Predicting death in necrotizing soft tissue infections: a clinical score.
Necrotizing soft tissue infections (NSTIs) are associated with a high mortality rate; however, there is no uniform way to categorize the severity of this disease early in its course. The goal of this study was to develop a clinical score based on data available at the time of initial assessment to aid in stratifying patients according to their risk of death. A cohort of all 350 patients admitted with NSTI to two institutions over a nine-year period was examined retrospectively. Using random split sampling, two datasets were created: Prediction (PD) and validation (VD). Multivariable stepwise regression analysis of the PD identified independent predictors of death using data available at the time of admission. Model performance was evaluated for accuracy, discrimination, and calibration. A clinical score to predict death was created, and using the Trauma and Injury Severity Score (TRISS) methodology, the score was validated on the VD (z-statistic). Six admission parameters independently predicted death: Age > 50 years, heart rate > 110 beats/min, temperature <36 degrees C, white blood cell count > 40,000/mcL, serum creatinine concentration > 1.5 mg/dL, and hematocrit > 50%. The accuracy of this model was 86.8%; the area under the receiver-operating characteristic curve was 0.81, and the Hosmer-Lemeshow statistic was 11.8. Additionally, the score had excellent performance in evaluation on the VD (z-score/statistic 0.23 to - 0.83). A clinical score that categorizes patients with NSTI according to the risk of death was created. It uses simple variables, all available at the time of first assessment. It stratifies patients according to disease severity and can guide the use of aggressive or novel therapeutic strategies and selection of patients for clinical trials.


Interrupting the renin-angiotensin system: the role of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists in the treatment of hypertension.
The renin-angiotensin system has two roles in clinical hypertension: its vasoconstrictor properties directly govern blood pressure, and its actions on arterial smooth muscle, connective tissue, and endothelial integrity affect cardiovascular prognosis. Additionally, the direct actions of angiotensin II on the function and structure of the heart and renal vasculature influence clinical events. Angiotensin-converting enzyme (ACE) inhibitors have produced functional and clinical outcome benefits in clinical trials of patients with congestive heart failure, systolic dysfunction after myocardial infarction, and diabetic nephropathy. Similar favorable trends have been noted in observational studies in hypertension. Because such enzymes as chymase can substitute for ACE, the ACE inhibitors may not completely block angiotensin II formation, although they enhance bradykinin accumulation and secondarily stimulate nitric oxide and vasodilatory prostaglandins. Angiotensin II receptor blockers (ARB) selectively block the angiotensin II type 1 (AT1) receptor that not only mediates the known effects of angiotensin II but, according to recent reports, might be responsible for sequestering angiotensin II molecules in renal and cardiac cells. Moreover, by increasing plasma concentrations of angiotensin II, the ARB stimulate the unblocked angiotensin II type 2 (AT2) receptors, which-if they exist in meaningful numbers in human hypertension-mediate additional vasodilatory and antiproliferative effects. The contrasting actions of these two classes of drugs might be clinically relevant. For example, they may have additive antihypertensive efficacy; they have differing effects on renal plasma flow; and in a small pilot study of patients with congestive heart failure, the ARB demonstrated an apparent advantage in survival. Ongoing clinical trials will try to determine whether the effects of ARB can equal or even exceed the beneficial effects of ACE inhibitors on cardiovascular prognosis.


Increased serum nitric oxide concentration after bariatric surgery--a potential mechanism for cardiovascular benefit.
It is believed that endothelial dysfunction associated with obesity contributes to reduced vascular production of nitric oxide (NO). Weight reduction after bariatric surgery is known to decrease the risk of cardiovascular disease. The purpose of this study was to determine whether bariatric surgery leads to improvement of metabolic markers of endothelial function: serum NO and its precursor (arginine) concentrations in obese patients. Serum NO and L-arginine concentrations were measured in 25 morbidly obese patients directly before and 6 months after bariatric surgery. Moreover, selected parameters that may be involved in development of endothelial dysfunction were also studied. Control group consisted of ten healthy individuals with normal body weight. Six months after bariatric surgery, serum NO concentration was approximately 40% higher than before surgery. Surprisingly, serum NO concentration in nonobese controls was essentially similar to obese patients before surgery. In contrast, serum L-arginine concentration was higher in obese patients than in controls and decreased significantly after surgery. The body weight, blood pressure, triacylglycerols, LDL/HDL-cholesterol ratio, insulin, homeostasis model assessment score (HOMA-index), C-reactive protein, and white blood cell count were higher in obese patients as compared with controls and decreased significantly after surgery. Our results indicate that improvement of insulin resistance, lipidemia, and blood pressure as well as reduction of systemic inflammation after bariatric surgery were associated with the increase of serum NO concentration. We propose that the increase in serum NO concentration contribute to diverse beneficial effects of weight loss after bariatric surgery especially in the context of risk of atherosclerosis.


Angiopoietin-2 expression in breast cancer correlates with lymph node invasion and short survival.
Angiogenic factors produced by tumor cells are essential for tumor growth and metastasis. In our study, the expression of Angiopoietin-1 (ANG1) and Angiopoietin-2 (ANG2) mRNA in archival human breast cancer tumor samples and in 6 breast cancer cell lines was investigated. Total RNA from biopsies of 38 breast cancer patients was extracted and ANG1 and ANG2 mRNA expression was measured by means of quantitative real-time RT-PCR (Taqman). Matching data with available clinicopathologic and biochemical data revealed a significant association between ANG2 expression and axillary lymph node invasion. Univariate and multivariate survival analysis, by means of Kaplan-Meier method and Cox's proportional hazards model, showed significant and independent association between ANG2 mRNA level and both disease-free (p < 0.0001) and overall survival (p < 0.0003). An important fact is that, notwithstanding the small number of cases examined, this association was confirmed also in the group of lymph node-negative patients (DFS, p < 0.003; OS, p < 0.020). Immunohistochemical analysis demonstrated that Ang2 is expressed by both tumor cells and endothelial elements. Expression in tumor cells was confirmed by studying a panel of human breast carcinoma cell lines in culture by RT-PCR. In ZR75.1 and T47D cells, expression of ANG2 mRNA was increased up to 10-fold by treatment with estrogen within 24 hr. Although preliminary, these data suggest a possible role of ANG2 as a prognostic factor for primary breast cancer.


Marking width, calibration from tip and tine diameter of periodontal probes.
The present study comprises an investigation of 7 different probe types, representing currently-marketed major designs (WHO-CPITN, Williams, Michigan), as well as available calibration systems (engraved, etched and painted markings). Width of markings, accuracy of calibration from probe tip, and tine diameter at the tip and at specified points along the tine were assessed, using a stereomicroscope at a magnification of x 40. Blind duplicate measurements of these probe tine characteristics were 100% reproducible to within 0.01 mm. There was an overall range in marking width from 0.00-1.13 mm. The best marking, in that it had no appreciable width and the highest accuracy, was the discrete transition between normal and engraved parts of probes with engraved bands. Mean inaccuracies of different probe sets varied from 0.06 to 0.22 mm. Probes from the same batch from the same production line could differ by more than 0.5 mm in calibration. Mean tip diameter ranged from 0.28 to 0.70 mm. It was concluded that probe tine diameter and calibration should be considered in addition to other variables of periodontal probing. Standardisation of tine characteristics and avoidance of the use of different types or batches in a single study should enhance the accuracy and reproducibility of periodontal probe-dependent measurements.


Theories and models for 1/f(beta) noise in human movement science.
Human motor behavior is often characterized by long-range, slowly decaying serial correlations or 1/f(beta) noise. Despite its prevalence, the role of the 1/f(beta) phenomenon in human movement research has been rather modest and unclear. The goal of this paper is to outline a research agenda in which the study of 1/f(beta) noise can contribute to scientific progress. In the first section of this article we discuss two popular perspectives on 1/f(beta) noise: the nomothetic perspective that seeks general explanations, and the mechanistic perspective that seeks domain-specific models. We believe that if 1/f(beta) noise is to have an impact on the field of movement science, researchers should develop and test domain-specific mechanistic models of human motor behavior. In the second section we illustrate our claim by showing how a mechanistic model of 1/f(beta) noise can be successfully integrated with currently established models for rhythmic self-paced, synchronized, and bimanual tapping. This model synthesis results in a unified account of the observed long-range serial correlations across a range of different tasks.


Coexistence of beta-1 and beta-2 adrenergic receptors in the human heart: effects of treatment with receptor antagonists or calcium entry blockers.
The properties of the binding of [125I]iodopindolol ([125I]IPIN) to beta adrenergic receptors on plasma membranes prepared from right atrial tissue removed during cardiac bypass surgery were investigated. Some of the patients from whom the tissue was removed had been treated before surgery with either a beta adrenergic receptor antagonist or a calcium entry blocker or both. The specific binding of [125I]IPIN to beta adrenergic receptors was saturable, stereoselective and rapidly reversible. Studies of the inhibition of the specific binding of [125I]IPIN by drugs selective for beta-1 or beta-2 adrenergic receptors suggested that both beta-1 and beta-2 adrenergic receptors are present in the tissue, with approximately 55% of the receptors having the properties of beta-2 adrenergic receptors. The density of receptors in patients not treated with beta adrenergic receptor antagonists or calcium entry blockers was approximately 80 fmol/mg of protein, whereas the density of beta adrenergic receptors in treated patients was increased by approximately 50%. The relative proportion of beta-1 to beta-2 adrenergic receptors in subjects treated with beta adrenergic receptor antagonists and/or calcium entry blockers was not significantly different from that in untreated subjects. Studies were also carried out with a limited number of samples of human ventricular muscle obtained from untreated subjects at the time of surgery. The density of receptors was lower than that observed in studies with atrial tissue. However, as with atrial tissue, approximately half of the receptors appeared to be beta-2 adrenergic receptors.


Death by acid rain: VAP or EXIT?
Ventilator-associated pneumonia (VAP) is a new (nosocomial) lower respiratory tract infection diagnosed in mechanically ventilated patients 48 or more hours after intubation. There is no gold standard for establishing the diagnosis and its pathogenesis is iatrogenic and multifactorial. Gastro-oesophageal reflux is common in mechanically ventilated children, but its role in VAP remains speculative. VAP is associated with increased mortality and morbidity, prolonged duration of ventilation and hospital stay, and escalated costs of hospitalisation. VAP 'bundles' are championed as the antidote.


