Zinc ion enhances GABA tea-mediated oxidative DNA damage.
GABA tea is a tea product that contains a high level of γ-aminobutyric acid (GABA). Previous study has demonstrated a synergistic effect of GABA tea and copper ions on DNA breakage. This study further explored whether zinc (Zn), a nonredox metal, modulated DNA cleavage induced by GABA tea extract. In a cell-free system, Zn(2+) significantly enhanced GABA tea extract and (-)-epigallocatechin-3-gallate (EGCG)- or H(2)O(2)-induced DNA damage at 24 h of incubation. Additionally, low dosages of GABA tea extract (1-10 μg/mL) possessed pro-oxidant activity to increase H(2)O(2)/Zn(2+)-induced DNA cleavage in a dose-dependent profile. By use of various reactive oxygen scavengers, it was observed that glutathione, catalase, and potassium iodide effectively inhibited DNA degradation caused by the GABA tea extract/H(2)O(2)/Zn(2+) system. Moreover, the data showed that the GABA tea extract itself (0.5-5 mg/mL) could induce DNA cleavage in a long-term exposure (48 h). EGCG, but not the GABA tea extract, enhanced H(2)O(2)-induced DNA cleavage. In contrast, GABA decreased H(2)O(2)- and EGCG-induced DNA cleavage, suggesting that GABA might contribute the major effect on the antioxidant activity of GABA tea extract. Furthermore, a comet assay revealed that GABA tea extract (0.25 mg/mL) and GABA had antioxidant activity on H(2)O(2)-induced DNA breakage in human peripheral lymphocytes. Taken together, these findings indicate that GABA tea has the potential of both pro-oxidant and antioxidant. It is proposed that a balance between EGCG-induced pro-oxidation and GABA-mediated antioxidation may occur in a complex mixture of GABA tea extract.


Glycemic index of starch affects nitrogen retention in grower pigs.
Three studies were performed to examine the effect of starch and protein digestion rates on N retention in grower pigs. In Exp. 1, the glycemic index (GI) of corn, a malting barley, and a slow-rumen-degradable barley (SRD-barley) were measured using 6 barrows (BW = 18.0 ± 0.5 kg). The GI of malting barley was greater (P < 0.05) than that of SRD-barley (71.1 vs. 49.4), and the GI of both barley cultivars was less (P < 0.05) than that of corn (104.8). In Exp. 2, the standardized ileal digestibility of AA and DE content of the 3 ingredients were determined using 5 ileal-cannulated barrows (BW = 20.7 ± 2.3). The apparent total-tract energy digestibility values of corn (86.1%) and malting barley (85.7%) were greater (P < 0.05) than that of SRD-barley (82.3%). The standardized ileal digestibility of Lys was 94.0, 92.6, and 92.4% for corn, malting barley, and SRD-barley, respectively, and did not differ among grains. In Exp. 3, 6 diets were formulated to equal DE (3.40 Mcal/kg), standardized ileal digestibility of Lys (8.6 g/kg), starch (424.9 g/kg), and digestible CP (180.0 g/kg) using the values obtained in Exp. 2. Three GI [high (corn), medium (malting barley), and low (SRD-barley)] and 2 rates of protein digestion [rapid (soy protein hydrolysate) and slow (soy protein isolate)] were tested in a 3 × 2 factorial arrangement with 36 barrows (BW = 32.2 ± 2.5 kg). Pigs were fed 3.0 times the maintenance energy requirement daily in 2 meals for 2 wk and were housed in metabolic crates to collect feces and urine separately. At the end of the study, intestinal contents were collected from 4 equal-length segments of the small intestine. The percentage of unabsorbed CP in segment 1 relative to dietary CP was greater (P < 0.05) for the soy protein isolate diet than for the soy protein hydrolysate diet (170.3 vs. 116.5%). The percentages of unabsorbed starch in segments 1 and 2 were greater (P < 0.05) for the SRD-barley diet than for the malting barley or corn diet. Nitrogen intake and fecal N excretion were greater (P < 0.05) for pigs fed the malting barley and SRD-barley diets than for pigs fed the corn diet. Urinary N excretion was greater (P < 0.05) for pigs fed the SRD-barley diet than for pigs fed the corn or malting barley diet. Pigs fed slowly digestible starch (SRD-barley; 46.6%) had less (P < 0.05) net N retention than pigs fed corn or malting barley (54.7 and 54.1%, respectively). In conclusion, slowly digestible starch sources such as SRD-barley may not be suitable to support maximum protein deposition in restricted-fed grower pigs.


