 10 µM mirabegron, but not using 1 µM. Inhibition by 10 µM mirabegron was resistant to the β 3-adrenergic antagonist L-748,337. Concentration-dependent contractions by carbachol were not inhibited by 1 µM or 10 µM mirabegron. Concentration-response curves for methacholine were slightly right-shifted by 10 µM, but not 1 µM mirabegron. Concentration-dependent contractions by endothelin-1 or U46619 were not changed by mirabegron. In contrast, the muscarinic antagonist tolterodine right-shifted concentration-response curves for carbachol and methacholine and inhibited EFS-induced contractions. In conclusion, inhibition of neurogenic contractions in isolated detrusor tissues by mirabegron requires concentrations highly exceeding known plasma levels during standard dosing and the known binding constant (Ki values) for β 3-adrenoceptors. Full contractions by cholinergic agonists, endothelin-1, and U46619 are not affected by therapeutic concentrations of mirabegron. Improvements of storage symptoms are most likely not imparted by inhibition of β 3-adrenoceptors in the bladder wall itself. SIGNIFICANCE STATEMENT: Mirabegron is used for overactive bladder (OAB) treatment, but the underlying mechanisms are unclear, and preclinical and clinical findings are controversial due to limitations in available studies. Our findings suggest that inhibition of detrusor contractions by mirabegron is limited to neurogenic contractions, which requires unphysiologic concentrations and does not involve β 3-adrenoceptors. Mechanisms accounting for improvements of OAB by mirabegron are located outside the urinary bladder.


Dexamethasone inhibition of prostaglandin production in human term placental cells is protein and ribonucleic acid synthesis dependent.
A key enzyme in the regulation of prostaglandin (PG) synthesis is PG synthase (PGS; cyclooxygenase), which converts arachidonic acid to PGs. Since both PGs and glucocorticoids are elevated before parturition, we studied the regulation of dexamethasone (DEX; 150 nM) on PGF2 alpha synthesis and PGS expression in human placental cells in vitro. Both first trimester and term placental cells were used. DEX reduced PGF2 alpha synthesis in human term placental cells, in contrast to first trimester cells which were unaffected by the same treatment. DEX inhibition of PGF2 alpha production by term placental cells was time and dose dependent. PGS expression was analyzed by [35S]methionine metabolic labeling and immunoprecipitation using polyclonal antibodies developed in rabbits against ram seminal vesicle PGS. DEX reduced PGS expression in term placental cells, but not in first trimester cells. In contrast to the effect of DEX on PGF2 alpha, progesterone and estradiol production by cells were unaffected at any stage of gestation examined. DEX inhibition of PGF2 alpha synthesis required de novo biosynthesis of RNA and proteins. These results suggest 1) corticosteroids play a role in the regulation of placental PG synthesis during parturition; 2) the inhibition of PG synthesis and PGS expression by glucocorticoids is RNA and protein biosynthesis dependent; and 3) induction of labor by glucocorticoids is not directly related to changes in placental progesterone or estradiol biosynthesis.


[Nonlinear Kalman filter simultaneous determination of mixture of phenol and 2-chlorophenol].
An analysis method of nonlinear absorbance for binary composition mixture was proposed. The nonlinear absorbance was composed of the contributions from both themselves and the change in their contributions due to mixing, as well as the contribution from their interaction. The mixture of phenol and 2-chlorophenol was simultaneously determined using nonlinear Kalman filter UV spectrophotometry. UV absorption spectra were obtained with 32 standard solutions (range 1-15 mg x L(-1)) and 71 wavelengths(250-290 nm). Standard work matrix of extended Kalman filter was performed from partial least-squares method. The vectors function Jacobi matrix was obtained by linearization of Taylor series for nonlinear absorbance formula. The recovery experiment showed that the extended Kalman filter simultaneous determination of mixture of phenol and 2-chlorophenol that is not only exact, but also stable.