Cloning and characterization of a new isoform of mouse interleukin-18.
Interleukin-18 (IL-18) is a novel proinflammatory cytokine with potent interferon (IFN)-lambda inducing activity that plays an important biological role in the enhancement of the activity of natural killer cells and cytotoxic T lymphocytes. In this study, we have identified a novel short form of IL-18 in mouse, named IL-18s. IL-18s might be an alternative splicing variant of IL-18 and its cDNA contains a 57 bp in-frame deletion. Like IL-18, IL-18s is also widely expressed in mouse tissues. It was suggested that IL-18s might have a caspase-1-dependent mechanism for maturation and secretion similar to that of IL-18: when transfected in COS-7 cells, pro-IL-18s (22 kDa) could be detected, and the mature IL-18s (16 kDa) could also be detected when combined with caspase-1. We observed that recombinant mouse IL-18s did not show any IL-18-like function, and IL-18s could enhance the ability of IL-18 to increase IFN-lambda production by approximately 40% in mouse splenocytes. This effect was observed primarily at relative low concentrations of IL-18, suggesting that IL-18s might regulate the activity of IL-18 in the physiological conditions.


Transplantation of cryopreserved osteochondral Dowel allografts for repair of focal articular defects in an ovine model.
The purpose of this study was to test whether successful cryopreservation of osteochondral tissue is possible and whether, with the appropriate surgical procedure, it can be used for the successful repair of focal articular defects within joints. Fresh (nonfrozen) and snap-frozen (plunged in liquid nitrogen and thawed in a water bath at 37 degrees C, repeated three times) autografts were used as positive and negative controls, respectively. Snap-frozen, frozen (fresh tissue placed in a freezer at -80 degrees C), and cryopreserved (immersed in 10% dimethyl sulfoxide for 30 minutes and then frozen at 1 degrees C/min to -80 degrees C) allografts were transplanted into the knees of adult sheep. Outcomes were evaluated 3, 6, and 12 months after transplantation. The morphological, histological, biochemical, and biomechanical behaviors and characteristics of the graft cartilage, the host cartilage adjacent to the grafts, and the opposing tibial cartilage were assessed. Freezing protocols that yielded poor chondrocyte recovery after thawing (frozen and snap-frozen) resulted in poor overall graft outcome. The cryopreservation protocol, however, resulted in intermediate recovery (50%) of chondrocytes and in intermediate overall graft outcome compared with fresh autografts. The membrane integrity of the allograft chondrocytes immediately following cryopreservation was identified as the most reliable predictor of long-term outcome of the graft. Further improvements in cryopreservation technique may lead to an effective method of banking osteochondral tissue for successful transplantation for the repair of focal defects and larger joint reconstructions.


Long term cultured HL-60 cells are intrinsically resistant to Ara-C through high CDA activity.
Cytarabine (araC) is a highly active antimetabolite against hematological malignancy while the agent shows limited activity for some patients despite maintenance or continued therapy with ara-C-containing regiments. In this study, we focused to elucidate the mechanism of intrinsic resistance to araC. The concentration of intracellular ara-CTP and incorporated ara-CTP were monitored in human leukemia cell line-HL-60 for different passages in parental with its variant HL-60R. The expression of mRNA for deoxycytidine kinase (dCK), cytidine deaminas (CDA), human equilibrative nucleoside transporter 1 (hENT1), and cytosolic 50-nucleotidase II (cN-II) were examined by Real-time PCR in HL-60 and HL-60R for different passages. And activities of two metabolizing enzymes for araC, dCK and CDA were further examined. The results showed that the concentration of intracellular ara-CTP was significantly reduced and the ara-U increased in HL-60 cells for 50 passages compared with the 5 passages, and associated with higher CDA activity. All the factors in HL-60R cells did not change by the incubation of ara-C. In conclusion, the long term cultured cells are intrinsically resistant to ara-C through high CDA activity, but not low DCK activity.


Response of Reticulitermes flavipes (Isoptera: Rhinotermitidae) to disturbance in laboratory arenas at different temperatures and soldier proportions.
This study examined the evacuation response of groups of Reticulitermes flavipes (Kollar) workers after disturbance in laboratory arenas across a range of temperatures (16, 21, and 27 degrees C) and soldier proportions (1, 3, and 5%). Groups of workers and soldiers were disturbed in a central chamber and then monitored during a 5-d period to examine the percentage that initially evacuated, percentage of evacuees that returned, time to evacuate, time to return, and rates (percentage per hour) of evacuation and return between different temperatures and between soldier levels. Disturbance response patterns were observed that generally consisted of partial evacuation followed by movement back into disturbed areas. General alarm responses were observed and initiated specific alarm responses that resulted in more termites eventually returning to disturbed areas than originally evacuated. The typical evacuation response was not observed in groups with 5% soldiers. Instead, clustering in disturbed areas replaced evacuation. Regression revealed significant correlations between temperature and evacuation time, return time, evacuation rate, and return rate, indicating that R. flavipes alarm behaviors are influenced by temperature. There was a significant correlation between soldier proportions and the percentage of evacuees returning to disturbed areas. Analysis of variance (ANOVA) revealed significant differences between temperatures in the time to evacuate, evacuation rate, time to return, and return rate. ANOVA also showed significant differences between soldier proportions in the mean percentage of evacuees from and the rate of return to disturbed areas. Our results demonstrate that temperature influences the rate, but not the magnitude, of alarm response, whereas the influence of soldiers may not be as important in the context of general alarm as specific alarm.


Collision epithelial and stromal tumours of the stomach: a case report.
Collision epithelial and stromal tumours of the stomach are uncommon, and only a few cases have been reported in the literature. We describe a new case of a 54-year-old man who presented with bloody emesis. An oesophagogastroduodenoscopy revealed a stomach induration, and preoperative histological diagnosis was signet ring carcinoma. Total gastrectomy was performed and histological examination revealed a gastric collision tumour composed of gastrointestinal stromal tumour intermixed with a primary signet ring carcinoma. The neoplastic cells of the gastrointestinal stromal tumour were diffusely positive for CD117, while the signet ring cells were positive for cytokeratin. There was no transition between the two components.


Effects of sodium on measuring relative blood volume during hemodialysis differ by techniques.
Recording the relative blood volume is a standard feature of modern dialysis devices, enabling feedback guidance of ultrafiltration and dialysate conductivity. Technically, the process is based on optical or ultrasonic methods. On the grounds of clinical evidence suggesting a malfunction of the optical hemoglobin (Hb)-dependent absorbance method in the presence of sodium changes, we compared the system with the ultrasonic method. Six patients underwent hemodialysis with a step sodium profile (140, 150, 130, and 140 mmol/L, hourly switch), with two dialysis devices featuring the optical and the ultrasonic blood volume detector, respectively. The ultrasonic system recorded a decreasing blood volume throughout the treatment. With the optical method, changes in dialysate sodium led to inverse deviations of the blood volume curve. In another treatment without profile administering, a bolus of hypertonic sodium led to the detection of a rapid 8.7% reduction in blood volume with the optical method, which was not observed with the ultrasonic device. Blood volume monitors using the optical absorbance device are influenced by osmotic changes. An increase in osmolality produces a paradox drop in the measured blood volume and vice versa rendering the monitor inappropriate for use in sodium profiling.


Disseminated intravascular coagulation associated with intratumoral hemorrhage of ovarian cancer.
Ovarian carcinoma usually presents in an indolent manner. A patient with ovarian cancer rarely shows acute clinical features which require immediate medical intervention. We present a 36-year-old Japanese woman with an ovarian tumor, who suffered general fatigue and increased abdominal girth on admission. Her hemoglobin, platelet count and fibrinogen were decreased, and fibrin/fibrinogen degradation products were elevated, which determined the diagnosis of disseminated intravascular coagulation (DIC). Since computed tomography scan and magnetic resonance imaging revealed an intratumoral hemorrhage, an emergency laparotomy was performed. The patient was found to have ovarian cancer with a massive intratumoral hemorrhage, and DIC improved immediately after the operation. The clinician should be alert to the possibility that intratumoral bleeding of ovarian cancer might be associated with DIC.


EDM-DEDM and protein crystal structure solution.
Electron-density modification (EDM) procedures are the classical tool for driving model phases closer to those of the target structure. They are often combined with automated model-building programs to provide a correct protein model. The task is not always performed, mostly because of the large initial phase error. A recently proposed procedure combined EDM with DEDM (difference electron-density modification); the method was applied to the refinement of phases obtained by molecular replacement, ab initio or SAD phasing [Caliandro, Carrozzini, Cascarano, Giacovazzo, Mazzone & Siliqi (2009), Acta Cryst. D65, 249-256] and was more effective in improving phases than EDM alone. In this paper, a novel fully automated protocol for protein structure refinement based on the iterative application of automated model-building programs combined with the additional power derived from the EDM-DEDM algorithm is presented. The cyclic procedure was successfully tested on challenging cases for which all other approaches had failed.


Interactions between Coal and Solvent during the Solvent Extraction of Coal in View of Free Radicals.
In this study, variations in the free radical concentration, degree of swelling (Q), and extraction yield of Buertai coal (C%, 80.4%) in 11 solvents with different characteristics were determined to investigate the interaction between the coal and solvent, as well as the bond cleavage during solvent extraction. Derivative thermogravimetry (DTG) results for the residues and raw coal were compared to confirm whether the covalent bond breaks during solvent extraction. The free radical concentration decreases in certain solvents but increases in a few others. The relative free radical concentration, Q, and extraction yield are positively correlated. The charge-transfer capability of the solvent, and in particular its electron-donating capability, plays an essential role in influencing the interaction between the coal and solvent. The increase in the free radical concentration during solvent extraction can be attributed to (1) the formation or decomposition of charge-transfer complexes, (2) dissociation of charge-transfer complexes into radical ions, and (3) breakage of weak covalent bonds. DTG results show the occurrence of weak covalent bonds breakage at temperatures of 133.9-320.1 °C during solvent extraction due to the reduction of the bond energy caused by the formation of radical ions.


