Pseudomonas hyperimmune globulin passive immunotherapy for pulmonary exacerbations in cystic fibrosis.
We studied the effect of an intravenously administered gamma globulin [Ps-ivIG] enriched fivefold over conventional ivIG for Pseudomonas aeruginosa lipopolysaccharide [PA LPS] antibodies on ten patients with cystic fibrosis [CF] aged 19-32 years during hospitalization for pulmonary deterioration. All were colonized with greater than or equal to 1 PA phenotype resistant to all antibiotics at the time of admission and they received 500 mg/kg Ps-ivIG intravenously as a single dose in addition to conventional treatment, including antibiotics and chest physiotherapy. No adverse effects occurred. Circulating immune complexes and complement levels remained unchanged from baseline. Serum levels of anti-PA LPS IgG, as measured by ELISA for eight PA LPS immunotypes, increased to 244 +/- 65% (mean +/- SE) of baseline levels 1 hour post-infusion (P less than 0.01), remained significantly elevated during a mean hospital stay of 17 days, and returned to near baseline by follow-up 4 weeks after hospital discharge. Plasma half-life and clearance values were similar to those of other subjects receiving conventional ivIG. Sputum PA density declined from 3.0 to 1.2 x 10(8) cfu/mL 1 week post-infusion (P approximately equal to 0.05), and returned to baseline at follow-up. Serum anti-PA opsonic activity increased after infusion (P less than 0.01), but returned to baseline by 72 hours. Clinical scores improved from admission to discharge (P less than 0.005) without decline at follow-up. Forced vital capacity [FVC] and forced expiratory volume in one second [FEV1] increased from admission to discharge (P less than 0.01 and P less than 0.05, respectively) without decline at follow-up. Using autologous historical control data, standard hospital therapy without Ps-ivIG resulted in no improvement in FVC or FEV1, and a subsequent decline in these parameters (P less than 0.05 for each) during a similar follow-up period. This occurred despite the fact that half the patients did not have antibiotic-resistant PA on the control admission. We conclude that Ps-ivIG is a safe adjunctive therapy for pulmonary exacerbations in moderately ill cystic fibrosis patients colonized with resistant PA, and may be associated with both greater and more prolonged improvement in pulmonary function than standard therapy alone.


Algesiogenic and analgesic activities of synthetic substance P.
The objective of our study was to determine whether the pure synthetic substance P(SP) is algesiogenic or analgesic when administered centrally or peripherally. The relationships between SP-induced analgesia and the content of morphine-like factor (MLF) in the brain were also studied. Intracarotid arterial administration of SP (20-200 microgram) produced no pseudoaffective responses to pain in six out of nine rats, but in the remaining three, there was an exhibition of these responses. Chlorpheniramine pretreatment antagonized these responses. On cantharidin blister base experiments in humans, SP (10(-3) g/ml) produced slight pain and an itchy sensation. SP given intracerebroventricularly produced an analgesia in mice in a dose of 5 ng/mouse, as determined by the acetic acid-induced writhing and hot plate methods. These SP-induced analgesia were antagonized by naloxone pretreatment. SP did not alter the content of MLF in the mouse whole brain. However, SP5-11 not only produced an analgesia but also increased the content of MLF. These results suggest that SP has a slight algesiogenic activity which might be mediated by histamine and a slight analgesic activity which might be mediated by MLF.


Clinical Characteristics, Outcomes, and Progression to Type 2 Diabetes in Women with Hyperglycemia in Pregnancy.
Women with hyperglycemia in pregnancy (HIP) are at increased risk of developing type 2 diabetes (T2D). The present study intended to study the incidence of postpartum diabetes among HIP women and predict its risk factors. This was a prospective observational study done on 178 women with HIP diagnosed after the first trimester, attending the tertiary care hospitals between December 2018 and March 2020. Demographics, clinical variables, and feto-maternal outcomes were recorded. The postpartum glycemic status was determined using a 75 g oral glucose tolerance test (OGTT) at 1 and 6 months. All analyses were performed with SPSS software (version 21.0). The mean age of women with HIP was 30.2 ± 6.1 years, with 38% having a family history of diabetes. Eighty percent of the women delivered full-term babies and 71.3% underwent a cesarean section. Gestational hypertension was present in 21.9% of patients. Macrosomia was present in 4.6% of the babies, hypoglycemia in 6.7%, and spontaneous abortion occurred in 7.7%. Postpartum OGTT at 6 months was completed by 76.4% of participants. The incidence of diabetes and glucose intolerance postpartum was 11.7 and 16.2%, respectively at 6 months. Logistic regression analysis showed that maternal obesity, diagnosis of HIP at an earlier trimester (<24 weeks), need for insulin treatment during pregnancy, signs of insulin resistance and fasting and 2-h plasma glucose >100 (>5.6 mmol/L) and >195 mg/dL (>10.9 mmol/L), respectively, and glycated hemoglobin > 6.5% (>48 mmol/mol) increased the risk of having postpartum diabetes significantly. The incidence of postpartum glucose intolerance in women with HIP is high. Prospective diabetes evaluation is required and intervention should be considered in women with HIP who have obesity, diagnosis of HIP at an earlier trimester, signs of insulin resistance, and require insulin treatment during pregnancy.


Mild Cognitive Impairment with a High Risk of Progression to Alzheimer's Disease Dementia (MCI-HR-AD): Effect of Souvenaid® Treatment on Cognition and 18F-FDG PET Scans.
Previous studies have shown that Souvenaid (medical food) can have benefits on memory, cognition, and function in early Alzheimer's disease (AD) and mild cognitive impairment (MCI). Demonstrate that Souvenaid could improve or maintain cognition and has an effect on neurodegeneration biomarkers. This cohort study was carried out from June 2015 through December 2016 in the Neurology Department, Infanta Cristina Hospital, Madrid, Spain. MCI-HR-AD were recruited using Petersen criteria, neuropsychology (NPS), and 18F-FDG PET scans to confirm the high risk of progression to dementia with one year of follow-up. Age, sex, vascular risk factors (VRF), and NPS values (Barcelona brief version) were analyzed. 18F-FDG PET scans were analyzed as a visual procedure. The study was approved by the Research Committee of ICH. Statistical analysis was made with SPSS 22.0 version. Subjects included 43 MCI patients (58.5% women; mean age 69.78±7.89): 17 receiving Souvenaid® treatment (ST), 24 receiving no treatment (WT) and 2 who withdrew. No differences were seen in VRF, only hypercholesterolemia, and were less prevalent in the ST group (p = 0.002). The rate of progression to dementia was 48.8% (no differences between groups, p = 0.654). A second round of 18F-FDG PET scans showed a significance worsening of glucose metabolism in WT (p = 0.001) versus ST, in which it was low (p = 0.050). For NPS testing, there was a significant worsening in memory performance in the WT group (p = 0.011) and a stabilization in ST (p = 0.083), as well as in executive functions and attention (worsening in WT, p = 0.014). For the Subjective Changing Scale (SCS), caregivers indicated a stabilization/improvement in ST (p = 0.017). Souvenaid had a significant effect on several cognitive domains, and on SCS in patients with MCI-HR-AD. Its intervention had an impact on preservation on 18F-FDG PET scans.


[Value of magnetic resonance tomography prior to surgery and irradiation of peripheral soft tissue tumors].
The experience with magnetic resonance imaging (MRI) of 37 patients with peripheral soft tissue tumours and tumour-like lesions is reported. MRI proved to be a highly sensitive method in detecting soft tissue tumours. The main advantages of MRI compared to CT were the high contrast resolution of MRI and the multiplanar display. The anatomic setting of the soft parts tumour could be defined in most cases as either intracompartmental or extracompartmental. The relationship to the major neurovascular bundles and bone could be assessed accurately. Tumour-induced subtle periosteal reactions and cortical erosions are better defined with CT and plain film, especially. An imaging technique using small excitation angles, echoes produced by gradient inversion and extremely fast repetition times ("Fast Field Echo Imaging") is capable of producing MR images in only a few seconds acquisition time. Preliminary experience shows that soft tissue tumours can be evaluated with this rapid pulse sequence.


Long-Term Efficacy and Tolerability of a Medium G' HA Filler with Tri-Hyal Technology on the Rejuvenation of the Mobile Facial Zone.
Injectable hyaluronic acid-based fillers are commonly used for the correction of skin contour irregularities and to smooth skin depressions formed by volume loss during the aging process. These fillers are particularly efficient to restore perioral skin depressions/wrinkles or to correct topographical anomalies. The European directives require a continuous evaluation of the performance of these medical devices, particularly for CE marked products. An 18-month prospective randomized single-blind study for the efficacy and safety of ART FILLER Universal (AFU) was performed on the lips, the nasolabial folds, and the marionettes lines. The evaluations were performed on 153 subjects enrolled in this study. The efficacy, the longevity, and the safety were evaluated for the injected areas via area specific clinical scoring after a single injection with the filler and with no re-touch. We showed here that filler injection induced potent improvements of volume restoration after a single injection on all the treated areas. These beneficial properties of the filler were significant 3 weeks after injection and during the whole study period. Moreover, injections of the filler were well tolerated by the subjects. The recorded adverse events are routinely seen with HA fillers for face volume corrections, and most of these local reactions resolved within 14 days. AFU was well tolerated and showed a continuous efficacy for at least 18 months, in exploratory analyses.


Spinal plasticity in stroke patients after botulinum neurotoxin A injection in ankle plantar flexors.
The effect of botulinum neurotoxin A (BoNT-A) in stroke patients' upper limbs has been attributed to its peripheral action only. However, BoNT-A depressed recurrent inhibition of lumbar motoneurons, likely due to its retrograde transportation along motor axons affecting synapses to Renshaw cells. Because Renshaw cells control group Ia interneurons mediating reciprocal inhibition between antagonists, we tested whether this inhibition, particularly affected after stroke, could recover after BoNT-A. The effect of posterior tibial nerve (PTN) stimulation on tibialis anterior (TA) electromyogram (EMG) was investigated in 13 stroke patients during treadmill walking before and 1 month after BoNT-A injection in ankle plantar flexors. Before BoNT-A, PTN stimuli enhanced TA EMG all during the swing phase. After BoNT-A, the PTN-induced reciprocal facilitation in TA motoneurons was depressed at the beginning of swing and reversed into inhibition in midswing, but at the end of swing, the reciprocal facilitation was enhanced. This suggests that BoNT-A induced spinal plasticity leading to the recovery of reciprocal inhibition likely due to the withdrawal of inhibitory control from Renshaw cells directly blocked by the toxin. At the end of swing, the enhanced reciprocal facilitation might be due to BoNT-induced modification of peripheral afferent inputs. Therefore, both central and peripheral actions of BoNT-A can modify muscle synergies during walking: (1) limiting ankle muscle co-contraction in the transition phase from stance to swing, to assist dorsiflexion, and (2) favoring it from swing to stance, which blocks the ankle joint and thus assists the balance during the single support phase on the paretic limb.