Matrix-free LDI mass spectrometry platform using patterned nanostructured gold thin film.
A novel matrix-free LDI MS platform using a thin film of patterned nanostructured gold, capped with methyl- and carboxy-terminated self-assembled monolayers (SAMs) is presented. Calibration on the matrix-free LDI surface was performed using a peptide standard mixture available for MALDI analysis. MS analysis for limit of detection was performed using angiotensin I peptide. Peptide fragments from standard protein digests of bovine serum albumin, bovine catalase, and bovine lactoperoxidase were used to carry out peptide mass fingerprinting analysis. Sequence coverage of each protein digest and the number of detected peptide fragments were compared with conventional MALDI MS on a standard MALDI plate. Versatility of the nanostructured gold LDI substrate is illustrated by performing MS analysis on a protein digest using different enzymes and by small molecule MS analysis.


Aesthetic surgery economics: lessons from corporate boardrooms to plastic surgery practices.
Healthcare traditionally has been described as not conforming to the laws of economics. Consumers pay for aesthetic surgery directly, thus freeing it from the usual confounding factors and making it more likely to comply with the market forces explained by economics. Recent studies have demonstrated the ability of classic economics to analyze, predict, and optimize the financial environment of aesthetic surgery. This article describes economic principles and how they can be applied to aesthetic surgery. Some of the basic instruments of economics include the study of supply and demand, prices, and price elasticity; capital investments; communication and cooperation; and consumer cognitive limitations. Each of these tools offers plastic surgeons the opportunity to gain improved control of their financial environment.


Vibrotactile frequency discrimination in human hairy skin.
The human capacity for vibrotactile frequency discrimination has been compared directly for glabrous and hairy skin regions by means of a two-alternative, forced-choice psychophysical procedure in five subjects. Sinusoidal vibratory stimuli, delivered by means of a 4-mm-diam probe, were first used to obtain detection threshold values for the two skin sites, the finger tip and the dorsal forearm, at four standard frequencies, 20, 50, 100, and 200 Hz. Values confirmed previous results showing detection thresholds were markedly higher on hairy skin than on glabrous skin. For the discrimination task, each standard frequency, at an amplitude four times detection threshold, was paired with a series of comparison frequencies, and discrimination capacity then was quantified by deriving from psychometric function curves, measures of the discriminable frequency increment (Deltaf) and the Weber Fraction (Deltaf/f), which, when plotted as a function of the four standard frequencies, revealed similar capacities for frequency discrimination at the two skin sites at the standard frequencies of 20, 100, and 200 Hz but an equivocal difference at 50 Hz. Cutaneous local anesthesia produced a marked impairment in vibrotactile detection and discrimination at the low standard frequencies of 20 and 50 Hz but little effect at higher frequencies. In summary, the results reveal, first, a striking similarity in vibrotactile discriminative performance in hairy and glabrous skin despite marked differences in detection thresholds for the two sites, and, second, the results confirm that vibrotactile detection and discrimination in hairy skin depend on superficial receptors at low frequencies but depend on deep, probably Pacinian corpuscle, receptors for high frequencies.


IgG and complement receptors on purified mouse eosinophils and neutrophils.
Mouse eosinophil and neutrophil receptors for IgG and complement have been examined by means of rosette formation, phagocytosis and 51Cr release assays, using mouse monoclonal antibodies and complement-coated sheep erythrocytes. Mouse eosinophils and neutrophils form a high number of rosettes in the presence of mouse complement but eosinophils show a higher requirement for complement molecules. Both types of granulocyte phagocytose complement-coated sheep erythrocytes very actively, although low levels of 51Cr release are obtained. Eosinophils and neutrophils show higher activity in the presence of IgG2b than in the presence of IgG1, and while both cell types are similarly active when the former antibody is used, neutrophils are the more active when IgG1 is used. However, it remains uncertain whether this is a result of the higher binding obtained with the IgG2b monoclonal antibody. Both cell types behave similarly at high antibody concentrations but neutrophils are the more active at high antibody dilutions. The 51Cr release assay is shown to be superior to the rosette assay at it allows comparisons between eosinophils and neutrophils at high antibody concentrations. A time course study indicates that highest values of phagocytosis of opsonized red cells are obtained after 5 minutes rather than the half to one hour incubation periods normally used.