A simple salt solution medium supplemented with yolk plasma and lactate (YPLM) supports development of preimplantation bovine embryos in vitro.
This study investigated the embryotropic potential(s) of egg yolk (EY) or its fractions, yolk plasma (YP) and yolk granules (YG), in culturing bovine embryos in vitro and substituting for protein (FCS, BSA, and BME-E and MEM-NE amino acids) and energy (glutamine, pyruvate and L-lactate) supplements commonly added to culture medium. In the first set of experiments (Experiment 1, 2 and 3) CR1aa with buffalo rat liver (BRL) cells were used as a co-culture system. The addition of 2.5% or 5% EY significantly increased (P<0.05) blastocyst percent over the BRL control (48.3% and 52.4% vs. 32.5%, respectively). The addition of 5% EY in the absence of FCS and BSA resulted in percent development to blastocysts and hatched blastocysts similar (P>0.05) to those of the BRL control (37.6% and 57.4% vs. 51.5%, 22.7% and 39.5%, respectively). The supplementation of the BRL control with 5% YP compared to that of EY resulted in comparable (P>0.05) percentages of blastocysts and hatched blastocysts (39.0% and 51.6% vs. 40.0% and 58.3%, respectively). In the second set of experiments, the embryotropic potential of YP was examined using a cell-free culture system and a simple salt solution (SS) of NaCl, KCl and NaHCO3 as the base medium. The supplementation of an energy-supplemented cell-free simple salt solution (E-SS) with 5% YP in the absence of supplemental protein resulted in percent development into blastocysts and hatched blastocysts comparable (P>0.05) to those of a BRL control (39.2% and 15.8% vs. 37.1% and 22.2%, respectively). The addition of YP to the simple salt solution with hemicalcium L-lactate as the only supplemented energy ingredient resulted in percentages of blastocysts and hatched blastocysts similar (P>0.05) to those obtained by the supplementation of all energy sources (27.4% and 15.6% vs. 36.4% and 14.0%, respectively). Increasing hemicalcium L-lactate level from 5 to 10, 20 or 25 mM resulted in a significant decrease (P<0.05) in percent development into blastocysts (36.5% vs. 24.8%, 11.6% and 6.7%, respectively). In conclusion, YP, with the advantage of being clearer than EY, is capable of sustaining embryo development to the blastocyst stage in a simple salt solution of NaCl, KCl and NaHCO3 supplemented with hemicalcium L-lactate.


Characterization of Klebsiella pneumoniae Coproducing KPC and NDM-1 Carbapenemases from Turkey.
Aims: The emergence of multidrug-resistant and carbapenem-resistant Klebsiella pneumoniae has became a major public health threat. In this study, we describe the characteristics of isolates coproducing KPC and NDM-1 carbapenemases from patients hospitalized at an emergency unit in Ankara, Turkey, between January and August 2018. The isolates were characterized by antibiogram susceptibility, carbapenemase and extended-spectrum beta-lactamase production, plasmid-mediated colistin (COL) resistance, and high-level aminoglycoside resistance. Pulsed field gel electrophoresis (PFGE), sequencing, wzi typing, multilocus sequence typing, and plasmid analysis were used to investigate the epidemiological relationship between the isolates. Results: All isolates were found to be resistant to amoxicillin-clavulanic acid, piperacillin-tazobactam, cefotaxime, cefoxitin, cefuroxime, ceftazidime, cefepime, imipenem, meropenem, ertapenem, amikacin, gentamicin, ciprofloxacin, levofloxacin, and trimethoprim-sulfamethoxazole. The minimum inhibitory concentration values for imipenem, meropenem, and ertapenem were >32 μg/mL, and >256 μg/mL for amikacin and gentamicin, and two isolates were found to be susceptible to both tigecycline and COL. All strains were positive for SHV, CTX-M, and rmtC, and negative for mcr-1 genes. A/C and FIIAS plasmids were found in all isolates. All isolates had the same PFGE pattern: wzi type 93 and ST15. Conclusion: Here, we have documented the characteristics of KPC- and NDM-1-coproducing isolates that harbored SHV, CTX-M, and rmtC and were typed as wzi 93 and ST15. We conclude that continuous monitoring of carbapenemases for unusual carbapenemase production is crucial to prevent the spread of these powerful isolates.


Modulation of AMPA receptors by a novel organic nitrate.
Positive modulators of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) channels reduce desensitization and alter their gating kinetics. We have discovered a novel compound nitric oxide-mimetic that similarly modulates the AMPA receptor by reducing desensitization. This, designated GT-005, belongs to the organic nitrate family that includes the nitrovasodilator nitroglycerine. In acutely isolated hippocampal neurons, GT-005 enhanced kainate (100 microM)-evoked currents with an EC50 of 1.7+/-0.2 mM and a 176+/-10% maximal increase in the steady-state current response. Similar results were found in cultured hippocampal neurons (EC50 of 1.3+/-0.2 mM and a maximal 83+/-14% increase in the steady-state current response). GT-005 reduced the desensitization of glutamate-evoked currents and slowed the onset of desensitization. This compound also increased the rate of recovery from the desensitized state. With respect to alteration of the excitatory synaptic transmission, GT-005 delayed the decay and increased the frequency of spontaneous miniature excitatory postsynaptic currents (mepsc) recorded in cultured hippocampal neurons.


Supramolecule-to-supramolecule transformations of coordination-driven self-assembled polygons.
Two types of supramolecular transformations, wherein a self-assembled Pt(II)-pyridyl metal-organic polygon is controllably converted into an alternative polygon, have been achieved through the reaction between cobalt carbonyl and the acetylene moiety of a dipyridyl donor ligand. A [6 + 6] hexagon is transformed into two [3 + 3] hexagons, and a triangle-square mixture is converted into [2 + 2] rhomboids. 1H and 31P NMR spectra are used to track the transformation process and evaluate the yield of new self-assembled polygons. Such transformed species are identified by electrospray ionization (ESI) mass spectrometry. This new kind of supramolecule-to-supramolecule transformations provides a viable means for constructing, and then converting, new self-assembled polygons.


[Study on temperature correction of near-infrared spectra of solution].
The near-infrared spectrum of some common solvents, such as water, has very high sensitivity to temperature. So, the effect of temperature can not be ignored in NIRS. When temperature changes, the transmission spectra of the solution will also change. The influence of the temperature was deduced theoretically based on the Lambert-Beer's law in the present paper. And a method for temperature correction of sample's spectra was proposed. By using the change in pure solvent's absorbency with temperature disturbance, the method is used to correct the spectra of prediction samples. The spectra of glucose aqueous solution and albumin aqueous solution were measured at different temperatures. The calibration models of glucose and albumin concentration prediction were built respectively by using the calibration sample's spectra at 30 degrees C. The absorbency of pure water has different value at different temperature, and this difference was used to correct the spectra of sample which was measured at temperatures other than 30 degrees C. The experiment results showed that the curves of absorbancy difference of prediction samples, which were measured at different temperatures, show good superposition after spectra correction. And the root mean square error (RMSEP) of prediction was reduced obviously. It also means that the influence of temperature on the spectra can be eliminated effectively after spectra correction by using the method proposed in this paper.


Differences in household characteristics by income distribution in Pakistan.
The authors examine household characteristics by income distribution in Pakistan using data from the 1979 Population, Labour Force and Migration (PLM) Survey. Tabular data, organized by measures of income and expenditure, are presented on average household size, dependency ratios, average number of children and average number of adults, proportion of female household members, labor force participation rates for various ages, and occupational status of heads of households. The authors conclude that "the findings for Pakistan generally are in consonance with those for other Third World countries and confirm that certain characteristics are associated with poverty." Comments by Karol J. Krotki are also included (pp. 668-9).


TLR2 stimulation induces cardiac inflammation but not cardiac depression in vivo.
Bacteria such as Staphylococcus aureus induce myocardial dysfunction in vivo. To rectify conflicting evidence about the role of TLR2 signaling and cardiac dysfunction, we hypothesized that the specific TLR2 agonist purified lipoteichoic acid (LTA) from S. aureus contributes to cardiac dysfunction in vitro and in vivo. Wildtype (WT-) and TLR2-deficient (TLR2-D) mice were challenged with LTA and in comparison with equivalent doses of lipopolysaccharide (LPS) and CpG-oligodeoxynucleotide (CpG-ODN). TLR2-expression, NFκB as well as cytokine response were determined. Sarcomere shortening of isolated cardiomyocytes was analyzed in vitro and cardiac function in vivo after stimulation with LTA. LTA induced up-regulation of TLR2 mRNA, activation of NFκB and cytokine expression within 2-6 h in WT-, but not in TLR2-D hearts. Cytokines were also elevated in the serum. LPS and CpG-ODN induced a more severe cardiac inflammation. In vitro incubation of cardiomyocytes with LTA reduced sarcomere shortening via NO at stimulation frequencies ≤ 8 Hz only in WT cells. However, hemodynamic parameters in vivo were not affected by LTA challenge. LTA induced cardiac inflammation was relatively weak and sarcomere shortening was reduced only below physiological heart rates. This may explain the apparent contradiction between the in vivo and in vitro LTA effects.


Exploring neovascular age-related macular degeneration and diabetic macular edema and advances in treatment.
Retinal and choroidal vascular diseases are principal causes of blindness for adults in developed countries around the world. Neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) are 2 significant contributors to this global vision loss and confer substantial social and economic burdens on patients and society. Anti-vascular endothelial growth factor intravitreal injection therapy has dominated as the standard of care treatment for over 15 years, but poor adherence and high treatment burden have led to suboptimal visual outcomes in the real world compared with the clinical trial results. New treatments are emerging that expand the therapeutic targets and use innovative delivery mechanisms with longer durability to ease the treatment burden. Understanding the benefits and drawbacks of these therapies is key to designing new treatment pathways that improve visual outcomes while decreasing the treatment burden on patients and healthcare institutions.