Mortality and cause-of-death reporting and analysis systems in seven Pacific Island countries.
Mortality statistics are essential for population health assessment. Despite limitations in data availability, Pacific Island Countries are considered to be in epidemiological transition, with non-communicable diseases increasingly contributing to premature adult mortality. To address rapidly changing health profiles, countries would require mortality statistics from routine death registration given their relatively small population sizes. This paper uses a standard analytical framework to examine death registration systems in Fiji, Kiribati, Nauru, Palau, Solomon Islands, Tonga and Vanuatu. In all countries, legislation on death registration exists but does not necessarily reflect current practices. Health departments carry the bulk of responsibility for civil registration functions. Medical cause-of-death certificates are completed for at least hospital deaths in all countries. Overall, significantly more information is available than perceived or used. Use is primarily limited by poor understanding, lack of coordination, limited analytical skills, and insufficient technical resources. Across the region, both registration and statistics systems need strengthening to improve the availability, completeness, and quality of data. Close interaction between health staff and local communities provides a good foundation for further improvements in death reporting. System strengthening activities must include a focus on clear assignment of responsibility, provision of appropriate authority to perform assigned tasks, and fostering ownership of processes and data to ensure sustained improvements. These human elements need to be embedded in a culture of data sharing and use. Lessons from this multi-country exercise would be applicable in other regions afflicted with similar issues of availability and quality of vital statistics.


[Comparative study of the ultrastructure of vibrioid green sulfur bacteria].
The fine structure of the cells was investigated on the ultrathin sections of green sulphur bacteria, two strains of Chlorobium vibrioforme, two strains of Pelodictyon luteolum, and one strain of Pelodictyon phaeum. All strains possess similar photosynthetic structures --"chlorobium-vesicules" underlying the cytoplasmic membrane. Irregularly localized, gaseous vesicules of the rhombic shape were discerned in the cytoplasm of P. luteolum and P. phaeum. The vesicules were surrounded by a unilayer membrane. The cytoplasmic membrane produced invaginations of the mesosomal type. Elementary sulphur as a product of oxidation of hydrogen sulphide, is presumed to be liberated from the cells by means of sacs, or invaginations, formed by the cytoplasmic membrane. The taxonomy of the vibrioid green sulphur bacteria is discussed.


Determination of 4-hexylresorcinol in crab meat.
A method is described for determining 4-hexylresorcinol in crab meat. 4-Hexylresorcinol is used to prevent melanosis in shrimp, and the same use has been proposed for crab meat. Because 4-hexylresorcinol may be added illegally to crab meat as a preservative, consumer protection requires that residues of the compound be monitored in crab meat. 4-Hexylresorcinol is extracted from crab meat with acetonitrile. After dilution with water, the extract is passed through a C18 solid-phase extraction column and 4-hexylresorcinol is eluted from the column with ethanol. The compound is determined by reversed-phase liquid chromatography with diode array detection at 206 nm. Limit of quantitation is 1.0 microgram/g. Mean recovery in the range 1-20 micrograms/g is 89%, with a relative standard deviation of 6.3.


Extended DLVO calculations expose the role of the structural nature of the adsorbent beads during chromatography.
Protein adsorption onto hydrophobic interaction chromatography supports was studied by a surface-thermodynamics approach. To gather relevant experimental information, contact angle measurements and zeta potential determinations were performed on three different commercial adsorbent beads, Phenyl Sepharose 6 Fast Flow, Toyopearl Phenyl 650-C and Source 15 Phenyl, having soft to rigid backbone structure. Similar information was obtained for a collection of model proteins, lysozyme, bovine serum albumin (BSA), polygalacturonase, aminopeptidase, chymosin, aspartic protease, beta-galactosidase, human immunoglobulin G, and lactoferrin, were evaluated in the hydrated and in the dehydrated state. Based on the mentioned experimental data, calculations were performed to obtain the (interfacial) energy versus distance profiles of nine individual (model) proteins on (commercial) beads of three different types. All of these beads harbored the phenyl-ligand onto a matrix of differentiated chemical nature. Extended Derjaguin, Landau, Verwey, and Overbeek (DLVO) calculations were correlated with actual chromatographic behavior. Typical chromatography conditions were employed. The population of model proteins utilized in this study could be segregated into two groups, according to the minimum values observed for the resulting interaction energy pockets and the corresponding retention volumes (or times) during chromatography. Moreover, trends were also identified as a function of the type of adsorbent bead under consideration. This has revealed the influence of the physicochemical nature of the bead structure on the adsorption process and consequently, on the expected separation behavior.


(3h)J((15)N-(31)P) spin-spin coupling constants across N[bond]H....O[bond]P hydrogen bonds.
Equation-of-motion coupled cluster singles and doubles (EOM-CCSD) calculations have been performed to evaluate three-bond (15)N-(31)P coupling constants ((3h)J(N[bond]P)) across N[bond]H....O[bond]P hydrogen bonds in model cationic and anionic complexes including NH(4)(+):OPH, NH(4)(+):OPH(3), NH(3):(-)O(2)PH(2), NFH(2):(-)O(2)PH(2), and NF(2)H:(-)O(2)PH(2). Three-bond coupling constants can be appreciable when the phosphorus is P(V), but are negligible with P(III). (3h)J(N[bond]P) values in complexes with cyclic or open structures are less than 1 Hz, a consequence of the nonlinear arrangement of N, H, O, and P atoms. For complexes with these structures, (3h)J(N[bond]P) may not be experimentally measurable. In contrast, complexes in which the N, H, O, and P atoms are collinear or nearly collinear have larger values of (3h)J(N[bond]P), even though the N[bond]P distances are longer than N[bond]P distances in cyclic and open structures. In linear complexes, (3h)J(N[bond]P) is dominated by the Fermi-contact term, which is distance dependent. Therefore, N[bond]P (and hydrogen-bonding N[bond]O) distances in these complexes can be determined from experimentally measured (15)N-(31)P coupling constants.


Influence of age at diagnosis on the clinical characteristics of Crohn's disease in Korea: Results from the CONNECT study.
The present study evaluated the clinical characteristics of Korean patients with Crohn's disease (CD) according to their age at diagnosis in a nationwide multicenter cohort study. A total of 1224 patients diagnosed with CD between 1982 and 2008 in 32 hospitals were included, and age at diagnosis was categorized as ≤ 16 (G1), 17-40 (G2), 41-59 (G3) and ≥ 60 (G4) years old. The baseline characteristics, medication, and intestinal resection were compared according to the age at diagnosis. The number of patients in each age group was 155 (G1; 12.7%), 919 (G2; 75.1%), 120 (G3; 9.8%), and 30 (G4; 2.5%). The frequencies of ileocolonic disease in the late adult onset and elderly onset groups were lower than those in the other groups (P < 0.001). The cumulative probabilities of thiopurine and anti-tumor necrosis factor use in late adult onset and elderly onset groups were significantly reduced compared with those of the other groups (P < 0.01). However, the risk of the first intestinal resection was not different among the age groups. The ileal location (hazard ratio [HR]: 1.59; 95% confidence interval [CI]: 1.11-2.27), complicated behavior (HR: 3.35; 95% CI: 2.63-4.27), and early thiopurine use (HR: 0.27; 95% CI: 0.17-0.43) were associated with the first intestinal resection, whereas the age at diagnosis was not a risk factor. Elderly onset CD may be related to favorable outcomes in Korea. Thus, the heterogeneity of this disease should be considered when developing a tailored strategy for the treatment of CD.


GIS-based slope-adjusted curve number methods for runoff estimation.
Accurate estimation of surface runoff and determination of susceptible lands to runoff generation in ungauged watersheds were the problems for hydrologic engineering which could be predicted through a simple model such as Soil Conservation Service Curve Number (SCS-CN). Due to the slope effects on this method, slope adjustment for curve number was developed to improve its precision. So, the main objectives of this study were to apply GIS-based slope SCS-CN approaches for surface runoff estimation and compare the accuracy of three slope-adjusted models including: (a) model with three empirical parameters, (b) model with two parameters slope function, and (c) model with one parameter in the region located in the central part of Iran. For this purpose, soil texture, hydrologic soil group, land use, slope, and daily rainfall volume maps were utilized. In order to provide the curve number map of the study area, land use and hydrologic soil group layers built in Arc-GIS were intersected and the curve number was determined. Then, three slope adjustment equations were used to modify curve numbers of AMC-II by employing slope map. Finally, recorded runoff data of the hydrometric station were applied to assess the performance of the models through four statistical indicators of the root mean square error (RMSE), the Nash-Sutcliffe efficiency (E), the coefficient of determination [Formula: see text], and percent bias (PB). Land use map analysis showed that rangeland was the dominant land use, whereas the soil texture map specified the greatest and smallest area belonging to loam and sandy loam textures, respectively. Although the runoff results showed the overestimation of large rainfall values and underestimation for rainfall with less than 40 mm volume in both models, the values of E (0.78), RMSE (2), PB (16), and [Formula: see text] (0.88) revealed that eq. (a) with three empirical parameters was the most accurate equation. The maximum percent of runoff generated by rainfall for eqs. (a), (b), and (c) were 68.43, 67.28, and 51.57% which showed that bareland located in south part with the slope of more than 5% was susceptible to runoff generation and should be paid attention to watershed management.


The collagen microstructural changes of rat menisci and tibiofemoral cartilages under the influence of mechanical loading: An in vitro wear test of whole joints.
Knee osteoarthritis (OA) is suggested to be induced by multi-factors, and mechanical environment is regarded as a risky factor. To investigate the effect of isolated mechanical factor on cartilage. An active wear test system was designed to perform parameters-controlled in vitro wear tests on rat knee joints with specific load magnitude, flexion-extension angle, and movement frequency. Six hind limbs of 9-month-old male Sprague-Dawley rats, with an additional spring on the medial side, were worn by using the custom-designed apparatus. Researchers observed both the menisci and tibial cartilages of these hind limbs using multiphoton laser scanning microscopy to analyze the change of the collagen microstructure caused by wear. Collagen microstructure of both the medial and lateral meniscus became disordered under cyclic load. Some tissues on the surface of the medial tibial cartilage were removed and the middle layer of the medial compartment displayed cracks. On the contrary, the lateral tibial cartilage was intact. The results implied that cyclic load caused menisci microstructure disarrangement prior to tibial cartilage damage and the collagen structure of mid-layer tibial cartilage failed before that of the superficial layer under the kinematics adopted in the study.