Evaluation of task performance during mentally imaging three-dimensional shapes from plane figures.
Mental imagery is an important theme in psychology. Although the mental rotation task is well known, the complicated functions in mental images with higher spatial perception remain unknown. The aim of this study was to evaluate the task performances during the mental imaging of two- or three-dimensional shapes (14 healthy male students, M age = 24.2 yr., SD = 3.4). The mental-image task to frame a 3D object from actual 2D figures (2D-3D task) had the longest reaction time (p < .01); performance accuracy on this task was lower than for other tasks. The reaction time for the 2D-3D task differed statistically significantly from that on the typical working memory task using the mental image of three 2D figures. Compared with the 2D-3D task, illustration of a simple 3D object would be effective when a quick judgment of high accuracy is required. The feasibility study using an electroencephalogram suggests that the theta-band activity at the middle frontal lobe reflecting the acts of the working memory is related with mental images.


Genotyping of Toxoplasma gondii and Sarcocystis spp. in road-killed wild mammals from the Central Western Region of the State of São Paulo, Brazil.
Road-killed wild animals host zoonotic pathogens such as Toxoplasma gondii, offering a new opportunity for the epidemiological study of these infectious organisms. This investigation aimed to determine the presence of T. gondii and other apicomplexan parasites in tissue samples of 64 road-killed wild animals, using polymerase chain reaction (PCR). Positive samples were then typed by PCR-restriction fragment length polymorphism (RFLP) using 7 markers: SAG1, 5'-3'SAG2, SAG3, BTUB, c29-6, PK1, and Apico. PCR-RFLP targeting 18S ribosomal RNA (rRNA) genes was also performed on all samples to detect other apicomplexan parasites. T. gondii DNA was detected in 16 tissue samples from 8 individual animals, as follows: 1 Cerdocyon thous (crab-eating fox), 1 Didelphis albiventris (white-eared opossum), 1 Lutreolina crassicaudata (lutrine opossum), 2 Myrmecophaga tridactyla (giant anteater), 1 Procyon cancrivorus (crab-eating raccoon), and 2 Sphiggurus spinosus (Paraguay hairy dwarf porcupine). Seven different T. gondii genotypes were identified, 6 of which were novel. Typing by 18S rRNA verified these 16 T. gondii-infected samples, and identified 1 Sarcocystis spp.-infected animal [Dasypus novemcinctus (nine-banded armadillo)]. The amplified T. gondii (GenBank accession No. L37415.1) and Sarcocystis spp. 18S rRNA products were confirmed by sequencing. Our results indicate that T. gondii is commonly present in wild mammals, which act as sources of infection for humans and animals, including other wild species. The approach employed herein proved useful for detecting T. gondii and Sarcocystis spp. in the environment and identifying their natural reservoirs, contributing to our understanding of host-parasite interactions.


Dietary Patterns and Their Association With Symptoms Activity in Inflammatory Bowel Diseases.
Existing studies on diet and inflammatory bowel disease (IBD) have largely focused on evaluating the effects of single nutrients or whole predesigned diets but not on evaluating the effects of diverse dietary patterns. This study applied unsupervised methods to identify dietary patterns of individuals with IBD and evaluated their association with symptoms activity. This retrospective study of adults with IBD collected current clinical data and typical diet recalled from the time when in clinical remission. Discrete dietary structures were defined by k-means clustering. Multivariable logistic regression evaluated the relationship between diet clusters and the presence of active symptoms, while adjusting for age, sex, disease duration, disease behavior, and medication use. Of 691 participants, 36% had Crohn's disease (CD) and 64% had ulcerative colitis (UC) or IBD-unclassified. Five major dietary clusters were identified: 2 resembled a Western diet (WD) (WD1, WD2), 1 resembled a balanced diet, and 2 resembled a plant-based diet (PB) (PB1, PB2). Compared with WD1, PB2 was associated with lower odds of active symptoms for CD (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.12-0.83) and UC (OR, 0.31; 95% CI, 0.15-0.62). PB1 was associated with lower odds of active symptoms for participants with UC (OR, 0.45; 95% CI, 0.23-0.90) but not for participants with CD (OR, 0.95; 95% CI, 0.36-2.51). Diets with increased intake of fruits and vegetables, reduction of processed meats and refined carbohydrates, and preference of water for hydration were associated with lower risk of active symptoms with IBD, although increased intake of fruits and vegetables alone did not reduce risk of symptoms with CD.