Expanding the concept of parental control: a role for overt and covert control in children's snacking behaviour?
The existing literature on parental control and children's diets is confusing. The present paper reports two studies to explore an expanded conceptualisation of parental control with a focus on overt control which 'can be detected by the child' and covert control which 'cannot be detected by the child'. In study 1, 297 parents of children aged between 4 and 11 completed a measure of overt control and covert control alongside ratings of their child's snacking behaviour as a means to assess who uses either overt or covert control and how these aspects of parental control relate to a child's snacking behaviour. The results showed that lighter parents and those with children perceived as heavier were more likely to use covert control and those from a higher social class were more likely to use overt control. Further, whilst greater covert control predicted a decreased intake of unhealthy snacks, greater overt control predicted an increased intake of healthy snacks. In study 2, 61 parents completed the same measure of overt and covert control alongside the three control subscales of the Child Feeding Questionnaire [Birch, L.L., Fisher, J.O., Grimm-Thomas, Markey, C.N., Sawyer, R. (2001). Confirmatory factor analysis of the Child Feeding Questionnaire: A measure of parental attitudes, beliefs and practices about child feeding and obesity proneness. Appetite, 36, 201-210] to assess degrees of overlap between these measures. The results showed that although these five measures of control were all positively correlated, the correlations between the new and existing measures indicated a maximum of 21% shared variance suggesting that covert and overt control are conceptually and statistically separate from existing measures of control. To conclude, overt and covert control may be a useful expansion of existing ways to measure and conceptualise parental control. Further, these constructs may differentially relate to snacking behaviour which may help to explain some of the confusion in the literature.


Antimicrobial α-defensins as multi-target inhibitors against amyloid formation and microbial infection.
Amyloid aggregation and microbial infection are considered as pathological risk factors for developing amyloid diseases, including Alzheimer's disease (AD), type II diabetes (T2D), Parkinson's disease (PD), and medullary thyroid carcinoma (MTC). Due to the multifactorial nature of amyloid diseases, single-target drugs and treatments have mostly failed to inhibit amyloid aggregation and microbial infection simultaneously, thus leading to marginal benefits for amyloid inhibition and medical treatments. Herein, we proposed and demonstrated a new "anti-amyloid and antimicrobial hypothesis" to discover two host-defense antimicrobial peptides of α-defensins containing β-rich structures (human neutrophil peptide of HNP-1 and rabbit neutrophil peptide of NP-3A), which have demonstrated multi-target, sequence-independent functions to (i) prevent the aggregation and misfolding of different amyloid proteins of amyloid-β (Aβ, associated with AD), human islet amyloid polypeptide (hIAPP, associated with T2D), and human calcitonin (hCT, associated with MTC) at sub-stoichiometric concentrations, (ii) reduce amyloid-induced cell toxicity, and (iii) retain their original antimicrobial activity upon the formation of complexes with amyloid peptides. Further structural analysis showed that the sequence-independent amyloid inhibition function of α-defensins mainly stems from their cross-interactions with amyloid proteins via β-structure interactions. The discovery of antimicrobial peptides containing β-structures to inhibit both microbial infection and amyloid aggregation greatly expands the new therapeutic potential of antimicrobial peptides as multi-target amyloid inhibitors for better understanding pathological causes and treatments of amyloid diseases.


Prevention of post-operative venous thromboembolism by a new low molecular weight heparin fraction.
The efficacy of low molecular weight heparin (LMW heparin) was assessed in 550 patients over the age of 40 years, undergoing a variety of elective major surgical procedures. LMW heparin fraction (CY 216, Choay Laboratories, Paris) was used in this study. Each patient received a single injection of 1,850 APTT units of LMW heparin 2 h before surgery, and the same dose was repeated daily for at least 7 days post-operation. Fibrinogen uptake test and ventilation perfusion lung scanning were used to confirm the presence of thromboemboli. Of 501 patients in whom the protocol had been accurately followed, 17 (3.4%) developed DVT, in none were thrombi bilateral. 22 (4.4%) died during the post-operative period. In none of the autopsied patients could emboli be demonstrated. Blood loss during surgery was considered to be excessive in 32 (6.4%). In 19 (3.8%), subcutaneous haematoma developed at the site of abdominal incision. The data presented in this paper indicates that a single daily injection of 1,850 APTT units of LMW heparin is a convenient and safe methods of preventing post-operative venous thromboembolic complications in patients undergoing major abdominal surgery.


Photomanipulation of Minimal Synthetic Cells: Area Increase, Softening, and Interleaflet Coupling of Membrane Models Doped with Azobenzene-Lipid Photoswitches.
Light can effectively interrogate biological systems in a reversible and physiologically compatible manner with high spatiotemporal precision. Understanding the biophysics of photo-induced processes in bio-systems is crucial for achieving relevant clinical applications. Employing membranes doped with the photolipid azobenzene-phosphatidylcholine (azo-PC), a holistic picture of light-triggered changes in membrane kinetics, morphology, and material properties obtained from correlative studies on cell-sized vesicles, Langmuir monolayers, supported lipid bilayers, and molecular dynamics simulations is provided. Light-induced membrane area increases as high as ≈25% and a ten-fold decrease in the membrane bending rigidity is observed upon trans-to-cis azo-PC isomerization associated with membrane leaflet coupling and molecular curvature changes. Vesicle electrodeformation measurements and atomic force microscopy reveal that trans azo-PC bilayers are thicker than palmitoyl-oleoyl phosphatidylcholine (POPC) bilayers but have higher specific membrane capacitance and dielectric constant suggesting an increased ability to store electric charges across the membrane. Lastly, incubating POPC vesicles with azo-PC solutions results in the insertion of azo-PC in the membrane enabling them to become photoresponsive. All these results demonstrate that light can be used to finely manipulate the shape, mechanical and electric properties of photolipid-doped minimal cell models, and liposomal drug carriers, thus, presenting a promising therapeutic alternative for the repair of cellular disorders.


High Re-Operation Rates Using Conserve Metal-On-Metal Total Hip Articulations.
Metal-on-metal hip articulations have been intensely debated after reports of adverse reactions and high failure rates. The aim of this study was to retrospectively evaluate the implant of a metal-on.metal total hip articulation (MOM THA) from a single manufacture in a two-center study. 108 CONSERVE(®) MOM THA were implanted in 92 patients between November 2005 and December 2010. Patients had at time of retrospective evaluation their journals reviewed for re-operations and adverse reactions. 20 hips were re-operated (18.4%) at a mean follow up of 53 months. 4 pseudotumors were diagnosed at time of follow up but no substantiated link was made between adverse reactions and re-operations. The high re-operation rates found in this study raised concern about the usage of the MOM THA and subsequently lead to the termination of implantation of this MOM THA at the two orthopaedic departments.


The Impediments of Cancer Stem Cells and An Exploration into the Nanomedical Solutions for Glioblastoma.
Glioblastoma is an aggressive and recurrent tumour that affects our brain and spinal cord with an extensively poor prognosis and death of the patient within 14-15 months of diagnosis. The tumour originates from astrocytes and therefore comes under the glioma known as astrocytoma. These tumours exhibit miscellaneous properties and contain cancer stem cells (CSCs). The stem cells exhibit diverse mechanisms through which these cells indulge in the proliferation and renewal of their systems. CSCs pose a significant obstacle as far as a cancer therapy is concerned, which incorporates blocking important signalling pathways involved in CSCs' self-renewal and survival which may also include inhibition of the ATP-binding cassette transporters. Nanomedicine, biomarkers and drug delivery technologybased approaches using nanoparticles have tremendous ability to tackle the restrictions impending clinical applications, such as diagnosis and targeting of CSC-specific agents. Nanocarrier-based therapeutic agents have shown the potential of penetrating CSCs and increasing drug accumulation in CSCs. Nanomedicine can overcome ATP-driven pumpmediated multidrug resistance while also reducing the harmful effects on non-cancerous cells. The objective of this review is to examine the advantages of nanomedicine and the innovative approaches that have been explored to address the challenges presented by CSCs in order to control the progression of glioblastomas by developing novel nanotherapeutic interventions which target CSCs.


At the Bench: Pre-clinical evidence for multiple functions of CXCR4 in cancer.
Signaling through chemokine receptor, C-X-C chemokine receptor type 4 (CXCR4) regulates essential processes in normal physiology, including embryogenesis, tissue repair, angiogenesis, and trafficking of immune cells. Tumors co-opt many of these fundamental processes to directly stimulate proliferation, invasion, and metastasis of cancer cells. CXCR4 signaling contributes to critical functions of stromal cells in cancer, including angiogenesis and multiple cell types in the tumor immune environment. Studies in animal models of several different types of cancers consistently demonstrate essential functions of CXCR4 in tumor initiation, local invasion, and metastasis to lymph nodes and distant organs. Data from animal models support clinical observations showing that integrated effects of CXCR4 on cancer and stromal cells correlate with metastasis and overall poor prognosis in >20 different human malignancies. Small molecules, Abs, and peptidic agents have shown anticancer efficacy in animal models, sparking ongoing efforts at clinical translation for cancer therapy. Investigators also are developing companion CXCR4-targeted imaging agents with potential to stratify patients for CXCR4-targeted therapy and monitor treatment efficacy. Here, pre-clinical studies demonstrating functions of CXCR4 in cancer are reviewed.


[Clinical significance of the determination of blood lactate in perinatology].
The paper substantiated the clinical diagnostic significance of lactate tests in various abnormalities. It presents the results of the past 25 years' research and practical studies of blood lactic acid in pregnant women and neonatal infants. More than 1000 pregnant women and 200 neonates were examined. The established peripheral blood lactate standards for pregnant women and the newborn and the values of lactic acid in varying hypoxia are given. It is concluded that lactate tests are of diagnostic value in perinatology.


Patient engagement and shared decision-making: What do they look like in neurology practice?
Neurology is inherently patient-centered given that clinical uncertainty is common, forcing physicians, patients, and families to partner on treatment approach. An increasing emphasis on patient-centered care, patient engagement, and shared decision-making (SDM) in health care provides neurologists with an opportunity to reassess current clinical approaches to decision-making. Such assessment is not simply theoretical but has clear practice implications, with patients indicating a desire for SDM and calls for reimbursement to be tied to demonstration of SDM in practice. We present a framework for how neurologists enhance patient-centered practice by (1) eliciting patients' values and goals, (2) targeting discussion of clinical options to those values and goals, and (3) partnering with patients to make individualized decisions. We also highlight resources that facilitate SDM and examples of SDM in neurology clinical practice.


Benefits of quiet time for neuro-intensive care patients.
The primary mission of any intensive care unit (ICU) is to provide critically ill patients with high-quality care and an atmosphere in which to recuperate. However, all too often, the intensive environment, which is often busy, chaotic, and noisy, may contribute to just the opposite. Patients overstimulated with noise, lights, and other distractions often suffer from sleep deprivation. Research in medicine and nursing has shown that sleep deprivation can have detrimental effects on an ailing patient. Therefore, a quiet time program was developed in the neuro-ICU to reduce noise and light levels, with the ultimate goal to allow sleep. Quiet time, a period of reduced controllable noise and light, took place twice daily coinciding with circadian rhythms. The study included 50 neuro-ICU patients, 35 observed during day hours and 15 observed during night hours. Noise and light levels were measured at multiple locations before, during, and after quiet time hours. Patients' sleep behavior was recorded every half hour, beginning 1/2 hour before quiet time until 30 minutes after. Analysis of data, adjusted for multiple testing and repeated measures on patients, demonstrated significantly lower noise and light levels during day shift quiet time. In addition, patients were significantly more likely to be observed sleeping during day shift quiet time hours.