Agile Detection of Chemical Warfare Agents by Machine Vision: a Supramolecular Approach.
The supramolecular detection by image analysis of a simulant chemical warfare agent on a solid device containing a selective molecular sensor based on a BODIPY scaffold is reported. The recognition properties were investigated in solution, demonstrating high affinity (log K 6.60) and sensitivity (LOD 10 ppt). A test strip also confirmed the sensing properties in gas phase. Image analysis of the solid device allows quantitative information about the simulant to be obtained, recovering the sensor almost 5 times and thus confirming the goal of the supramolecular approach.


Screening for occult faecal blood loss in a community by means of Hemoccult II slides and a tetramethylbenzidine test.
A total of 754 persons statistically selected from the age group 54-64 years were asked by letter to provide faecal samples for screening of occult blood during dietary restrictions. A total of 413 persons (55%) returned an average of 5.8 (range, 1-6) faecal samples each. All the faecal specimens were analysed with Hemoccult II slides and the 3,3',5,5'-tetramethylbenzidine (TMB) test 0.10%. For technical reasons, however, the Hemoccult test could not be evaluated. The TMB test showed faecal blood in 50 persons. A case history was obtained in 49 persons, of whom 47 agreed to further clinical, radiological, and endoscopic investigations. The most important findings in these examinations were resectable colonic carcinoma (Dukes's stage B) in 1 subject, a gastric ulcer in 1, haemorrhagic gastritis in 1, duodenal ulcers in 2, and colorectal polyps in 11 persons. The cost of the study was estimated to be NOK 114,000 (about USD 16,000).


Guideline-recommended medications: variation across Medicare Advantage plans and associated mortality.
To evaluate variation in the prescription of guideline-recommended medications across Medicare Advantage (MA) plans and to determine whether such variation is associated with increased mortality. Observational study of 111,667 patients aged 65 years or older receiving care in 203 MA plans. We linked data from the Medicare Health Outcomes (HOS) Survey cohort 9 (April 2006-May 2008) with the Medicare Part D prescription benefit files (January 1, 2006-December 31, 2007) to examine variation in treatment across MA plans and its association with differences in observed (O)/expected (E) mortality ratio for 5 high-volume chronic conditions: diabetes, coronary artery disease (CAD), congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD)/asthma, and depression. Analysis of variance confirmed that the 203 MA plans differed significantly in their use of guideline-recommended treatment (P≤0.02). Those MA plans with higher use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (r=-0.40; P<0.0001) and beta-blockers (r=-0.27; P<0.0001) in patients with CHF were significantly associated with lower O/E mortality ratios. Those MA plans with higher use of multiple guideline-recommended medications were significantly associated with lower O/E mortality ratios in CHF (r=-0.45; P<0.0001) and diabetes (r=-0.14; P<0.042). There were no significant associations between the variation in performance indicators and mortality ratios in patients with CAD and COPD/asthma. Those MA plans with higher use of antidepressant medications had significantly higher O/E mortality ratios (r=0.28, P<0.0001). There was wide variation across MA plans in the prescription of guideline-recommended medications that had a measurable relationship to the mortality of elderly patients with CHF and diabetes. These findings can serve to both motivate and target quality improvement programs.


Photocatalytic Degradation Enhancement in Pickering Emulsions Stabilized by Solid Particles of Bare TiO2.
Pickering emulsions provide a new way to enhance the efficiency of photocatalytic degradation of water-insoluble pollutants. Indeed, the semiconductor solid particles dually act as the photocatalyst and stabilizer of the emulsion droplets whose size dramatically affects the photocatalytic reaction. The present work aims at the validation of this concept by using bare TiO2 without any surface modification. Nanostructured TiO2 has been prepared by a simple sol-gel process and characterized by X-ray diffraction, specific surface area analysis, scanning electron microscopy, and diffuse reflectance spectroscopy. The emulsions were prepared by using 1-methylnaphthalene (1-MN) as a model organic contaminant scarcely soluble in water and bare TiO2 as the photocatalyst/stabilizer. The emulsions have been characterized by electrical conductivity, optical microscopy, and light-scattering analyses. The photocatalytic degradation of 1-MN was 50 times faster in stable Pickering emulsions with respect to the case of biphasic liquid systems containing TiO2. This finding allows us to propose Pickering emulsions stabilized by TiO2 nanoparticles as an effective and novel way to intensify the photocatalytic degradation of water-insoluble organic pollutants.


Therapeutic use of recombinant human G-CSF (rhG-CSF) in a canine model of sublethal and lethal whole-body irradiation.
The short biologic half-life of the peripheral neutrophil (PMN) requires an active granulopoietic response to replenish functional PMNs and to maintain a competent host defence in irradiated animals. Recombinant human G-CSF (rhG-CSF) was studied for its ability to modulate haemopoiesis in normal dogs as well as to decrease therapeutically the severity and duration of neutropenia in sublethally and lethally irradiated dogs. For the normal dog, subcutaneous administration of rhG-CSF induced neutrophilia within hours after the first injection; total PMNs continued to increase (with plateau phases) to mean peak values of 1000 per cent of baseline at the end of the treatment period (12-14 days). Bone-marrow-derived granulocyte-macrophage colony-forming cells (GM-CFC) increased significantly during treatment. For a sublethal 200 cGy dose, treatment with rhG-CSF for 14 consecutive days decreased the severity and shortened the duration of neutropenia and thrombocytopenia. The radiation-induced lethality of 60 per cent after a dose of 350 cGy was associated with marrow-derived GM-CFC survival of 1 per cent. Treatment with rhG-CSF markedly reduced the lethality associated with exposure to 350 cGy of radiation to zero. White blood cell (WBC) and platelet recovery kinetics were correlated with degree of marrow damage. The rhG-CSF reduced the severity and duration of neutropenia. Control animals required antibiotic therapy (WBC less than 1000 mm3) for a total of 16 days versus 3 days for rhG-CSF-treated dogs. The duration of thrombocytopenia was reduced, although the severity of depletion was unchanged with treatment. These data indicate that in the lethally irradiated dog, effective cytokine therapy with rhG-CSF will increase survival through the induction of earlier recovery of neutrophils and platelets.


Kidney disease and multiple myeloma.
Kidney injury is a common complication of multiple myeloma and other plasma cell dyscrasias, and it is associated with increased mortality. Multiple pathogenic mechanisms can contribute to kidney injury in the patient with myeloma, some of which are the result of nephrotoxic monoclonal Ig and some of which are independent of paraprotein deposition. The pathogenic mechanisms that underlie paraprotein-related kidney disease are increasingly well understood. A novel assay allowing the quantification of free light chains in the serum has aided the diagnosis of new onset disease and allowed for the earlier detection of relapse. Novel myeloma agents have shown considerable promise in reversing renal failure in some patients and improving outcomes. Stem cell transplantation remains a mainstay of management for younger patients with myeloma who are suitable candidates for intensive therapy, whereas the role of new drugs, plasma exchange, and kidney transplantation continues to evolve.


Excitonic Properties of Ordered Metal Nanocluster Arrays: 2D Silver Clusters at Multiporphyrin Templates.
The design of ordered arrays of metal nanoclusters such as, for example, two-dimensional cluster-organic frameworks might open a new route toward the development of materials with tailored optical properties. Such systems could serve as plasmonically enhanced light-harvesting materials, sensors, or catalysts. We present here a theoretical approach for the simulation of the optical properties of ordered arrays of metal clusters that is based on the ab initio parametrized Frenkel exciton model. We demonstrate that small atomically precise silver clusters can be assembled in one- and two-dimensional arrays on suitably designed porphyrin templates exhibiting remarkable optical properties. By employing explicit time-dependent density functional theory calculations on smaller homologues, we show that the intrinsic optical properties of metal clusters are largely preserved but undergo J- and H-type excitonic coupling that results in controllable splitting of their excited states. Furthermore, ab initio parametrized Frenkel exciton model calculations allow us to predict an energetic splitting of up to 0.77 eV in extended two-dimensional square arrays and 0.79 eV in tilted square aggregates containing up to 25 cluster-porphyrin subunits.


Principles of Charge Estimation Methods Using High-Frequency Current Transformer Sensors in Partial Discharge Measurements.
This paper describes a simplified model and a generic model of high-frequency current transformer (HFCT) sensors. By analyzing the models, a universal charge estimation method based on the double time integral of the measured voltage is inferred. The method is demonstrated to be valid irrespective of HFCT sensor, assuming that its transfer function can be modelled as a combination of real zeros and poles. This paper describes the mathematical foundation of the method and its particularities when applied to measure nanosecond current pulses. In practice, the applicability of the method is subjected to the characteristics and frequency response of the sensor and the current pulse duration. Therefore, a proposal to use the double time integral or the simple time integral of the measured voltage is described depending upon the sensor response. The procedures used to obtain the respective calibration constants based on the frequency response of the HFCT sensors are explained. Two examples, one using a HFCT sensor with a broadband flat frequency response and another using a HFCT sensor with a non-flat frequency response, are presented.


MicroRNA‑130a inhibits growth and metastasis of osteosarcoma cells by directly targeting ZEB1.
Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. microRNAs (miRNAs) have previously been reported to be involved in the carcinogenesis and progression of OS, and may be useful prognostic markers or therapeutic targets for patients with OS. miRNA‑130a has been previously studied in multiple types of human cancer. However, its expression and function in OS has not been well documented. The aim of the present study was to investigate the expression, biological functions and molecular mechanisms underlying the effect of miR‑130a in OS. miR‑130a was significantly downregulated in OS tissues and cell lines compared with normal bone tissue and a normal osteoblast cell line. miR‑130a expression levels was significantly negatively correlated with the clinical stage and metastasis of OS. Further studies indicated that overexpression of miR‑130a inhibited OS cell proliferation, migration and invasion in vivo. In terms of the mechanisms underlying this effect, zinc finger E‑box binding homeobox 1 (ZEB1) was demonstrated to act as a direct target of miR‑130a in OS. Furthermore, downregulation of ZEB1 by interference with small interfering RNA mimicked the effects of transfection with an miR‑130a mimic in OS. In conclusion, these results demonstrated that miR‑130a functioned as a tumor suppressor in OS, partially via targeting ZEB1, suggesting that miR‑130a may be considered as a target for the treatment of patients with OS.