[Effects of acupuncture at Neiguan (PC 6) on human brain functional imaging in different functional states].
To study on effects of acupuncture at a same point at physiological or pathological state on brain functional imaging. Electroacupuncture was given at Neiguan (PC 6) of the healthy senile persons (normal group) and the patients of Alzheimer's disease (AD group), and they were scanned on a 1.5 T MRI scanner and the data of functional magnetic resonance imaging (fMRI) were analyzed by Statistical Parametric Mapping (SPM99). The functional imaging of different brain regions were obtained from both the healthy group and the AD group. Both the frontal lobe and the temporal lobe were activated in varying degrees by electroacupuncture at Neiguan (PC 6) in the healthy group. However, the frontal lobe, the temporal lobe and the cingulate gyrus as well as the cerebellum were activated in varying degrees and other brain regions were not activated by electroacupuncture at Neiguan (PC 6) in the AD group. Acupuncture at Neiguan (PC 6) can activate functions of different brain regions in the healthy group and the AD group, indicating that acupuncture at Neiguan (PC 6) has different effects on functional magnetic resonance imaging in different functional states.


Oxygen-derived free radicals induced cellular injury in superior mesenteric artery occlusion shock: protective effect of superoxide dismutase.
This study was designed to investigate the beneficial effect of administration of exogenous superoxide dismutase (SOD) on the inhibition of lipid peroxidation and cellular protection during superior mesenteric artery occlusion shock in rats. Wistar rats were anesthetized with sodium pentobarbital (30 mg/kg body weight), and the superior mesenteric artery occlusion shock model was induced by clamping the superior mesenteric artery for a 60-min period and then releasing the arterial clamp. The following parameters were determined: 1) average arterial blood pressure; 2) survival rate and mean survival time (MST); 3) activities of plasma lysosomal enzymes beta-glucuronidase (beta-G) and acid phosphatase (ACP); and 4) the contents of malondialdehyde (MDA) in visceral tissues. The SOD group received 15,000 U/kg body weight SOD intra-arterially 15 min before release of the clamp. The saline group received intra-arterially a corresponding volume of saline given to the SOD group. The superior mesenteric artery of rats in the control group was not clamped. In the saline group, the contents of MDA presented significant increases (P less than 0.05) in bowel and heart tissues at 1 hr after release of the clamp and showed more significant increases (P less than 0.01-0.05) in bowel, heart, liver, and lung tissues at 2 hr after release of the clamp, when compared with control values. However, the contents of MDA in bowel and heart tissues in the SOD group showed significant decreases (P less than 0.05) compared with values in the saline group and had insignificant changes (P greater than 0.05) compared with control values at 1 hr after release of the clamp. The contents of MDA in bowel, heart, and lung tissues in the SOD group were still lower than those in the saline group (P less than 0.05) at 2 hr after release of the clamp, although they were higher than those in the control group (P less than 0.05). The activities of plasma lysosomal enzymes in the SOD group were much lower than those in the saline group at 1 and 2 hr after release of the clamp. The mean survival time of shocked animals was prolonged when treated with SOD. These results suggested that administration of exogenous SOD may protect cells against lipid peroxidation injury mediated by oxygen-derived free radicals, depress the release of lysosomal enzymes, and prolong the mean survival time of shocked animals.


Multi-band multi-shot diffusion MRI reconstruction with joint usage of structured low-rank constraints and explicit phase mapping.
To develop a joint reconstruction method for multi-band multi-shot diffusion MRI. Multi-band multi-shot EPI acquisition is an effective approach for high-resolution diffusion MRI, but requires specific algorithms to correct the inter-shot phase variations. The phase correction can be done by first estimating the explicit phase map and then feeding it into the k-space signal formulation model. Alternatively, the phase information can be used indirectly as structured low-rank constraints in k-space. The 2 methods differ in reconstruction accuracy and efficiency. We aim to combine the 2 different approaches for improved image quality and reconstruction efficiency simultaneously, termed "joint usage of structured low-rank constraints and explicit phase mapping" (JULEP). The proposed JULEP reconstruction is tested on both single-band and multi-band, multi-shot diffusion data, with different resolutions and b values. The results of JULEP are compared with conventional methods with explicit phase mapping (i.e., multiplexed sensitivity-encoding [MUSE]) and structured low-rank constraints (i.e., MUSSELS), and another joint reconstruction method (i.e., network estimated artifacts for tempered reconstruction [NEATR]). JULEP improves the quality of the navigator and subsequently facilitates the reconstruction of final diffusion images. Compared with all 3 other methods (MUSE, MUSSELS, and NEATR), JULEP mitigates residual structural bias and improves temporal SNRs in the final diffusion image, particularly at high multi-band factors. Compared with MUSSELS, JULEP also improves computational efficiency. The proposed JULEP method significantly improves the image quality and reconstruction efficiency of multi-band multi-shot diffusion MRI, which can promote a broader application of high-resolution diffusion MRI.