PPARα Ameliorates Doxorubicin-Induced Cardiotoxicity by Reducing Mitochondria-Dependent Apoptosis via Regulating MEOX1.
Doxorubicin (DOX), a chemotherapeutic drug widely used in the clinical setting, is known to cause serious cardiotoxicity and greatly reduces the survival rate as well as quality of life of patients receiving chemotherapy. Peroxisome proliferation activated receptor α (PPARα) is a type of ligand activated receptor of the nuclear hormone receptor family that regulates multiple gene expression. Several studies have shown that PPARα has anti-apoptotic and cardio-protective effects. However, its role in DOX-induced cardiotoxicity is rarely reported. In this study, we observed decreased expression of PPARα in the heart of tumor-bearing mice already treated with DOX; however, no such phenomenon was observed in tumor tissues. Next, we observed that the PPARα agonist, fenofibrate (FENO), had no effect on tumor progression; however, it enhanced cardiac function in tumor-bearing mice treated with DOX. Subsequently, recombinant adeno-associated virus serotype 9 (rAAV9) was used to manipulate the expression of PPARα in the heart of DOX-induced mice. Our results showed that PPARα gene delivery reduced cardiac dysfunction and mitochondria-dependent apoptosis in DOX-induced mice. Furthermore, we found that PPARα directly regulated the expression of mesenchyme homeobox 1 (MEOX1). Most importantly, the cardioprotective effects of PPARα could be neutralized by knocking down MEOX1. In summary, PPARα plays a vital role in DOX-induced cardiotoxicity and is a promising treatment target.


[Hypodensities accompanying various meningiomas in x-ray computed tomography].
This is a review of 80 cases of intracranial meningiomas, which were operated on in the neurosurgical Service of Lausanne. 51 tumors were associated with an area of low attenuation of variable extension on the CT-scan. In 49 of these, the low attenuation areas corresponded to oedema. In two of them a cyst was discovered at operation. One was a subarachnoid cyst and the other one was an intracerebral cyst separated from the tumor by a thin layer of cerebral cortex. A correlation was attempted between these areas of low attenuation and the clinical history, the CT-scan characteristics, the location, the macroscopic appearance at operation and the histology of the tumors. From these data, the typical features of a meningioma more likely to be associated with an area of low attenuation on the CT-scan were determined. This tumor is often located in the subfrontal area or in the middle base of the skull, and epilepsy or increased intracranial pressure are more likely to be present. The most common histological type is syncytial.


An abnormality of arachidonic acid metabolism is not a generalized phenomenon in patients with aspirin-induced asthma.
Aspirin (ASA)-induced asthma is a distinct clinical syndrome in which bronchoconstrictive response to nonsteroidal anti-inflammatory drugs can be predicted on the basis of their in vitro activity as inhibitors of cyclooxygenase. In ten ASA-sensitive asthmatics and ten matched healthy controls we measured 12-hydroxy-eicosatetraenoic acid (12-HETE) production by platelets and 5-hydroxy-eicosatetraenoic acid (5-HETE) and leukotriene B4 (LTB4) production by polymorphonuclear leucocytes. The blood cells were obtained before administration of the threshold doses of ASA and during the ASA-induced reactions. Initial levels of eicosanoids determined did not differ between the two groups. In both groups, after ASA challenge, 12-HETE rose to similar levels while 5-HETE and LTB4 remained unchanged. These data do not support the concept that an abnormality in the regulation of arachidonic acid oxidative pathways in ASA-sensitive asthmatics is a generalized phenomenon which embraces the platelets and leucocytes; rather it is inhibition of cyclo-oxygenase within the tissues of the respiratory tract that triggers asthmatic attacks in the sensitive patients.


In vitro-generated MDSCs prevent murine GVHD by inducing type 2 T cells without disabling antitumor cytotoxicity.
Myeloid-derived suppressor cells (MDSCs) inhibit T-cell expansion and functions by versatile mechanisms such as nutrient depletion, nitrosylation, or apoptosis. Since graft-versus-host disease (GVHD) is characterized by the expansion of donor-derived T cells destroying recipient tissue, we analyzed whether MDSCs can be used for GVHD prevention in murine allogeneic bone marrow transplantation models. Transplantation of MDSCs, generated from bone marrow cells by granulocyte-macrophage colony-stimulating factor (GM-CSF)/G-CSF in vitro, inhibited GVHD-induced death and attenuated histologic GVHD, whereas antitumor cytotoxicity of alloantigen-specific T cells was maintained. MDSCs expanded in vivo and invaded lymphatic and GVHD target organs. Major histocompatibility complex class I expression on MDSCs was dispensable for their suppressive capacity. Inhibition of GVHD required the presence of MDSCs during T-cell priming, whereas allogeneic T-cell numbers and homing in lymphoid and GVHD target organs were not considerably affected in MDSC-treated mice. However, MDSCs skewed allogeneic T cells toward type 2 T cells upregulating T helper 2 (Th2)-specific cytokines. Type 2 T-cell induction was indispensable for GVHD prevention since MDSC treatment failed to prevent GVHD when allogeneic STAT6-deficient T cells, which are unable to differentiate into Th2 cells, were transplanted. MDSC-induced Th2 induction might be applicable for GVHD treatment in clinical settings.


Molecular phylogenetics and morphological reappraisal of the Platanthera clade (Orchidaceae: Orchidinae) prompts expansion of the generic limits of Galearis and Platanthera.
The Platanthera clade dominates the North American orchid flora and is well represented in eastern Asia. It has also generated some classic studies of speciation in Platanthera sections Platanthera and Limnorchis. However, it has proved rich in taxonomic controversy and near-monotypic genera. The clade is reviewed via a new molecular phylogenetic analysis and those results are combined with brief reconsideration of morphology in the group, aiming to rationalize the species into a smaller number of larger monophyletic genera and sections. Nuclear ribosomal internal transcribed spacer (ITS) sequences were obtained from 86 accessions of 35 named taxa, supplemented from GenBank with five accessions encompassing a further two named taxa. Using Pseudorchis as outgroup, and scoring indels, the data matrix generated 30 most-parsimonious trees that differed in the placement of two major groups plus two closely related species. Several other internal nodes also attracted only indifferent statistical support. Nonetheless, by combining implicit assessment of morphological divergence with explicit assessment of molecular divergence (when available), nine former genera can be rationalized into four revised genera by sinking the monotypic Amerorchis, together with Aceratorchis and Chondradenia (neither yet sequenced), into Galearis, and by amalgamating Piperia, Diphylax and the monotypic Tsaiorchis into the former Platanthera section Platanthera. After further species sampling, this section will require sub-division into at least three sections. The present nomenclatural adjustments prompt five new combinations. Resolution of major groups should facilitate future species-level research on the Platanthera clade. Recent evidence suggests that ITS sequence divergence characterizes most species other than the P. bifolia group. The floral differences that distinguished Piperia, Diphylax and Tsaiorchis from Platanthera, and Aceratorchis and Chondradenia from Galearis, reflect various forms of heterochrony (notably paedomorphosis); this affected both the perianth and the gynostemium, and may have proved adaptive in montane habitats. Floral reduction was combined with lateral expansion of the root tubers in Piperia and Diphylax (including Tsaiorchis), whereas root tubers were minimized in the putative (but currently poorly supported) Neolindleya-Galearis clade. Allopolyploidy and/or autogamy strongly influenced speciation in Platanthera section Limnorchis and perhaps also Neolindleya. Reproductive biology remains an important driver of evolution in the clade, though plant-pollinator specificity and distinctness of the species boundaries have often been exaggerated.


Finding significance: New perspectives in variant classification of the RAD51 regulators, BRCA2 and beyond.
For many individuals harboring a variant of uncertain functional significance (VUS) in a homologous recombination (HR) gene, their risk of developing breast and ovarian cancer is unknown. Integral to the process of HR are BRCA1 and regulators of the central HR protein, RAD51, including BRCA2, PALB2, RAD51C and RAD51D. Due to advancements in sequencing technology and the continued expansion of cancer screening panels, the number of VUS identified in these genes has risen significantly. Standard practices for variant classification utilize different types of predictive, population, phenotypic, allelic and functional evidence. While variant analysis is improving, there remains a struggle to keep up with demand. Understanding the effects of an HR variant can aid in preventative care and is critical for developing an effective cancer treatment plan. In this review, we discuss current perspectives in the classification of variants in the breast and ovarian cancer genes BRCA1, BRCA2, PALB2, RAD51C and RAD51D.


Immunoreactivity of glycoproteins isolated from human peripheral nerve and Campylobacter jejuni (O:19).
Antibodies to ganglioside GM1 are associated with Guillain-Barré Syndrome (GBS) in patients with serologic evidence of a preceding infection with Campylobacter jejuni. Molecular mimicry between C. jejuni Lipopolysaccharide (LPS) and ganglioside GM1 has been proven to be the immunopathogenic mechanism of the disease in the axonal variant of GBS. GM1-positive sera cross-react with several Gal-GalNAc-bearing glycoproteins from the human peripheral nerve and C. jejuni (O:19). This study aimed to examine the immunoreactivity of the digested cross-reactive glycoproteins isolated from the human peripheral nerve and C. jejuni (O:19) with Peanut Agglutinin (PNA) as a marker for the Gal-GalNAc determinant, and with sera from patients with GBS. For this purpose, the cross-reactive glycoproteins from peripheral nerve and C. jejuni (O:19) were enzymatically digested with trypsin and the obtained peptides were incubated with PNA and GBS sera. Western blot analysis of the separated peptides revealed several bands showing positive reactivity to PNA and to sera from patients with GBS, present in both digests from peripheral nerve and C. jejuni (O:19). These data indicate the possible molecular mimicry between the cross-reactive glycoproteins present in C. jejuni and human peripheral nerve and its potential role in the development of GBS following infection with C. jejuni (O:19).