Neuroparalytic keratopathy as the first sign of a cerebral meningioma.
We report a case of a cavernous sinus meningioma in a young woman presenting with a neuroparalytic corneal ulcer as the only sign of the tumour. Clinical ophthalmic examination revealed a trophic corneal ulcer in the left eye of the patient accompanied by corneal anaesthesia and loss of sensation to touch and pain stimuli in the ipsilateral dermatomes supplied by the ophthalmic and maxillary divisions of the trigeminal nerve. A MRI scan of the head revealed a left cavernous sinus meningioma. Neuroparalytic keratopathy or corneal ulcer is an infrequent presenting sign of intracranial pathology. The diagnosis can be missed if the neuroparalytic nature of corneal condition is not detected by the ophthalmologist.


Correlation between SNPs in CDH1 and gastric cancer in Chinese population.
Many recent studies revealed that the single nucleotide polymorphisms have considerable effects on the susceptibility of cancer, such as prostate cancer, lung cancer and gastric cancer. The E-cadherin, a calcium-dependent transmembrane glycoprotein encoded by CDH1 gene, is critical for epithelial construction, intercellular adhesion and cell migration. Some associations have been reported between single nucleotide polymorphisms and gastric cancer in the Chinese population. To investigate whether the single nucleotide polymorphism in CDH1 gene is associated with the susceptibility of gastric cancer in the Chinese population. The genotypes of 5 known single nucleotide polymorphisms (rs33935154, rs121964871, rs121964874, rs121964875, rs121964876) were determined in 359 gastric cancer patients and 368 healthy controls. High resolution melting curve detection and sequencing analysis were used in the present study. There is a statistical significance in the rs121964871 C>G polymorphism between gastric cancer patients and healthy controls (OR=1.769, 95%CI: 1.051-2.976). Elderly male individuals (>50 years of age) carrying this risk factor may be more susceptible to gastric cancer. The results indicated that the rs121964871 C>G polymorphism is associated with the susceptibility of gastric cancer in the Chinese population, with some age and sex-dependent tendencies observed.


The EGFR variant III mutant as a target for immunotherapy of glioblastoma multiforme.
In epithelial tumors, the epidermal growth factor receptor (EGFR) controls key signaling pathways responsible for growth, proliferation, migration, and survival of tumor cells. The epidermal growth factor receptor variant III (EGFRvIII) is the most common EGFR mutation that occurs in up to 30% of high-grade gliomas especially glioblastoma multiforme (GBM). EGFRvIII arises from the deletion of exon 2-7 that leads to the formation of the constitutively activated mutant receptor incapable of binding any known ligand. EGFRvIII-expressing cells are resistant to EGFR inhibitors and therefore take advantage in survival. Furthermore, EGFRvIII expression in tumors is often correlates with poor prognosis. Indeed, EGFRvIII targeting is of great therapeutic value in order to inhibit GBM progression and invasion. The presence of the unique glycine site in EGFRvIII provides an option to develop EGFRvIII-specific monoclonal antibodies (MAbs). These antibodies are used for detection of EGFRvIII and immunotherapy. Peptide CDX-110 derived from EGFRvIII has high immunogenicity. This peptide was used for the development of anti-EGFRvIII MAbs with improved specificity to the mutant receptor, EGFRvIII-specific dendritic cell vaccine, and CDX-110-KLH peptide vaccine. These immune reagents were successfully tested in preclinical and clinical studies for GBM treatment.


Addiction recovery: its definition and conceptual boundaries.
The addiction field's failure to achieve consensus on a definition of "recovery" from severe and persistent alcohol and other drug problems undermines clinical research, compromises clinical practice, and muddles the field's communications to service constituents, allied service professionals, the public, and policymakers. This essay discusses 10 questions critical to the achievement of such a definition and offers a working definition of recovery that attempts to meet the criteria of precision, inclusiveness, exclusiveness, measurability, acceptability, and simplicity. The key questions explore who has professional and cultural authority to define recovery, the defining ingredients of recovery, the boundaries (scope and depth) of recovery, and temporal benchmarks of recovery (when recovery begins and ends). The process of defining recovery touches on some of the most controversial issues within the addictions field.


[The need for a postgraduate training curriculum in anatomic pathology/clinical pathology in Japan--a personal experience].
After I graduated from Nagoya University School of Medicine in 1979, I was trained as a resident and physician at Nagoya Ekisaikai Hospital for 4 years. Then, I was trained as an anatomic pathologist by individual discussions of diagnostic problems using a multi-headed microscope at the Division of Pathology, Clinical Laboratory, Nagoya University Hospital for 5 years. When I entered the field of clinical pathology, there were few experienced clinical pathologists in Nagoya, so I needed the support of medical technologists for training in this field. Recently, I have been advancing my career as a clinical pathologist by offering consultations to physicians and holding a reversed clinico-pathological conference for medical technologists. It took me about 20 years to become a fully qualified pathologist. I think that a systematic curriculum for postgraduate training in anatomic pathology/clinical pathology should be indispensable to pathologists.


ANGPT1 methylation and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage patients.
Delayed cerebral ischemia (DCI) is a common secondary complication and an important cause of disability and mortality among patients who survive aneurysmal subarachnoid hemorrhage (aSAH). Knowledge on DCI pathogenesis, risk factors, and biomarkers are essential for early detection and improved prognosis. To investigate the role of DNA methylation in DCI risk, we conducted an epigenome-wide association study (EWAS) in 68 patients followed up to 1 year after the initial aneurysm rupture. Blood samples were collected within 48 h post hemorrhage and used for DNA methylation profiling at ~ 450k CpG sites. A separate cohort of 175 patients was sequenced for the top CpG sites from the discovery analysis for a replication of the EWAS findings. EWAS did not identify any epigenome-wide significant CpGs. The top signal, cg18031596, was annotated to ANGPT1, a gene with critical functions in angiogenesis after vascular injury. Post hoc power calculations indicated a well-powered discovery analysis for cg18031596. Analysis of the replication cohort showed that four out of the five CpG sites sequenced at the ANGPT1 locus passed a Bonferroni-adjusted significance threshold. In a pooled analysis of the entire sample, three out of five yielded a significant p-value, and the top association signal (p-value = 0.004) was seen for a CpG that was not originally measured in the discovery EWAS. However, four ANGPT1 CpG sites had an opposite effect direction in the replication analysis compared to the discovery EWAS, marking a failure of replication. We carefully examined this observed flip in directions and propose several possible explanations in addition to that it was a random chance that ANGPT1 ranked at the top in the discovery EWAS. We failed to demonstrate a significant and consistent effect of ANGPT1 methylation in DCI risk in two cohorts. Though the replication attempt to weaken the overall support of this gene, given its relevant function and top rank of significance in the EWAS, our results call for future studies of larger aSAH cohorts to determine its relevance for the occurrence of DCI.


Mendelian Inheritance of Paralytic Shellfish Poisoning Toxin in the Marine Dinoflagellate Alexandrium catenella.
To analyze the genetic system of paralytic shellfish poisoning (PSP) toxin production in the dinoflagellate Alexandrium catenella, we examined toxin compositions and mating type of Fl progenies from crosses between algal strains having different toxin compositions. In all strains used, the mole percentage of their toxin composition did not significantly change in any growth phase, although total toxin levels increased rapidly in the early to middle exponential growth phase and then decreased by 95% in the stationary phase. One parental strain produced gonyautoxin (GTX) 4, and C4, while the other produced neosaxitoxin (neoSTX) and saxitoxin (STX) during all growth phases. Fl progenies showed one parental toxin composition and segregated independently with the mating type. These data suggest that A. catenella is a toxin producer and that Mendelian inheritance of toxin profiles occurs in the heterothallic dinoflagellate A. catenella.


Description of the photoperiodic control of larval burrowing in the blowfly Lucilia cuprina: a novel index for photoperiodic research.
The photoperiodic control of larval burrowing depth in the Australian sheep blowfly Lucilia cuprina (Wiedemann) (Diptera: Calliphoridae) was investigated by measuring burrowing depth under controlled laboratory photoperiods. The results demonstrated that larvae exposed to long photoperiods (LD 18 : 6) burrowed to deeper depths than those in shorter photoperiods (LD 12 : 12), and that this behavior was induced during the third instar stage. The ecological significance of this behavior is discussed, as are the ways in which daylength is measured and depth assessed. The use of burrowing depth could prove to be a novel index of a photoperiodic response and provide a far simpler approach to the study of photoperiodism in certain insect species.


Towards best practice of interpreting deep learning models for EEG-based brain computer interfaces.
As deep learning has achieved state-of-the-art performance for many tasks of EEG-based BCI, many efforts have been made in recent years trying to understand what have been learned by the models. This is commonly done by generating a heatmap indicating to which extent each pixel of the input contributes to the final classification for a trained model. Despite the wide use, it is not yet understood to which extent the obtained interpretation results can be trusted and how accurate they can reflect the model decisions. We conduct studies to quantitatively evaluate seven different deep interpretation techniques across different models and datasets for EEG-based BCI. The results reveal the importance of selecting a proper interpretation technique as the initial step. In addition, we also find that the quality of the interpretation results is inconsistent for individual samples despite when a method with an overall good performance is used. Many factors, including model structure and dataset types, could potentially affect the quality of the interpretation results. Based on the observations, we propose a set of procedures that allow the interpretation results to be presented in an understandable and trusted way. We illustrate the usefulness of our method for EEG-based BCI with instances selected from different scenarios.


Sleep Disorder as a Triggering Factor for Relapse in Multiple Sclerosis.
To determine the effect of sleep disturbances on predisposing multiple sclerosis (MS) patients for acute relapse. This case-control study was conducted on 80 MS patients including 40 patients in the remission phase and 40 in the relapse phase. Patients were asked to fill in the Pittsburgh Sleep Quality Index to determine their sleep quality during the previous month. Individuals with scores of 5 or less were considered having normal sleep quality. Mean ± SD ages were 32.5 ± 7.7 and 30.2 ± 7.2 years among patients with and without acute relapses, respectively (p > 0.05). The mean disease duration and disease severity (according to Expanded Disability Status Scale [EDSS]) were comparable across the groups (p > 0.05). Among those with and without acute exacerbations, 87.5 and 50% had poor sleep quality, respectively (p = 0.0001), with OR of 1.75 (95% CI 1.25-2.43). The age, gender, EDSS, and disease duration did not associate with sleep quality in either groups (p > 0.05). This study showed that sleep disturbance might be a trigger for an acute MS exacerbation. Increasing the awareness of specialists and routine screening of sleep disorders in MS patients are warranted, as treatment of these disorders might decrease the likelihood of acute relapses.