The N-terminal region of the transmembrane domain of human erythrocyte band 3. Residues critical for membrane insertion and transport activity.
We studied the role of the N-terminal region of the transmembrane domain of the human erythrocyte anion exchanger (band 3; residues 361-408) in the insertion, folding, and assembly of the first transmembrane span (TM1) to give rise to a transport-active molecule. We focused on the sequence around the 9-amino acid region deleted in Southeast Asian ovalocytosis (Ala-400 to Ala-408), which gives rise to nonfunctional band 3, and also on the portion of the protein N-terminal to the transmembrane domain (amino acids 361-396). We examined the effects of mutations in these regions on endoplasmic reticulum insertion (using cell-free translation), chloride transport, and cell-surface movement in Xenopus oocytes. We found that the hydrophobic length of TM1 was critical for membrane insertion and that formation of a transport-active structure also depended on the presence of specific amino acid sequences in TM1. Deletions of 2 or 3 amino acids including Pro-403 retained transport activity provided that a polar residue was located 2 or 3 amino acids on the C-terminal side of Asp-399. Finally, deletion of the cytoplasmic surface sequence G(381)LVRD abolished chloride transport, but not surface expression, indicating that this sequence makes an essential structural contribution to the anion transport site of band 3.


Altered cardiovascular responses in mice lacking the M(1) muscarinic acetylcholine receptor.
Although the M(2) muscarinic acetylcholine receptor (mAChR) is the predominant functional mAChR subtype in the heart, some responses of the cardiovascular system to acetylcholine (ACh) may be mediated by other mAChR subtypes. The potential effect of M(1) mAChR on heart function was investigated using M(1) knockout (M(1)-KO) mice. In vivo cardiodynamic analysis showed that basal values of heart rate (HR), developed left ventricular pressure (DLVP), left ventricular dP/dt(max) (LV dP/dt(max)), and mean blood pressure (MBP) were similar between wild-type (WT) and M(1)-KO mice. Injection of the putative M(1)-selective agonist 4-(m-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium (McN-A-343) produced an increase in LV dP/dt(max), DLVP, HR, and MBP in WT mice but did not affect hemodynamic function in the M(1)-KO mice. The stimulatory effect of McN-A-343 in WT mice was blocked by pretreatment with propranolol, indicating that stimulation of the M(1) mAChRs on sympathetic postganglionic neurons evoked release of catecholamines. Intravenous injection of ACh in both WT and M(1)-KO mice caused atrioventricular conduction block, without a significant change in the frequency of atrial depolarization, or atrial fibrillation. Immunoprecipitation and reverse transcriptase-polymerase chain reaction failed to detect the expression of M(1) mAChR in cardiac tissue from WT mice. The carbachol-induced increase of phospholipase C activity in cardiac tissues was not different between WT and M(1)-KO mice. These results demonstrate that 1) activation of M(1) mAChR subtype on sympathetic postganglionic cells results in catecholamine-mediated cardiac stimulation, 2) M(1) mAChR is not expressed in mouse heart, and 3) administration of ACh to mice induces arrhythmia.


Absorption Saturation Effects on High-Power CO(2) Laser Beam Transmission.
A theoretical and numerical investigation is made of the effect on a beam of 10.6-microm radiation of absorption saturation of the CO(2) molecules in its path. Saturation of the CO(2) absorption cross section sets in under irradiation at high power levels when induced emission balances the resonant absorption. We show by means of computer plots that soon after a high-power beam with a parabolic profile is turned on, a caustic may form near its boundary as a result of CO(2) absorption saturation in the central portion. At high altitudes we show that absorption saturation can lead to enhanced transmission over long distances.


Old Materials for New Functions: Recent Progress on Metal Cyanide Based Porous Materials.
Cyanide is the simplest ligand with strong basicity to construct open frameworks including some of the oldest compounds reported in the history of coordination chemistry. Cyanide can form numerous cyanometallates with different transition metal ions showing diverse geometries. Rational design of robust extended networks is enabled by the strong bonding nature and high directionality of cyanide ligand. By virtue of a combination of cyanometallates and/or organic linkers, multifunctional framework materials can be targeted and readily synthesized for various applications, ranging from molecular adsorptions/separations to energy conversion and storage, and spin-crossover materials. External guest- and stimuli-responsive behaviors in cyanide-based materials are also highlighted for the development of the next-generation smart materials. In this review, an overview of the recent progress of cyanide-based multifunctional materials is presented to demonstrate the great potential of cyanide ligands in the development of modern coordination chemistry and material science.


Report of the ethics committee, 2012.
In accordance with the bylaws of the American Psychological Association (APA), the Ethics Committee reports regularly to the membership regarding the number and types of ethics matters investigated and the major programs undertaken. In 2012, ethics adjudication, ethics education and consultation, and special projects were activities of the Ethics Committee. Issues, activities, and programs regarding diversity and minority group outreach are also discussed.


Dynamic measurements of aqueous lanthanide triflate-catalyzed reactions using luminescence decay.
There is tremendous interest in water-compatible lanthanide triflate-based catalysts for carbon-carbon bond forming reactions; however, poor understanding of their aqueous mechanism severely limits the ability to increase the utility of these catalysts. Here, we report dynamic measurements of the water-coordination number of lanthanide triflate-based catalysts using luminescence-decay measurements in a range of aqueous systems. This unique characterization method is a reliable, convenient, and fast approach to analyze lanthanide-based catalysts in aqueous systems.