Can the need for colectomy after computed tomography-guided percutaneous drainage for diverticular abscess be predicted?
The primary aim of this study was to define predictors of computed tomography (CT)-guided percutaneous abscess drainage treatment failure in complicated diverticulitis. A 10-year retrospective analysis of inpatients seen in surgical consultation for diverticular abscess management subsequently referred for CT-guided percutaneous drainage (PD) was conducted. The clinical courses of patients undergoing a technically successful PD were categorized into three groups: 1) no colectomy; 2) elective colectomy; and 3) nonelective colectomy. Forty study patients were identified. Thirteen (33%) of the 40 patients required a nonelective colectomy, 20 patients (50%) underwent elective resection, and seven patients (18%) have been managed nonoperatively with no recurrent diverticulitis for a median of 46.8 months (range, 3.2 to 84.3 months). Forward logistic regression identified the presence of immunosuppression or renal insufficiency (creatinine 1.5 mg/dL or greater) as factors independently associated with failure of PD and need for nonelective colectomy. No clinical, laboratory, or radiologic variables were predictive of long-term nonoperative success. Although PD allows for the resolution of intra-abdominal sepsis for most cases of diverticulitis complicated by an abscess, a substantial proportion progress to nonelective colectomy, emphasizing the need for clinical vigilance in follow-up.


Methods of studying antihistamines.
A variety of ingenious methods have been devised to challenge and incite episodes of acute allergic rhinitis in susceptible individuals. These methods teach us much about basic mechanisms involved in the disease. There is some danger in using them for efficacy trials because antihistamines are only partially effective treatment for hay fever and the challenge administered could easily overcome the degree of protection. Additional studies may lead to a better understanding of the factors involved in challenges and hence, their usefulness in clinical testing. The out-patient trial design is successful in demonstrating efficacy in 40 to 60 per cent of trials. The field trial is 70 to 90 percent accurate in its findings. The clinical design of antihistamine trials has improved remarkably in the past 10 years. Because of the nature of the disadvantages discussed throughout this report, I would doubt that further improvements in design will occur in future years unless a substitute is found for subjective evaluations.


Trajectory of cognitive decline as a predictor of psychosis in early Alzheimer disease in the cardiovascular health study.
To compare the trajectories of cognitive decline between groups with, and without, the later development of psychotic symptoms during Alzheimer disease (AD) or mild cognitive impairment (MCI). : The authors examined cognitive function in a new analysis of an existing data set, the Cardiovascular Health Study, an epidemiologic, longitudinal follow-up study. Our analyses examined 9 years of follow-up data. Community. The authors examined subjects who were without dementia at study entry, received a diagnosis of AD or MCI during follow-up, and had been rated on the Neuropsychiatric Inventory for the presence of psychosis; 362 participants for the modified Mini-Mental State Examination (3MS) analysis and 350 participants for the digit symbol substitution test (DSST) analysis had sufficient follow-up data and apolipoprotein-∊ (APOE) genotyping. The 3MS and DSST were administered annually and analyzed using mixed-effects models including APOE4 status. : Mean 3MS and DSST scores did not differ between AD with psychosis (AD + P) and without psychosis groups at baseline. The 3MS and DSST scores decreased more rapidly in subjects who ultimately developed psychosis. Individuals who ultimately develop psychosis have more rapid cognitive deterioration during the earliest phases of AD than individuals with AD not developing psychosis. The genetic and other neurobiologic factors leading to the expression of AD + P may exert their effects by acceleration of the neurodegenerative process.


Layered-metal-hydroxide nanosheet arrays with controlled nanostructures to assist direct electronic communication at biointerfaces.
In this work, ordered vertical arrays of layered double hydroxide (LDH) nanosheets have been developed to achieve electron transfer (eT) at biointerfaces in electrochemical devices. It is found that tailoring the gap size of LDH nanosheet arrays could significantly promote the eT rate. This research has successfully extended nanomaterials for efficient modifications of electrode surfaces from nanoparticles, nanowires, nanorods, and nanotubes to nanosheets.


Characteristics of [3H]GBR 12935 binding in the human and rat frontal cortex.
Binding characteristics of the selective dopamine uptake inhibitor [3H]GBR 12935 have been described for the striatum but not for the frontal cortex. We have developed assay conditions for quantifying [3H]GBR 12935 binding in the frontal cortex. In both the rat and human frontal cortex, the assay required four times more tissue (8 mg/ml) than in the striatum (2 mg/ml). [3H]GBR 12935 binding in the frontal is complex, as it involves multiple binding sites. The high-affinity binding site is sodium dependent and is inhibited by sodium. In human but not in rat frontal cortex, addition of K+ reversed the sodium inhibition. The pharmacological profile of the high-affinity [3H]GBR 12935 binding site is consistent with that of the dopamine transporter, because drugs with the most selective dopamine reuptake blocking activities are the most potent displacers of [3H]GBR 12935 binding. There is a positive correlation between the rat and human inhibitory constants, a finding indicating that there are similar pharmacological profiles across at least these two species. Rats with a 6-hydroxydopamine lesion had a 47% decrease in number of [3H]GBR 12935 binding sites, a result indicating that at least a portion of these sites had been on presynaptic dopamine terminals.


Early adolescent cannabis exposure and positive and negative dimensions of psychosis.
To investigate the effect of exposure to cannabis early in adolescence on subclinical positive and negative symptoms of psychosis. Cross-sectional survey in the context of an ongoing cohort study. Government-supported general population cohort study. A total of 3500 representative 19-year olds in Greece. Subjects filled in the 40-item Community Assessment of Psychic Experiences, measuring subclinical positive (paranoia, hallucinations, grandiosity, first-rank symptoms) and negative psychosis dimensions and depression. Drug use was also reported on. Use of cannabis was associated positively with both positive and negative dimensions of psychosis, independent of each other, and of depression. An association between cannabis and depression disappeared after adjustment for the negative psychosis dimensions. First use of cannabis below age 16 years was associated with a much stronger effect than first use after age 15 years, independent of life-time frequency of use. The association between cannabis and psychosis was not influenced by the distress associated with the experiences, indicating that self-medication may be an unlikely explanation for the entire association between cannabis and psychosis. These results add credence to the hypothesis that cannabis contributes to the population level of expression of psychosis. In particular, exposure early in adolescence may increase the risk for the subclinical positive and negative dimensions of psychosis, but not for depression.


Azelaic acid. A review of its pharmacological properties and therapeutic efficacy in acne and hyperpigmentary skin disorders.
Azelaic acid is a naturally occurring saturated dicarboxylic acid which, on topical application (usually as a 20% cream), has been shown to be effective in the treatment of comedonal acne and inflammatory (papulopustular, nodular and nodulocystic) acne, as well as various cutaneous hyperpigmentary disorders characterised by hyperactive/abnormal melanocyte function, including melasma and, possibly, lentigo maligna. In addition, azelaic acid has an antiproliferative and cytotoxic effect on the human malignant melanocyte, and preliminary findings indicate that it may arrest the progression of cutaneous malignant melanoma. The mechanism of this selective cytotoxic action of azelaic acid is unclear, but may possibly be related to its inhibition of mitochondrial oxidoreductase activity and DNA synthesis. In controlled studies, topical azelaic acid demonstrated comparable anti-acne efficacy to topical tretinoin, benzoyl peroxide, erythromycin and oral tetracycline, while in patients with melasma azelaic acid proved at least as effective as topical hydroquinone. On topical application azelaic acid is well tolerated, with adverse effects apparently limited to a generally mild and transient local cutaneous irritation. Thus, topical azelaic acid, employed either as monotherapy or in combination with other treatments, is likely to prove of value in the management of acne and several hyperpigmentary disorders, most notably melasma.


Primary CNS lymphoma in Immunocompetent patients: Appearances on Conventional and Advanced Imaging with Review of literature.
Primary central nervous system lymphoma (PCNSL) constitutes about 3% of all primary brain tumors and nearly 1 to 3% of all Non Hodgkin Lymphomas. In the recent years the incidence of primary CNS lymphoma is increasing in immunocompetent patients. As PCNSL are chemosensitive as well as radiosensitive, its early and accurate diagnosis is imperative for optimal management. Contrast enhanced Magnetic Resonance Imaging (MRI) is the recommended imaging modality for PCNSL; however, contrast enhanced Computed Tomography (CE-CT) is done in cases where MRI is contraindicated. Advanced imaging techniques like DWI (diffusion weighted imaging), MRS (MR Spectroscopy), MR perfusion, DTI (Diffusion tensor imaging) are important in diagnosis and help in its differentiation from other tumors.


Tools and Methods for Investigating Synthetic Metal-Catalyzed Reactions in Living Cells.
Although abiotic catalysts are capable of promoting numerous new-to-nature reactions, only a small subset has so far been successfully integrated into living systems. Research in intracellular catalysis requires an interdisciplinary approach that takes advantage of both chemical and biological tools as well as state-of-the-art instrumentations. In this perspective, we will focus on the techniques that have made studying metal-catalyzed reactions in cells possible using representative examples from the literature. Although the lack of quantitative data in vitro and in vivo has somewhat limited progress in the catalyst development process, recent advances in characterization methods should help overcome some of these deficiencies. Given its tremendous potential, we believe that intracellular catalysis will play a more prominent role in the development of future biotechnologies and therapeutics.


Ideal entry point and trajectory for C2 pedicle screw placement in children: a 3D computed tomography study.
To identify the ideal entry point for pediatric C2 pedicle screw and to obtain parameters of it for the indication of pediatric atlantoaxial fusion arthrodesis. The pediatric cervical CT images were reconstructed into the 3D digital models and the C2 vertebrae were separated. The location of ideal entry point and screw placement related linear and angular parameters were assessed on the 3D digital models. A total of 214 pedicles from 107 C2 digital models were analyzed. The average entry point for C2 was 3.80 ± 2.78 mm medial to the lateral notch (LN) and 2.57 ± 1.70 mm superior to the LN. The average pedicle diameter (PD) was 6.02 ± 1.31 mm, and the average pedicle screw length (PSL) was 25.63 ± 3.46 mm. Statistical differences were found between different sex for PD and PSL (P < 0.05). As patient age increases, using the most lateral and inferior edge of the lateral mass as a reference marker, the entry point tends to move medial and cephalad, when using the LN as a reference marker, the entry point tends to move medial and slightly caudad. Univariate linear regression analysis suggested that these linear parameters were associated with age (P < 0.01). In this study, we found that the measurement results of C2 pedicle screw varied based on sex, laterality, and ages for children younger than 18 years. The entry point of the screws facilitating ideal trajectory tends to change in a linear way as a function of age. This information helps the surgeon to establish the specific anatomy related to C2 pedicle screw placement to facilitate fixation in the pediatric patients.