Charting the acquisition of semantic knowledge in a case of developmental amnesia.
We report the acquisition and recall of novel facts by Jon, a young adult with early onset developmental amnesia whose episodic memory is gravely impaired due to selective bilateral hippocampal damage. Jon succeeded in learning some novel facts but compared with a control group his intertrial retention was impaired during acquisition and, except for the most frequently repeated facts, he was also less accurate in correctly sourcing these facts to the experiment. The results further support the hypothesis that despite a severely compromised episodic memory and hippocampal system, there is nevertheless the capacity to accrue semantic knowledge available to recall.


Medical emergency team response processes for behavioral health inpatient units: implications for nursing education.
Following a literature review of nurses' attitudes and perceived barriers regarding the utilization of medical emergency teams (METs) and completing key informant interviews with psychiatric nurses, a questionnaire developed by the researcher was administered to inpatient psychiatric nurses to further examine their attitudes and perceived barriers about MET utilization. Using a 23-item questionnaire, the psychiatric nurses were asked to rate each item using a 5-point Likert scale. Results indicated that nurses did not have a clear understanding of the criteria for calling a MET and also tended to seek out other staff personnel and/or a physician consultation prior to initiating a MET call. Results of this descriptive, quality improvement project were then used to revise and refine nursing education and practice regarding MET utilization.


The Interaction of Water with Free Mn4 O4 (+) Clusters: Deprotonation and Adsorption-Induced Structural Transformations.
As the biological activation and oxidation of water takes place at an inorganic cluster of the stoichiometry CaMn4 O5 , manganese oxide is one of the materials of choice in the quest for versatile, earth-abundant water splitting catalysts. To probe basic concepts and aid the design of artificial water-splitting molecular catalysts, a hierarchical modeling strategy was employed that explores clusters of increasing complexity, starting from the tetramanganese oxide cluster Mn4 O4 (+) as a molecular model system for catalyzed water activation. First-principles calculations in conjunction with IR spectroscopy provide fundamental insight into the interaction of water with Mn4 O4 (+) , one water molecule at a time. All of the investigated complexes Mn4 O4 (H2 O)n (+) (n=1-7) contain deprotonated water with a maximum of four dissociatively bound water molecules, and they exhibit structural fluxionality upon water adsorption, inducing dimensional and structural transformations of the cluster core.


Mitochondrial Dysfunction Was Involved in Decabromodiphenyl Ethane-Induced Glucolipid Metabolism Disorders and Neurotoxicity in Zebrafish Larvae.
Decabromodiphenyl ethane (DBDPE), a novel brominated flame retardant, is becoming increasingly prevalent in environmental and biota samples. While DBDPE has been shown to cause various biological adverse effects, the molecular mechanism behind these effects is still unclear. In this research, zebrafish embryos were exposed to DBDPE (50-400 μg/L) until 120 h post fertilization (hpf). The results confirmed the neurotoxicity by increased average swimming speed, interfered neurotransmitter contents, and transcription of neurodevelopment-related genes in zebrafish larvae. Metabolomics analysis revealed changes of metabolites primarily involved in glycolipid metabolism, oxidative phosphorylation, and oxidative stress, which were validated through the alterations of multiple biomarkers at various levels. We further evaluated the mitochondrial performance upon DBDPE exposure and found inhibited mitochondrial oxidative respiration accompanied by decreased mitochondrial respiratory chain complex activities, mitochondrial membrane potential, and ATP contents. However, addition of nicotinamide riboside could effectively restore DBDPE-induced mitochondrial impairments and resultant neurotoxicity, oxidative stress as well as glycolipid metabolism in zebrafish larvae. Taken together, our data suggest that mitochondrial dysfunction was involved in DBDPE-induced toxicity, providing novel insight into the toxic mechanisms of DBDPE as well as other emerging pollutants.


Pulmonary blood volume: correlation of equilibrium radionuclide and dye-dilution estimates.
In fifteen prospective patients with aortic stenosis undergoing transseptal cardiac catheterization, dye-dilution and count-based estimates of pulmonary blood volume (PBV) were performed. Three radionuclide methods were evaluated. Two were based on electrocardiogram (ECG)-gated imaging of the thorax, where pulmonary counts (PC) were corrected for frame-time, venous radioactivity, and either (1) the number of processed heart beats or (2) the total duration of acquisition. The third method involved ungated frame mode acquisitions, where PC were corrected for the duration of acquisition and the venous activity. PC (per channel element) were derived from manual assignments of the right lung. All methods correlated well with standard dye-dilution techniques (r greater than 0.82), though at greater volumes it was clear that count-based methods underestimated the dye-dilution values. In five acutely instrumented, anesthetized dogs, radionuclide (ungated formula) and dye-dilution estimates of PBV were made during multiple interventions (19 data points). The five control count volumes as well as the 14 separate intervention points correlated well (r greater than 0.89). It is concluded that PC from equilibrium blood pool images reflect PBV and that induced changes in PC can be utilized as a reflection of changes in PBV.


Attention and Working Memory in Female Adolescents With Chronic Pain and Pain-free Female Adolescents: A Preliminary Pilot Study.
Adolescents with chronic pain often report inattention and poor memory. There has been little research on cognitive function in this population. The goal of this preliminary pilot study was to examine differences in cognitive function between adolescents with chronic pain to pain-free adolescents. All participants completed baseline assessments of pain, school absences, depression, anxiety, and sleep habits. Standardized neurocognitive tests were used to examine cognitive function with a focus on working memory and attention. Recruitment from the chronic pain clinic resulted in a female sample of 13 individuals (largely reflective of the clinical population). Pain-free age-matched and sex-matched individuals (n=12) were therefore also recruited as controls. Individuals with chronic pain had significantly lower working memory scores than controls. Differences were found between groups on the most difficult selective attention task and not on tests of sustained attention, divided attention, or attentional switching. In a stepwise regression with baseline characteristics entered in the first step, pain accounted for approximately 15% of the variance in working memory and medication score counted for 49% of the variance. This pilot study is the first study to examine differences in working memory and attention between participants with chronic pain and pain-free adolescents. Our findings suggest that chronic pain may negatively affect adolescents' working memory function and highlights the risk for cognitive difficulties and problems with educational progression in addition to negative health and social effects associated with chronic pain. The study provides a starting point for more research and has the potential to direct better identification and treatment of these cognitive deficits.


Structural acoustics of good and bad violins.
Modal-acoustic radiation measurements on 17 "bad-to-excellent" quality-rated violins--including three-dimensional modal analyses of Titian and Willemotte Stradivari and Plowden Guarneri del Gesu violins to investigate extensional as well as flexural motions-were examined for quality-related trends, generally by contrasting the properties of "excellent" and "bad" violins. All violins tested showed the same five "signature" modes below 600 Hz, with no obvious quality trends for mode frequencies or total damping. Bad-excellent comparisons of band-/modal-averaged damping (total, radiation and internal), mobility, radiativity, directivity, fraction-of-vibrational-energy radiated, effective critical frequency, and radiativity profiles up to 4 kHz generally showed no significant difference; the only "robust" quality differentiator was the approximately 280 Hz, Helmholtz-type A0 cavity mode radiativity where excellent violins were significantly higher. Radiation and total damping of two old Italian violins appeared slightly higher than those for bad violins below 2 kHz, partly due to lower effective critical frequency and partly because of slightly lower mass. Stradivari violins showed the highest and lowest directivity of all instruments tested. The Titian and Plowden top plate flexural/extensional mobility ratios appeared correlated with their directivity. Extensional motion in the "bridge island" between f holes peaked near 2.4 kHz, coinciding with the BH peak and a bridge/bridge-island impedance ratio minimum.


Superoxide anion production in response to bacterial lipopolysaccharide and fungal spores implicated in organic dust toxic syndrome.
High amounts of fungal spores, bacteria, and bacterial endotoxin have been found in dust associated with the poorly characterized syndrome, organic dust toxic syndrome (ODTS). As part of an ongoing investigation to determine the etiopathogenesis for ODTS, this study has focused on activation of guinea pig bronchial alveolar lavage (BAL) cells as evidenced by the production of superoxide anion in response to fungal spores and lipopolysaccharide (LPS). Fungal spores from Aspergillus candidus, Aspergillus terreus, Aspergillus niger, Aspergillus fumigatus, Eurotima amstelodami, Penicillium spinulosum, and Cladosporium cladosporioides were all shown to increase superoxide anion production, each with different potencies. LPS stimulated little superoxide anion production in BAL cells, but when cells were pretreated with LPS prior to stimulation with fungal spores, superoxide anion production was increased over that induced by either spores or LPS alone. These results suggest that the inhalation of LPS together with fungal spores could possibly provoke abnormal lung pathologies.


Cost-Effectiveness of Acthar Gel versus Standard of Care for the Treatment of Advanced Symptomatic Sarcoidosis.
Sarcoidosis is a multisystem, inflammatory, systemic granulomatous disease with unknown etiology. Despite the current standard of care (SoC), there is an unmet need for the treatment of advanced symptomatic sarcoidosis. This study assessed the cost-effectiveness of Acthar® Gel (repository corticotropin injection) versus SoC in patients with advanced symptomatic sarcoidosis from the United States (US) payer and societal perspectives over 2 and 3 years. A probabilistic cohort-level state-transition approach was used for this cost-effectiveness analysis. Patients were monitored at the end of a 3-month cycle for the attainment of partial or complete response. Patients in the partial, complete, or no-response state were allowed to transition in each of these states at each 3-month cycle. Following the attainment of response, patients could have a durable response or relapse to a no-response state. Patients in a no-response state received treatment and could transition into a response or no-response state based on the probability of treatment success with the respective treatment. Clinical parameters and health utility data were sourced from the Acthar Gel in Participants with Pulmonary Sarcoidosis (PULSAR) trial (NCT03320070) and healthcare utilization, costs, and disutilities were sourced from the published literature. Base case analysis considered a payer perspective over 2 years. From a payer perspective, Acthar Gel versus SoC results in an incremental cost-effectiveness ratio (ICER) of $134,796 per quality-adjusted life-year (QALY) and $39,179 per QALY over 2 and 3 years, respectively. From a societal perspective, Acthar Gel versus SoC results in an ICER of $117,622 per QALY and $21,967 per QALY over 2 and 3 years, respectively. Sensitivity analysis findings were consistent with the base case. The results from this cost-effectiveness analysis indicate that Acthar Gel is a cost-effective, value-based treatment option for advanced symptomatic sarcoidosis compared to the SoC from the US payer and societal perspectives.