Sex Moderated Mediation of the Musculoskeletal Fitness in Relationship between High-Intensive Interval Training Performing during Physical Education Classes and Cardiorespiratory Fitness in Healthy Boys and Girls.
High-intensive interval training (HIIT) is indicated as a means of improving cardiorespiratory fitness (CRF) and musculoskeletal fitness (MSF). The relationship between CRF and MSF was examined too. Little is known about gaining CRF from HIIT independence of MSF in adolescents. Therefore, this study is aimed at investigating whether MSF mediated the relationship between HIIT and CRF and whether sex moderate this relation. The study sample included 122 individuals (45 boys, 77 girls) 16.12 ± 0.38 years of secondary school age. Participants were assigned to the HIIT intervention or control groups. The intervention lasted 14 minutes during one physical education lesson per week for ten weeks. Outcome and potential mediator were residual changes calculated from pre- and postintervention results of MSF components: handgrip (HG), sit-ups (ABS), sit-and-reach (FL), vertical jump (VJ), and Harvard step-test representing cardiorespiratory fitness (CRF). MSF index (MSFI) was calculated as a construct, agglomerating all MSF, and tested its usefulness. HIIT significantly impacted CRF in boys and girls (B = 2.32, p = 0.032; B = 2.28, p = 0.005, respectively). The impact of the HIIT program on the ABS and FL was observed only in girls. The moderation effect of sex was confirmed. Significant effect of HIIT on CRF decreased (B direct < B total) and was no significant after including FL (B = 1.46, p = 0.62)-complete mediation, but no ABS (B = 2.97, p = 0.001)-partial mediation. CRF was mediated by changes in ABS (B = 2.28, p < 0.001) and FL (4.18, p < 0.001). MSFI was not mediating; its usefulness was limited. HIIT is an effective tool in the development of CRF in both sexes. MSF played a limited role in the relationship between HIIT and CRF. It suggested different mechanisms in both sexes: girls who performed better to the HIIT had better values of FL and ABS, but not boys. HIIT intervention involved modifications in ABS or FL, which also influenced the increase of CRF.


Urban policy in Russia: a geographic perspective.
The author "describes current features of the Russian urban settlement system, recounts erroneous planning practices of the past, and prescribes changes for the improvement of settlement planning in the future. [Included] are tables, disaggregated to the economic regional level, showing spatial variations in the number of new cities registered over the period 1927-1989. In [a] modification of conventional former Soviet thinking, a case is made in favor of such processes as polarization of space, agglomeration, spontaneous transformation of urban economic profiles, and place-based rather than norm-based planning."


[Recognition and treatment of chronic wound infection].
Recognition and treatment of a chronic wound infection is an extraordinarily complex task that requires team work and purposeful and graduate resolving of the problem. Chronic wound infection is the most risky complication because it may have fatal outcome for the patient. The principles of best clinical practice include thorough examination of the patient with respect to endogenous diseases and risk factors, defining the locality of infection and wound characteristics, along with clinical symptoms of infection. Based on the wound status, diagnostic procedures are initiated and the causative agent and its sensitivity to antibiotics determined. With respect to the seriousness of the clinical picture, a plan of surgical interventions is developed. The main procedure is debridement, followed by supportive treatment methods, the choice depending on the indications and contraindications. The targeted method of treatment is systemic administration of antibiotics along with debridement. It is important to know that on approaching a chronic infected wound, the principles of sepsis and antisepsis should be observed. In clinical practice, there is a discrepancy between the adopted criteria for efficient treatment based on the evidence-based practice and objective and subjective problems that obstruct it. Thus, according to statistical data, 50% of antibiotics are prescribed wrongly or are rendered inefficient for some reason. Only half of the patients are treated correctly. It is high time to reach consensus on this issue and accept the facts relevant for the treatment of chronic infected wound, i.e. evidence-based medicine.