Transforming growth factor-alpha (TGF alpha) concentrations increase in regenerating rat liver: evidence for a delayed accumulation of mature TGF alpha.
Changes in the concentration of transforming growth factor-alpha (TGF alpha) protein were measured in regenerating liver. TGF alpha stimulates both DNA and protein synthesis in various liver-derived cells, and its mRNA levels increase in liver after partial hepatectomy (PH), suggesting that it may be an important autocrine regulator of liver regeneration. Using a sheep antiserum raised against mature rat TGF alpha, we developed a sensitive TGF alpha RIA. TGF alpha was extracted from livers in a detergent-containing buffer with protease inhibitors. Liver extracts, to a volume of 10 microliters/tube, produced a displacement curve of [125I]TGF alpha that was parallel to the pure standard. The TGF alpha content of normal liver was 57.04 +/- 26.25 pg/mg protein, 5.24 +/- 2.61 ng/mg DNA, and 10.33 +/- 4.47 ng/g liver (n = 5; mean +/- SD). Between 13-17 h after operation, TGF alpha concentrations in the livers of PH animals increased over those in sham-operated (SH) controls (P < 0.05) and remained twice those in SH controls for more than 96 h, returning to control values by 8 days. In unoperated liver, gel chromatography showed all TGF alpha immunoactivity to be in fractions corresponding to known TGF alpha precursors (15-30 kilodaltons). Mature 5.6-kilodalton TGF alpha was not detected until 48 h after PH and was still present at 96 h. These data support a role for TGF alpha in the response to PH in the rat. However, the presence of TGF alpha precursors in normal liver, the short (< 4-h) interval between the increase in TGF alpha concentrations and the onset of hepatocyte DNA synthesis, the sustained elevation of TGF alpha levels after DNA synthesis has ceased, and the lack of detectable processing to the mature form until DNA synthesis has subsided all suggest that the membrane-anchored precursor and the mature forms of TGF alpha may have different functions, cellular sources, or target cells in regenerating liver.


Maxillofacial Trauma and COVID-19: A Review of the First 6 Months of the Pandemic.
Retrospective cohort study. The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in late December 2019 has spread globally resulting in a pandemic of respiratory illness. The purpose of this study is to understand the impact of the first 6 months of the COVID-19 pandemic on the epidemiology of maxillofacial trauma at an urban trauma center. The study sample was derived from the population of patients who presented for evaluation and management of maxillofacial injuries at TriStar Skyline Medical Center in Nashville, Tennessee beginning March 1, 2020 and ending August 31, 2020, compared to the same period in 2019. Descriptive and bivariate statistics were calculated for study variables in each cohort with significance set at P < .05. The number of subjects in the 2020 cohort (n = 212) was 4.2% higher than the 2019 cohort (n = 203). Volume decreased 24.5% during the initial phase of the pandemic with a 36.1% increase in volume occurring during the reopening phase (P = .003). Volume related to interpersonal decreased 52.4% during the initial phase of the pandemic with a rebound increase of 30% during reopening (P = .005). The first case of COVID-19 presented in Nashville, Tennessee in early March 2020. Over the next 6 months, periods of lockdown and reopening transpired. The volume of maxillofacial trauma decreased during the initial 3-months of the pandemic and rebounded to volumes greater than the year prior.


Knowledge and practice pattern of non-allopathic indigenous medical practitioners regarding tuberculosis in a rural area of India.
To assess the knowledge and practice patterns of non-allopathic indigenous medical practitioners (IMPs) regarding tuberculosis (TB). Seventy-four IMPs practising in Naraingarh block, a rural area of Haryana State, India, were interviewed using a semi-structured interview schedule. Fifty-four per cent (40/74) of the IMPs saw two to five TB patients every month. Sixty-one per cent (46/74) reported that they based their diagnosis of TB on symptoms alone, whereas 38% use diagnostic tests such as chest X-ray, erythrocyte sedimentation rate and sputum examination. Forty per cent of the IMPs reported that alcohol was the cause of TB, 36.5% cited smoking and 17.6% reported infection as the cause. Only 34% (25/74) of IMPs reported that they treated TB patients, while the rest said that they referred such cases to nearby hospitals. Anti-tuberculosis drugs used by IMPs were isoniazid, rifampicin and streptomycin, but none of them knew the dosage of the drugs, the duration of treatment or the correct regimen. Sixty-four per cent of the 25 IMPs reported using ayurvedic medicines. Considerable proportions of TB patients seek IMPs for cure of TB, while the knowledge and practice of IMPs is inadequate.


Oral Health Education in Children before Dental Treatment under General Anesthesia.
The aim of this study was to evaluate the attitude of parents towards the oral health of their children before oral rehabilitation under general anesthesia (GA). Children receiving dental treatment under GA between November 2013 and July 2014 in the Pediatric Dentistry Department (University Hospital Center, Toulouse, France) were enrolled in an oral health preventive program. An anonymous questionnaire was self-administered by the parents during the pre-operative session. The sample comprised 67 children with a mean age of 4.8 years. 48 % of the parents had difficulties in maintaining the oral hygiene of their child. Two thirds of them reported a lack of cooperation. An adult cleaned the child's teeth in 43% of the cases. 14% of the study population brushed their teeth twice a day or more. In addition, half of the parents reported that they modified food consumption or teeth cleaning habits of their children since the initial consultation. This study suggests a low compliance of parents and children with the recommendations on oral hygiene and food consumption given at the initial visit and demonstrates the feasibility of a preventive program in this population.


Bronchial responsiveness to methacholine: relation to respiratory symptoms and pulmonary function.
A methacholine bronchial provocation test was administered to 290 subjects obtained from the 1,900 male volunteers participating in the Normative Aging Study. A positive response (less than 20% decline in FEV1) was obtained in 83 subjects. A positive response was associated with current smoking, presence of wheeze and reduced FEV1. Bronchial responsiveness, cigarette smoking, normal subjects, FEV1.


Ultrasound guided aspiration biopsy of peripheral pulmonary lesions.
Forty-six patients with peripheral lung lesions underwent ultrasound-guided percutaneous needle aspiration biopsy. Aspirates were sent for cytological and/or microbiological examination. Confirmative diagnosis was obtained in 40 patients (86.9%). Twenty-eight patients had positive cytology for malignancy and 12 patients with benign lesions had diagnosis made by cytologic and microbiologic examination. None of the lesions could be diagnosed by sputum cytology and fibreoptic bronchoscopy with biopsy or brushings. No complication was observed in any patient. We conclude that ultrasound guided aspiration biopsy is a useful and safe method for the diagnosis of peripheral pulmonary masses. The diagnostic yield far exceeds that which can be obtained by sputum cytology and fibreoptic bronchoscopy with biopsy.


The use of RNA/DNA ratio measurements to assess rifampicin-induced growth inhibition of Escherichia coli.
Growth rates and cellular levels of RNA, DNA and protein were studied in Escherichia coli during and following exposure to rifampicin, and in the transition from stationary to exponential phase growth in drug-free medium. At rifampicin concentrations of up to twice the MIC, significant changes in growth rates were only apparent after several generations. At higher rifampicin concentrations growth was terminated much more rapidly. In every case changes in growth rates were closely paralleled by corresponding changes in RNA/DNA ratios. These findings suggest the possibility of using RNA/DNA ratio measurements to monitor the drug-induced growth inhibition of other bacteria.


Dihydromethysticin kavalactone induces apoptosis in osteosarcoma cells through modulation of PI3K/Akt pathway, disruption of mitochondrial membrane potential and inducing cell cycle arrest.
The objective of the present study was to evaluate the tumor and apoptotic effects of dihydromethysticin kavalactone against human osteosarcoma (MG-63) cells. Antiproliferative activity was measured with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis induction by dihydromethysticin was demonstrated by fluorescence microscopy, quantitative videomicroscopy and Annexin V-FITC apoptosis detection kit. Mitochondrial membrane potential disruption was demonstrated by rhodamine-123 dye using flow cytometry. We also evaluated the effect of dihydromethysticin on PI3K/Akt pathway with an immunoblotting analysis. The results showed that the compound induced dose-dependent as well as time-dependent antiproliferative effects against MG-63 cell growth. Cell death and apoptotic body formation was noticed followed dihydromethysticin treatment at various doses. The percentage of apoptotic cells (early apoptosis+late apoptosis) increased from 6.63% in untreated control to 23.92%, 23.81% and 93.9% in 25 µM, 75 µM and 100 µ Mdihydromethysticin-treated cells respectively. Flow cytometric analysis showed dihydromethysticin induced an increase in G0/G1 cells (apoptotic cells). Furthermore, we observed mitochondrial transmembrane depolarization along with decreased phosphorylation levels for PI3K, AKT (Ser 473), AKT (Thr 308), GSK-3β, and BAD. These reductions were associated with down regulation of AKT and upregulation of both GSK-3β and BAD.


Role of adenoidectomy in otitis media and respiratory function.
Adenoidectomy is among the most frequent surgical procedures performed on children. The rationale for adenoidectomy is to remove a chronically infected or enlarged and obstructing adenoid. Adenoidectomies are performed on children who have recurrent or chronic otitis media with effusion, on children with chronic rhinosinusitis, and on children with nasopharyngeal obstruction causing sleep disturbances and continuous mouth breathing. Various underlying factors that lead to adenoidectomy are also associated with asthma. Asthma is associated with recurrent respiratory tract infections predisposing individuals to recurrent or chronic otitis media and chronic rhinosinusitis. Children with asthma also have an increased risk of sleep-disordered breathing that is treated with adenoidectomy in the presence of nasopharyngeal obstruction. In nonasthmatic children, adenoidectomy does not influence the development of IgE-mediated allergy, bronchial hyperreactivity, or exhaled nitric oxide concentrations, all of which are surrogate asthma markers. Adenoidectomy in selected asthmatic children may relieve comorbidities associated with asthma.