Synthetic methods, chemistry, and the anticonvulsant activity of thiadiazoles.
The chemistry of heterocyclic compounds has been an interesting field of study for a long time. Heterocyclic nucleus 1,3,4-thiadiazole constitutes an important class of compounds for new drug development. The synthesis of novel thiadiazole derivatives and investigation of their chemical and biological behavior have gained more importance in recent decades. The search for antiepileptic compounds with more selective activity and lower toxicity continues to be an active area of intensive investigation in medicinal chemistry. During the recent years, there has been intense investigation of different classes of thiadiazole compounds, many of which possess extensive pharmacological activities, namely, antimicrobial activity, anticonvulsant, antifungal antidiabetic, anti-inflammatory, antioxidant, and antituberculosis activities, and so forth. The resistance towards available drugs is rapidly becoming a major worldwide problem. The need to design new compounds to deal with this resistance has become one of the most important areas of research today. Thiadiazole is a versatile moiety that exhibits a wide variety of biological activities. Thiadiazole moiety acts as "hydrogen binding domain" and "two-electron donor system." It also acts as a constrained pharmacophore. On the basis of the reported literature, we study here thiadiazole compounds and their synthetic methods chemistry and anticonvulsant activity.


Effects of mazindol on lipid metabolism of human adipose tissue in vitro.
The interaction of mazindol with catecholamine in regulating peripheral lipid metabolism was studied in vitro. Noradrenaline-induced and adrenaline-induced glycerol release was augmented by addition of 50 ng mazindol. On the other hand, isoproterenol-induced glycerol release was suppressed by addition of 50 ng mazindol. Basal and dopamine-induced glycerol release was not altered by addition of 50 ng mazindol. These results suggest that mazindol may interact with alpha 2-adrenergic receptors in adipose tissue.


The Cerebellar Dopaminergic System.
In the central nervous system (CNS), dopamine (DA) is involved in motor and cognitive functions. Although the cerebellum is not been considered an elective dopaminergic region, studies attributed to it a critical role in dopamine deficit-related neurological and psychiatric disorders [e.g., Parkinson's disease (PD) and schizophrenia (SCZ)]. Data on the cerebellar dopaminergic neuronal system are still lacking. Nevertheless, biochemical studies detected in the mammalians cerebellum high dopamine levels, while chemical neuroanatomy studies revealed the presence of midbrain dopaminergic afferents to the cerebellum as well as wide distribution of the dopaminergic receptor subtypes (DRD1-DRD5). The present review summarizes the data on the cerebellar dopaminergic system including its involvement in associative and projective circuits. Furthermore, this study also briefly discusses the role of the cerebellar dopaminergic system in some neurologic and psychiatric disorders and suggests its potential involvement as a target in pharmacologic and non-pharmacologic treatments.


Expression of Toll-like receptors 3, 7, 9 and cytokines in feline infectious peritonitis virus-infected CRFK cells and feline peripheral monocytes.
The role of Toll-like receptors (TLRs) in a feline infectious peritonitis virus (FIPV) infection is not completely understood. This study examined the expression of TLR3, TLR7, TLR9, tumor necrosis factor-alpha (TNF-α), interferon (IFN)-β, and interleukin (IL)-10 upon an FIPV infection in Crandell-Reese feline kidney (CRFK) cells and feline monocytes. CRFK cells and monocytes from feline coronavirus (FCoV)-seronegative cats and FCoV-seropositive cats were infected with type II FIPV-79-1146. At four, 12, and 24 hours post-infection (hpi), the expression of TLR3, TLR7, TLR9, TNF-α, IFN-β, and IL-10, and the viral load were measured using reverse transcription quantitative polymerase chain reaction. Viral protein production was confirmed using immunofluorescence. FIPV-infected CRFK showed the upregulation of TLR9, TNF-α, and IFN-β expression between 4 and 24 hpi. Uninfected monocytes from FCoV-seropositive cats showed lower TLR3 and TLR9 expression but higher TLR7 expression compared to uninfected monocytes from FCoV-seronegative cats. FIPV-infected monocytes from FCoV-seropositive cats downregulated TLR7 and TNF-α expression between 4 and 24 hpi, and 4 and 12 hpi, respectively. IFN-β was upregulated early in FIPV-infected monocytes from FCoV-seropositive cats, with a significant difference observed at 12 hpi compared to FCoV-seronegative cats. The viral load in the CRFK and FIPV-infected monocytes in both cohorts of cats was similar over time. TLR7 may be the key TLR involved in evading the innate response against inhibiting TNF-α production. Distinct TLR expression profiles between FCoV-seronegative and FCoV-seropositive cats were observed. The associated TLR that plays a role in the induction of IFN-β needs to be explored further.


The effect of injection speed on remifentanil-induced cough in children.
Remifentanil sometimes elicits cough during induction of anesthesia, as with the use of other fentanyl congeners. We designed this study to investigate the incidence of remifentanil-induced cough (RIC) in children and to evaluate the effect of injection speed on RIC. One hundred twenty ASA physical status I-II patients, aged 3-12 yr, undergoing general anesthesia were enrolled in the study. Patients were randomly assigned to one of the three groups. Patients in Group R30 received remifentanil 1.5 µg/kg at a constant rate over 30 s. Patients in Group R45 received remifentanil 1.5 µg/kg over 45 s, and patients in Group R60 received remifentanil 1.5 µg/kg over 60 s, respectively. Episodes of cough were recorded and graded as mild (1-2), moderate (3-4), or severe (5 or more). Mean arterial pressure (MAP), heart rate (HR), and SpO2 were recorded on arrival in the operating room (baseline) and 1 min after remifentanil infusion. The incidence of RIC was 33.3% in Group R30 (13 of 39 patients), 17.9% in Group R45 (7 of 39 patients), and 5.0% in Group R60 (2 of 40 patients). Patients in Group R60 had a significantly lower incidence of RIC than those in Group R30 (P = 0.001). The MAP, HR, and SpO2 values were not significantly different between groups. When intravenous remifentanil 1.5 µg/kg was administered in pediatric patients, the incidence of RIC decreased from 33 to 5% by increasing the injection time from 30 to 60 s. Remifentanil should be administered slowly over 60 s in children to suppress cough during anesthesia induction.


Unknown cell class distinction via neural network based scattering snapshot recognition.
Neural network-based image classification is widely used in life science applications. However, it is essential to extrapolate a correct classification method for unknown images, where no prior knowledge can be utilised. Under a closed set assumption, unknown images will be inevitably misclassified, but this can be genuinely overcome choosing an open-set classification approach, which first generates an in-distribution of identified images to successively discriminate out-of-distribution images. The testing of such image classification for single cell applications in life science scenarios has yet to be done but could broaden our expertise in quantifying the influence of prediction uncertainty in deep learning. In this framework, we implemented the open-set concept on scattering snapshots of living cells to distinguish between unknown and known cell classes, targeting four different known monoblast cell classes and a single tumoral unknown monoblast cell line. We also investigated the influence on experimental sample errors and optimised neural network hyperparameters to obtain a high unknown cell class detection accuracy. We discovered that our open-set approach exhibits robustness against sample noise, a crucial aspect for its application in life science. Moreover, the presented open-set based neural network reveals measurement uncertainty out of the cell prediction, which can be applied to a wide range of single cell classifications.


Validity of controlled clinical trials of psychotherapy: findings from the NIMH Treatment of Depression Collaborative Research Program.
This research extends a series of studies that have examined the process of psychotherapy. The authors hypothesized that manual regimens of psychotherapy compared in a controlled clinical trial would overlap considerably in process and technique and that intervention strategies common to both treatments would be responsible for promoting patient change. Expert therapists developed prototypes of the ideal regimens of brief interpersonal psychotherapy and cognitive behavior therapy using the Psychotherapy Process Q-Set, an instrument designed to provide a standard language for describing treatment processes. A separate set of clinical judges then used the Psychotherapy Process Q-Set to score the actual transcripts of interpersonal psychotherapy and cognitive behavior therapy sessions conducted as part of the NIMH Treatment of Depression Collaborative Research Program. The expert prototypes were then compared with actual therapy administered in order to determine the extent to which each form of therapy conformed to its ideal prototype. Both the interpersonal psychotherapy and cognitive behavior therapy sessions adhered most strongly to the ideal prototype of cognitive behavior therapy. In addition, adherence to the cognitive behavior therapy prototype yielded more positive correlations with outcome measures across both types of treatment. Relying on brand names of therapy can be misleading. These findings suggest that the basic premise of controlled clinical trials (i.e., that the compared interventions represent separate and distinct treatments) may not have been met in the NIMH Treatment of Depression Collaborative Research Program. The implications of these findings for using controlled clinical trials to study psychotherapy are discussed.


Prescription Drug Misuse and Associated Risk Behaviors among Public High School Students in Oklahoma: Data from the 2013 Oklahoma Youth Risk Behavior Survey.
The purpose of this study was to assess the magnitude of prescription drug misuse among Oklahoma high school students, examine associated risk factors, and inform state-based prevention strategies. Data from the 2013 Oklahoma Youth Risk Behavior Survey were used for this analysis and were representative of public school students in grades 9 through 12 in Oklahoma. Variables were examined using percentages and 95% confidence intervals. The chi-square test was used to test for differences in proportions. Logistic regression was used to produce adjusted odds ratios as measures of association between selected independent variables and prescription drug misuse. Nearly one in five students had ever used a prescription drug without a doctor's prescription. While there was no statistically significant difference of prescription drug misuse by gender or grade in the bivariate analysis, after covariate adjustment, females were 1.5 times more likely than males to have misused prescription drugs and twelfth graders were 1.7 times more likely than ninth graders to have misused prescription drugs. Students who had ever taken prescription drugs without a doctor's prescription were significantly more likely than students who had never taken prescription drugs without a doctor's prescription to have engaged in current tobacco use, current binge drinking, current marijuana use, and lifetime drug use and have a higher prevalence of suicide risk.


Understanding the antitumor activity of novel hydroxysemicarbazide derivatives as ribonucleotide reductase inhibitors using CoMFA and CoMSIA.
Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed on a series of Schiff bases of hydroxysemicarbazide analogues using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods with their antitumor activities against L1210 cells. The models were generated using 24 molecules, out of which one molecule was a commercially available ribonucleotide reductase (RR) inhibitor, hydroxyurea (HU), and the predictive ability of the resulting each model was evaluated against a test set of four molecules. Maximum common substructure (MCS)-based method was used for alignment and compared with the known alignment methods. The QSAR models from both methods exhibited considerable correlative and predictive properties. Inclusion of additional descriptor ClogP improved the statistics of CoMFA model significantly. Both methods strongly suggest the necessity of lipophilicity for antitumor activity. CoMFA and CoMSIA methods predicted HU optimally, indicating a similar mechanism of action for the molecules considered for generating the models and HU to inhibit the tumor cells. The analysis of CoMFA contour maps provided insight into the possible modification of the molecules for better activity.


Dehydration of multilamellar fatty acid membranes: towards a computational model of the stratum corneum.
The level of hydration controls the cohesion between apposed lamellae of saturated free fatty acids found in the lipid matrix of stratum corneum, the outermost layer of mammalian skin. This multilamellar lipid matrix is highly impermeable to water and ions, so that the local hydration shell of its fatty acids may not always be in equilibrium with the acidity and relative humidity, which significantly change over a course of days during skin growth. The homeostasis of the stratum corneum at each moment of its growth likely requires a balance between two factors, which affect in opposite ways the diffusion of hydrophilic species through the stratum corneum: (i) an increase in water order as the lipid lamellae come in closer contact, and (ii) a decrease in water order as the fraction of charged fatty acids is lowered by pH. Herein molecular dynamics simulations are employed to estimate the impact of both effects on water molecules confined between lamellae of fatty acids. Under conditions where membrane undulations are energetically favorable, the charged fatty acids are able to sequester cations around points of contact between lamellae that are fully dehydrated, while essentially maintaining a multilamellar structure for the entire system. This observation suggests that the undulations of the fatty acid lamellae control the diffusion of hydrophilic species through the water phase by altering the positional and rotational order of water molecules in the embedded/occluded "droplets."


Miotic drugs, glaucoma, and retinal detachment.
It has been reported in the literature, and is the clinical impression of many ophthalmologists, that the use of miotic drugs and especially Phospholine Iodide increases the incidence of retinal detachment. A review of 1,000 cases of retinal detachment is reported with a breakdown of the percentage of patients who previously had glaucoma and the various drugs with which they had been treated prior to the development of their retinal detachments. The incidence of bilateral cases is also studied and conclusions are drawn as to whether or not there is any increased incidence of retinal detachment or in the bilaterality in patients who are on miotic medications.


[A case of surgical resection of lesions caused by extrahepatic seeding of hepatocellular carcinoma after percutaneous radiofrequency ablation].
We report a rare case of laparoscopic resection of lesions caused by extrahepatic seeding of hepatocellular carcinoma following percutaneous radiofrequency ablation (RFA). A 52-year-old man had undergone RFA for the treatment of hepatocellular carcinoma in April 2012. After 5 months, his serum tumor marker levels increased remarkably, and computed tomography (CT) revealed a 5 cm tumor and a small 1 cm nodule on the side of the spleen. He also had intrahepatic recurrence, but those lesions seemed to be controlled by transarterial embolization. Therefore, we performed laparoscopic resection of the extrahepatic lesion in November 2012. Histopathological examination revealed a moderately differentiated hepatocellular carcinoma. Two months later, the patient's serum tumor marker levels had decreased dramatically. The remaining intrahepatic recurrence has been stable, and we have not detected any other extrahepatic recurrence thus far. Our case supports the utility of surgical resection for the treatment of extrahepatic seeding of hepatocellular carcinoma.


[Efficacy and safety of giant emphysematous bulla volume reduction via medical thoracoscope].
Objective: To evaluate the efficacy and safety of giant emphysematous bulla (GEB) volume reduction via medical thoracoscope. Methods: This was a prospective, single-arm study conducted between July 2018 and September 2020 in Ri Zhao Hospital of Traditional Chinese Medicine. Patients who met the inclusion criteria were treated with GEB volume reduction via medical thoracoscope and were followed up to evaluate the efficacy and safety of the technique. According to comparison of preoperative and postoperative chest CT results, the self-designed evaluation criteria of imaging efficacy were as follows: complete or nearly complete disappearance of GEB (GEB volume reduction ≥90%), significant reduction of GEB (75%≤GEB volume reduction<90%), reduction of GEB (50%≤GEB volume reduction<75%) and no change (GEB volume reduction<50%). Results: A total of 47 patients were included, among whom 43 were males, with an age M (Q1, Q3) of 63.0 (55.0, 67.0). The CT results showed complete or nearly complete disappearance of GEB in 43 patients, significant reduction of GEB in 3 patients and reduction of GEB in 1 patient before discharge. The degree of dyspnea improved significantly (P<0.05). Arterial partial pressure of carbon dioxide (PaCO2) decreased from (48.2±8.4)mmHg (1 mmHg=0.133 kPa) to (45.4±7.3)mmHg (P<0.05). The 6-minute walk test (6MWT) increased from (245.6±162.4)m to (283.5±152.2)m (P<0.05). Six-month postoperative follow-up was completed in 24 patients, and CT results showed that the efficacy of volume reduction was continuous compared with that before discharge. GEB was further reduced or even disappeared in 3 of the cases. Besides, the degree of dyspnea, 6MWT (384.4±148.2)m and PaCO2 (42.7±6.6)mmHg were improved significantly (P<0.05). The oxygenation index (356.86±61.21)mmHg was significantly higher than that before surgery (295.20±67.16)mmHg and before discharge (294.50±76.69)mmHg (P<0.05). No perioperative deaths occurred. Conclusions: GEB volume can be completely eliminated or significantly reduced by this innovative technique, while PaCO2, the degree of dyspnea and exercise endurance can be significantly improved after operation. The 6-month follow-up after surgery showed that the above benefits continued, and that the oxygenation index improved significantly.


Primary healthcare professionals' knowledge, attitude and behavior regarding influenza immunization; 2006-2007 season adverse effect profile.
The objective of this study was to assess primary healthcare professionals' knowledge, attitude and behavior regarding immunization, as well as to evaluate the adverse effect profile for the 2006-2007 influenza vaccines. Influenza vaccination has been proven to have clinical and epidemiological benefits. However, its uptake in the general population and among healthcare workers has generally been suboptimal. Primary healthcare professionals of Kayseri were enrolled in the study. Of the 672 primary healthcare professionals in Kayseri, 552 (82 %) completed a questionnaire comprised of 19 questions. The study was performed in March 2007 following a campaign of the Ministry of Health of Turkey for influenza vaccination of primary healthcare workers. Of the health professionals, 67 % (370) were women and 33 % (182) were men. Overall, 420 (76.1 %; 95% confidence interval: CI = 72.3-79.5) health professionals reported that they had received influenza vaccine during the 2006-2007 influenza season. Adverse effects were reported by 157 (28.4 %) health professionals. The adverse effects reported were fever (n=57; 13.5 %), muscle pain (n=60; 14.2 %), joint pain (n=40; 9.5 %), loss of appetite (n=16; 3.8%), headache (n=41; 9.7 %), cough (n=29; 6.9 %), malaise (n=76; 18.0 %), tiredness (n=41; 9.7 %), stuffiness (n=49; 11.6 %), sneezing (n=54; 12.8 %), sore throat (n=33; 7.8 %) and others, namely erythema, edema and abscess at the vaccination site, and lymphadenopathy (n=14; 3.3 %). Our study demonstrated that primary health care professionals in our study group have been vaccinated with influenza vaccine in a reasonable percentage. There were no severe or serious adverse effects of the vaccine, the fact of which may be used to encourage both health professionals and patients of primary care (Tab. 3, Ref. 13).


Adverse reaction to tetrazepam.
Adverse reactions caused by benzodiazepines rarely occur. We present a case of a 70-year-old man who developed a maculopapular exanthema after the ingestion of tetrazepam. For his diagnosis, skin tests were performed, including prick and patch tests, not only with the benzodiazepine implicated in the reaction, but also with benzodiazepines of other groups. Single-blind oral challenge tests were also performed in the patient, in order to assess his tolerance to other benzodiazepines.


Optimisation of current injection protocol based on a region of interest.
Electrical impedance tomography has the potential to image fast neural activity associated with physiological or epileptic activity throughout the brain. These applications pose a particular challenge as expected voltage changes on the electrodes are less than 1% and geometrical constraints of the body under investigation mean that electrodes can not be evenly distributed around its boundary. Unlike other applications, however, information regarding the location of expected activity is typically available. An informative method for choosing current paths that maximise sensitivity to specific regions is desirable. Two electrode addressing protocol generation methods based on current density vectors concentrated in a region of interest have been proposed. One focuses solely on maximising its magnitude while the other considers its distribution. The quality of reconstructed images using these protocols was assessed in a simulation study conducted in a human and rat mesh and compared to the protocol that maximises distance between injecting electrodes. When implementing the protocol that focused on maximising magnitude, the current density concentrated in a region of interest increased by up to a factor of 3. When the distribution of the current was maximised, the spread of current density vectors increased by up to fivefold. For the small conductivity changes expected in the applications explored, image quality was best when implementing the protocol that maximised current density. The average image error when using this protocol was 7% better than when employing other protocols. We conclude that for fast neural EIT applications, the protocol that maximises current density is the best protocol to implement.