Determinants of routine immunization coverage in Bungudu, Zamfara State, Northern Nigeria, May 2010.
Immunization is a cost-effective public health intervention to reduce morbidity and mortality associated with infectious diseases. The Nigeria Demographic and Health Survey of 2008 indicated that only 5.4% of children aged 12-23 months in Bungudu, Zamfara State were fully immunized. We conducted this study to identify the determinants of routine immunization coverage in this community. We conducted a cross-sectional study. We sampled 450 children aged 12-23 months. We interviewed mothers of these children using structured questionnaire to collect data on socio-demographic characteristics, knowledge on immunization, vaccination status of children and reasons for non-vaccination. We defined a fully immunized child as a child who had received one dose of BCG, three doses of oral polio vaccine, three doses of Diptheria-Pertusis-Tetanus vaccine and one dose of measles vaccine by 12 months of age. We performed bivariate analysis and logistic regression using Epi-info software. The mean age of mothers and children were 27 years (standard error (SE): 0.27 year) and 17 months (SE: 0.8 month) respectively. Seventy nine percent of mothers had no formal education while 84% did not possess satisfactory knowledge on immunization. Only 7.6% of children were fully immunized. Logistic regression showed that possessing satisfactory knowledge (Adjusted OR=18.4, 95% CI=3.6-94.7) and at least secondary education (Adjusted OR=3.6, 95% CI=1.2-10.6) were significantly correlated with full immunization. The major determinants of immunization coverage were maternal knowledge and educational status. Raising the level of maternal knowledge and increasing maternal literacy level are essential to improve immunization coverage in this community.


Polysaccharide Cryogels Containing β-Cyclodextrin for the Delivery of Cannabidiol.
Cannabidiol (CBD) has attracted increasing interest due to its therapeutic potential for treating numerous diseases. However, CBD is very lipophilic and has very unfavorable pharmacokinetics and low bioavailability. Efforts are focused on developing drug delivery systems for enhanced solubilization and therapeutic activity of CBD. Here, we report the preparation of original super-macroporous cryogels from 2-hydroxyethyl cellulose (HEC) and β-cyclodextrin (β-CD) designed for the topical delivery of CBD. The cryogels were synthesized by photochemical crosslinking in a frozen aqueous system, purified, and then loaded with CBD. The effect of HEC/β-CD mass ratio (100:0; 50:50; 40:60 and 20:80) in the reaction mixture on the reaction efficiency, physico-mechanical properties of cryogels, drug release profile, and antineoplastic potential were evaluated in detail. The cryogels showed a bi-phasic release behavior: initial burst release in the first 3 hours followed by slower drug release which can be beneficial in the treatment of cutaneous neoplastic diseases.


Simultaneous determination of benzophenone-type UV filters in water and soil by gas chromatography-mass spectrometry.
A novel method has been developed to simultaneously determine and quantify seven organic UV filters employing liquid (solid)-liquid extraction, derivatization with N-methyl-N-(trimethylsilyl) trifluoroacetamide (MSTFA) and gas chromatography with mass spectrometric detection in various environmental matrices. The UV filters determined were: benzophenone (BP), benzhydrol (BH), 4-hydroxybenzophenone (HBP), 2-hydroxy-4-methoxybenzophenone (HMB), 2,4-dihydroxybenzophenone (DHB), 2,2'-dihydroxy-4-methoxybenzophenone (DHMB) and 2,3,4-trihydroxylbenzophenone (THB). Under optimal conditions, the analysis required 23 min and good linearity over the range of 10-2,500 ng/L in water and 100-25,000 ng/kg in soil for each UV filter obtained. The high recovery (62-114% and 60-125% for water and soil samples, respectively) and the low RSD values (less than 13.9 and 17.2% for water and soil samples, respectively) indicated the high performance of this method. The method detection limits (MDLs) were relatively low, ranging from 5 to 100 ng/L or kg and quantification limits ranged between 25 and 500 ng/L or kg for all test compounds. This validated method was applied in the analysis of seven BP-type UV filters collecting water and soil samples in Korea, between April and May 2003. The overall concentration of UV filters in the soil sample (500-18,380 ng/kg) was highly distributed in water sample (27-204 ng/L). The established method was successfully applied to monitor the residue measurement of the BP-type UV filters in environmental water and soil samples.


Detection of Helicobacter pylori in gastric cancer.
Considering the high prevalence of stomach cancer in the northern region of Brazil and the recognized relationship between chronic gastric inflammation caused by Helicobacter pylori, and its carcinogenic potential, the objective we had with this study was to investigate the presence of the microorganism in macro and microscopic presentations of neoplasm in different regions of the stomach, and in non-malignant lesions concomitant to the adenocarcinoma in patients originating from the metropolitan area of Belém (State of Pará, Brazil). Examinations were made on 172 patients divided into two groups: group I, formed by 75 patients with gastric carcinoma, and group II, formed by 97 patients with mild enanthematic gastritis, considered control group. The diagnosis was obtained during endoscopic examination and the respective biopsy. Gastric neoplasms were classified macroscopically in accordance with Borrmann's classification, and microscopically in accordance with Laurén's classification. In group I, 54 patients were male and 21 female while in group II, 22 patients were male and 75 female. The average age in group I was 61.2 years (range 27 to 86 years), while in group II it was 37.5 years (range 16 to 69 years). Thin sections were prepared and stained using the hematoxylin-eosin method. In the Helicobacter pylori research, the modified Gram stain was utilized. Statistical analysis was done by utilizing the chi-squared (chi 2) test, Mann-Whitney test (U), and Fisher's exact test. The results showed the detection of Helicobacter pylori were significantly greater in patients with mild enanthematic gastritis than in patients with gastric carcinoma. The presence of Helicobacter pylori in patients with gastric carcinoma and mild enanthematic gastritis was significantly greater in the antral region than in other gastric regions. Helicobacter pylori detection in patients with gastric carcinoma did not present a significant difference in relation to the macroscopic aspect of the tumor either intestinal or diffuse histological types. These data suggest the presence of the bacteria is predominant in the antral region and it does not show relation with the macroscopic types or histological intestinal or diffuse types of gastric carcinoma.


[Fluorescence spectroscopy characterization of asphaltene liquefied from coal and study of its association structure].
Structure and association of asphaltenes from coal direct hydroliquefaction were studied by fluorescence spectrometry and UV-Vis absorption spectrometry in this paper. The results indicate that asphaltene is aromatic mixtures mainly containing naphthalene nucleus and shows strong fluorescent characteristic. The forming of exciplex between asphaltene and solvent results in the red shift of fluorescence peak and fluorescence quenching of asphaltene that increases with the polarity and electron acceptability. The self-aggregation of asphaltene is formed by non-covalent bond interaction, so that the asphaltene liquefied at higher temperture that shows high aromaticity has stronger association than that liquefied at lower temperature. Aggregation of asphaltene has been found to be a gradual process, in which there is no critical aggregation constant observed, and the inflection point of the plot of apparent fluorescence intensity as a function of asphaltene concentration varies with the excitation wavelength.


Increasing Campylobacter Infections, Outbreaks, and Antimicrobial Resistance in the United States, 2004-2012.
Campylobacteriosis, a leading cause of foodborne illness in the United States, was not nationally notifiable until 2015. Data describing national patterns and trends are limited. We describe the epidemiology of Campylobacter infections in the United States during 2004-2012. We summarized laboratory-confirmed campylobacteriosis data from the Nationally Notifiable Disease Surveillance System, National Outbreak Reporting System, National Antimicrobial Resistance Monitoring System, and Foodborne Diseases Active Surveillance Network. During 2004-2012, 303520 culture-confirmed campylobacteriosis cases were reported. Average annual incidence rate (IR) was 11.4 cases/100000 persons, with substantial variation by state (range, 3.1-47.6 cases/100000 persons). IRs among patients aged 0-4 years were more than double overall IRs. IRs were highest among males in all age groups. IRs in western states and rural counties were higher (16.2/100000 and 14.2/100000, respectively) than southern states and metropolitan counties (6.8/100000 and 11.0/100000, respectively). Annual IRs increased 21% from 10.5/100000 during 2004-2006 to 12.7/100000 during 2010-2012, with the greatest increases among persons aged >60 years (40%) and in southern states (32%). The annual median number of Campylobacter outbreaks increased from 28 in 2004-2006 to 56 in 2010-2012; in total, 347 were reported. Antimicrobial susceptibility testing of isolates from 4793 domestic and 1070 travel-associated infections revealed that, comparing 2004-2009 to 2010-2012, ciprofloxacin resistance increased among domestic infections (12.8% vs 16.1%). During 2004-2012, incidence of campylobacteriosis, outbreaks, and clinically significant antimicrobial resistance increased. Marked demographic and geographic differences exist. Our findings underscore the importance of national surveillance and understanding of risk factors to guide and target control measures.


Antibody-induced alterations of Na+/K(+)-ATPase activity in rabbit red blood cells during experimental thyroglobulin immunization.
Thyroid hormone modulates cell membrane Na+/K(+)-ATPase. A detailed study of erythrocyte membrane Na+/K(+)-ATPase activity was carried out during experimental thyroglobulin immunization. During the process of immunization there was a sharp decline in Na+/K(+)-ATPase activity until the 98th day of immunization, when the thyroglobulin antibody titer was at its peak. This enzyme activity retained a lower level although a fall in antibody titer occurred up to the 147th day.


Johann Jakob Wepfer (1620-1695): A review of his contributions to neuropsychology on the quadricentennial of his birth.
The effects of brain damage on behavior have been reported by authors from the Greek, Roman, Medieval, Renaissance, and seventeenth-century medical traditions. However, few of the reported cases discussed mind-brain relationships, even fewer reported data that offered a description of cognitive functions, and none described a clear association of a functional mechanism of cognitive impairment with identifiable focal brain damage. An exception is found in the case studies by Johann Jakob Wepfer (1620-1695). After reviewing the pre-seventeenth-century background and Wepfer's milieu, we analyze his texts on neuroanatomy, apoplexy, and brain vascularization (Observationes anatomicae ex cadaveribus eorum, quos sustulit apoplexia cum exercitatione de ejus loco affecto) and his remarkable collection of 222 neurological cases (Observationes medico-practicae de affectibus capitis internis & externis), posthumously published in 1727. We focus on his reports concerning on the presence of aphasia, memory disorders, and unilateral neglect, correlated with focal brain damage, with particular emphasis on his examination of language impairments.