Modalities of Invasive Arterial Pressure Monitoring in Critically Ill Patients: A Prospective Observational Study.
Few studies assessed modalities of invasive arterial pressure monitoring (IAPM). We evaluated effects on measured values of various combinations of transducer level, catheter access site, and patient position. Prospective observational study in consecutive adults admitted to a French intensive care unit in 2009 to 2011 and fulfilling our inclusion criteria. Four combinations (B-E) of transducer level, catheter access site, and patient position were compared with a reference combination (A) (A: patient supine with all catheters in the same plane and a single transducer level (M) for zero point reference (Z) aligned on the phlebostatic axis; B: 45° head-of-bed elevation with M and Z aligned on the phlebostatic axis; C: 45° head-of-bed elevation with M aligned on the catheter access site and Z on the phlebostatic axis; D: 45° head-of-bed elevation with M and Z aligned on the catheter access site; and E: 45° head-of-bed elevation with M aligned on the phlebostatic axis and Z on the catheter access site). We included 103 patients, 68 men and 35 women, with a median age of 69 years (interquartile range [IQR], 56-78); at inclusion, 91 (88.3%) received mechanical ventilation, 45 (43.7%) catecholamines, and 66 (64.1%) sedation. The IAPM access site was femoral in 49 (47.6%) and radial in 54 (52.4%) patients, with 62 of 103 (60.2%) catheters on the right side. Measured absolute mean arterial pressure values were significantly higher with 3 study combinations (C-E) than with the reference combination (A). After adjustment, the differences versus A (median, 83 [IQR, 74-92] mm Hg) remained significant for D (median, 91 [IQR, 85-100] mm Hg, P < 0.001) and E (median, 88 [IQR, 77-99] mm Hg, P < 0.001). The difference versus A was not significant for B (median, 85 [IQR, 76-94] mm Hg, P = 0.21) or C (median, 90 [IQR, 84-100] mm Hg, P = 0.006). Several modalities used for zeroing and/or transducer leveling during IAPM may result in statistically and clinically significant overestimation of measured mean arterial pressure values. For patients in the 45° head-of-bed elevation position, aligning the Z on the phlebostatic axis provides values that are not significantly different from those obtained using the reference supine modality.


Protein-induced changes in nonplanarity of the porphyrin in nickel cytochrome c probed by resonance Raman spectroscopy.
The influence of the protein on the nonplanarity of the macrocycle for nickel(II)-reconstituted cytochrome c (NiCyt-c) has been investigated with pH-dependent resonance Raman and UV-visible absorption spectroscopy and molecular mechanics calculations. The spectra reveal that NiCyt-c near neutral pH has axially coordinated Ni, but below pH 3 and above pH 12, four-coordinate species predominate. The shape of the structure-sensitive Raman line nu10 of NiCyt-c is asymmetric and broad and it changes with pH. This broad line can be decomposed well into at least two sublines, a low-frequency line that results from a nonplanar conformer and a high-frequency line that arises from a nearly planar conformer. Upon lowering the pH from 3.0 to 1.0, the amount of the nonplanar conformer decreases relative to that of the planar conformer. The decreased nonplanarity can be accounted for in terms of the disruption of a hydrogen-bonding network in the peptide backbone upon lowering the pH. Molecular mechanics (MM) calculations on iron(III) and nickel(II) microperoxidase 5 (MP-5) as well as some model heme derivatives have been carried out in order to locate the part of the protein that causes the heme distortion observed in the X-ray crystal structures of cytochromes c. The energy-optimized structures of MP-5 and the model compounds were analyzed using the normal-coordinate structural decomposition method to specify and quantify the out-of-plane macrocyclic distortions. MM calculations for MP-5 show that two hydrogen bonds formed between the amide groups in the peptide backbone are important in maintaining the ruffled deformation of the macrocycle. All evidence presented supports the hypothesis that the nonplanar distortion of the porphyrin of cytochromes c is largely maintained by a relatively small protein segment including the cysteines, the amino acids between the cysteines, and the adjacent histidine ligand. Hydrogen bonding within the backbone of this segment is important in maintaining the conformation of the peptide that induces the porphyrin distortion.


Zonisamide, topiramate, and levetiracetam: efficacy and neuropsychological effects in alcohol use disorders.
The anticonvulsant topiramate not only decreases ethanol consumption in alcohol dependence (AD) but also may produce several adverse events including cognitive impairment. Zonisamide is a structurally related anticonvulsant that is a promising agent for the treatment of AD and may have greater tolerability than topiramate. This study evaluated the effects of zonisamide (400 mg/d) on alcohol consumption and its neurotoxic effects in subjects with AD. A double-blind placebo-controlled clinical trial was conducted using 2 comparator anticonvulsant drugs, topiramate (300 mg/d) and levetiracetam (2000 mg/d), which does not impair cognition. Study medications were administered for 14 weeks, including a 2-week taper period. Medication adherence was facilitated using Brief Behavioral Compliance Enhancement Treatment. The neurotoxicity of the study drugs was assessed using neuropsychological tests and the AB-Neurotoxicity Scale. Compared with placebo, both zonisamide and topiramate produced significant reductions in the drinks consumed per day, percent days drinking, and percent days heavy drinking. Only the percent days heavy drinking was significantly decreased in the levetiracetam group. The topiramate cell was the only group that had a significant increase on the mental slowing subscale of the Neurotoxicity Scale compared with placebo at study weeks 11 and 12. Topiramate and zonisamide both produced modest reductions in verbal fluency and working memory. These findings indicate that zonisamide may have efficacy in the treatment of AD, with effect sizes similar to topiramate. Both of these drugs produced similar patterns of cognitive impairment, although only the topiramate group reported significant increases in mental slowing.


Multi-Residue Method for Pesticides Determination in Dried Hops by Liquid Chromatography Tandem Mass Spectrometry.
In this study a multi-residue determination method for 36 pesticides in dried hops was reported. The sample preparation procedure was based on the acetate buffered QuEChERS method. A few mixtures of dispersive solid phase extraction (dSPE) sorbents consisting PSA, C18, GCB, Z-Sep and Z-Sep+ were investigated to clean-up the supernatant and minimize matrix co-extractives. The degree of clean-up was assessed by gravimetric measurements, which showed the best results for mixtures containing the Z-Sep+ sorbent. This is the first study to apply Z-Sep+ sorbent for hops material and the first to improve the method for pesticide residues determination in hops. Samples were analysed using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and the procedure was validated according to the SANTE/11813/2017 document at four concentration levels: 0.02, 0.05, 0.1 and 1 mg/kg. The limits of quantification (LOQ) were in the range of 0.02-0.1 mg/kg. For all active substances, the trueness (recovery) ranged from 70 to 120% and the precision (RSDr) value was <20%. Specificity, linearity and matrix effect were also evaluated. The validated method was applied to the analysis of 15 real dried hop samples and the relevant data on detected residues were included.


Race-, gender- and age-specific differences in dietary micronutrient intakes of US children.
Race-, gender- and age-specific differences in dietary micronutrient intakes of 1- to 10-year-old US children were evaluated. Three-day, dietary intakes from the US Department of Agriculture's Continuing Survey of Food Intakes by Individuals were evaluated. Data from 1895 children (967 males, 928 females; 1,540 Whites, 355 Blacks) who resided in the 48 conterminous states were analyzed. Micronutrient intakes, intakes as percent of the Recommended Dietary Allowance (RDA) and percent of children who consumed < or =67% of the RDA were computed. Black males compared with White males, Black females compared with White females and White females compared with White males had significantly lower dietary intakes for several micronutrients. More Black males than White males had intakes < or =67% of the RDA for vitamin E, calcium and zinc. Blacks and female children were at a greater risk for vitamin A, vitamin E, calcium, iron and zinc deficiency.


Bidirectional signaling between the cytoskeleton and integrins.
Clustering of integrins into focal adhesions and focal complexes is regulated by the actin cytoskeleton. In turn, actin dynamics are governed by Rho family GTPases. Integrin-mediated adhesion activates these GTPases, triggering assembly of filopodia, lamellipodia and stress fibers. In the past few years, signaling pathways have begun to be identified that promote focal adhesion disassembly and integrin dispersal. Many of these pathways result in decreased myosin-mediated cell contractility.


The value of the new scoring system for predicting neoplastic pericarditis in the patients with large pericardial effusion.
Early recognition of neoplastic pericarditis (npe) is crucial for the planning of subsequent therapy. The aim of the present study was to construct the scoring system assessing the probability of npe, in the patients requiring pericardial fluid (pf) drainage due to large pericardial effusion. One hundred forty-six patients, 74 males and 72 females, entered the study. Npe based on positive pf cytology and/or pericardial biopsy specimen was recognised in 66 patients, non-npe in 80. Original scoring system was constructed based on parameters with the highest diagnostic value: mediastinal lymphadenopathy on chest CT scan, increased concentration of tumour markers (cytokeratin 19 fragments-Cyfra 21-1 and carcinoembryonic antigen-CEA) in pf, bloody character of pf, signs of imminent cardiac tamponade on echocardiography and tachycardia exceeding 90 beats/min on ECG. Each parameter was scored with positive or negative points depending on the positive and negative predictive values (PPV, NPV). The area under curve (AUC) for the scoring system was 0.926 (95%CI 0.852-0.963) and it was higher than AUC for Cyfra 21-1 0.789 (95%CI 0.684-0.893) or CEA 0.758 (95%CI 0.652-0.864). The score optimally discriminating between npe and non-npe was 0 points (sensitivity 0.84, specificity 0.91, PPV 0.9, NPV 0.85). Despite chest CT and tumour marker evaluation in pericardial fluid were good discriminators between npe and non-npe, the applied scoring system further improved the predicting of neoplastic disease in the studied population.


Management of a nonreactive nonstress test in a twin gestation. A case report.
The increased risk associated with multiple gestation requires antepartum fetal surveillance with electronic fetal heart rate monitoring. Occasionally the nonstress test is abnormal in one fetus. We reviewed such a case for the pertinent questions about management of a nonreactive nonstress test in a twin gestation. From the case and the literature we formulated a protocol for management.


Pharmacologic blockade of chloride channel synergistically enhances apoptosis of chemotherapeutic drug-resistant cancer stem cells.
1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) is the most commonly used chemotherapeutic agent in the treatment of human glioblastoma multiforme (GBM). However, BCNU chemotherapy fails due to subpopulations of intrinsic resistant-cells within the tumor mass. In our previous study, we dissociated BCNU-resistant cancer stem cells (CSCs) and observed the over-expression of multiple ion channel genes related to drug efflux. In the present study, we identified chloride intracellular channel 1 (CLIC1) in dissociated-BCNU-resistant CSCs using 2-DE and MALDI-TOF/MS analysis. To develop the specific target therapy of BCNU-resistant CSCs, we evaluated the drug-sensitivity of these CSCs using the chloride channel blocker, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). When combined with BCNU, DIDS synergistically increased the apoptotic events of BCNU-resistant CSCs in vitro and augmented BCNU sensitivity ex vivo. These findings suggest that CLIC1 is involved in the resistance of BCNU-resistant CSCs and BCNU/DIDS combined-therapy can provide valuable insight for promoting apoptosis or sensitizing glioblastomas to BCNU chemotherapy.