Drug withdrawals in the United States: a systematic review of the evidence and analysis of trends.
There have been a number of highly publicized safety-based drug withdrawals in the United States in recent years. We conducted a review of drugs withdrawn since 1993 and examined trends in drug withdrawals. Our objective was to determine the frequency and characteristics of withdrawn drugs and trends since 1993, and to discuss the implications of the findings. We found that a mean of 1.5 drugs per year have been withdrawn since 1993, and that the number of withdrawals has not increased over time. However, some recent drug withdrawals have impacted large numbers of people. The rate of withdrawals alone is not an adequate measure of the status of drug safety in the US, and there is a serious dearth of data that can be used to examine the impact of drug withdrawals. Although drug withdrawals are an important issue to address, drug safety policies need to be developed within the broader context of drug safety and effectiveness. A comprehensive approach will be needed to address the improvement of drug safety. We propose improvements to the evidence base to increase drug safety and assess how new scientific evidence can be incorporated into drug safety efforts.


Priority Actions to Advance Population Sodium Reduction.
High sodium intake is estimated to cause approximately 3 million deaths per year worldwide. The estimated average sodium intake of 3.95 g/day far exceeds the recommended intake. Population sodium reduction should be a global priority, while simultaneously ensuring universal salt iodization. This article identifies high priority strategies that address major sources of sodium: added to packaged food, added to food consumed outside the home, and added in the home. To be included, strategies needed to be scalable and sustainable, have large benefit, and applicable to one of four measures of effectiveness: (1) Rigorously evaluated with demonstrated success in reducing sodium; (2) suggestive evidence from lower quality evaluations or modeling; (3) rigorous evaluations of similar interventions not specifically for sodium reduction; or (4) an innovative approach for sources of sodium that are not sufficiently addressed by an existing strategy. We identified seven priority interventions. Four target packaged food: front-of-pack labeling, packaged food reformulation targets, regulating food marketing to children, and taxes on high sodium foods. One targets food consumed outside the home: food procurement policies for public institutions. Two target sodium added at home: mass media campaigns and population uptake of low-sodium salt. In conclusion, governments have many tools to save lives by reducing population sodium intake.


DNA deletion associated with hereditary neuropathy with liability to pressure palsies.
Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder that causes episodes of focal demyelinating neuropathy following minor trauma to peripheral nerves. We assign the HNPP locus to chromosome 17p11.2 and demonstrate the presence of a large interstitial deletion associated with this disorder in three unrelated pedigrees. De novo deletion is documented in one pedigree. The deleted region appears uniform in all pedigrees and includes the gene for peripheral myelin protein 22 (PMP-22), suggesting that underexpression of PMP-22 may cause HNPP. The deletion in HNPP spans approximately 1.5 Mb and includes all markers that are known to map within the Charcot-Marie-Tooth neuropathy type 1A (CMT1A) duplication. Furthermore, the breakpoints in HNPP and CMT1A map to the same intervals in 17p11.2, suggesting that these genetic disorders may be the result of reciprocal products of unequal crossover.


The Effect of Peroneal Muscle Strength on Functional Outcomes After the Modified Broström Procedure for Chronic Ankle Instability.
Although the peroneal muscles are known to be the major dynamic lateral stabilizers of the ankle, little information is available regarding the change in muscle strength and relation with the outcomes after lateral ligament repair surgery. The purpose of this study was to identify the effects of peroneal strength on the validated functional outcome measures after the modified Broström procedure (MBP) for chronic ankle instability. Forty-one patients (41 ankles) who underwent MBP using suture anchors were eligible and followed up to 2 years postoperatively. Functional evaluation consisted of the Foot and Ankle Outcome Score (FAOS), and Foot and Ankle Ability Measure (FAAM). The changes of peroneal strength were evaluated using an isokinetic dynamometer. Differences in the functional outcomes between the 3 groups divided according to the recovery rate of peroneal strength were analyzed. Peak torque and total work for eversion in 60 degrees/s angular velocity significantly improved from a mean 8.1 and 5.2 Nm preoperatively to 11.4 and 6.9 Nm at postoperative 2 years, respectively ( P < .001, P = .038). The deficit ratio of peak torque for eversion significantly improved from a mean 38.6% to 17.4%, and a significant side-to-side difference was found ( P = .011). There were no significant differences in FAOS, FAAM, and measurements of stress radiograph between the 3 groups. Although restoration of peroneal strength postoperatively was about 82.6% of the unaffected ankle, patient-reported function in daily and sport activities were satisfactorily improved. Postoperative isokinetic strength of the peroneals demonstrated no statistically significant effects on the functional outcomes after MBP. Level III, prospective comparative case series.


Differentiation-linked expression of prothymosin alpha gene in human myeloid leukemic cells.
Prothymosin alpha (ProT alpha) is a nuclear protein related to cell proliferation. Its gene is highly activated during postnatal development at stages containing many proliferating but also differentiating cells. In this report, a study on ProT alpha gene expression during differentiation of human myeloid leukemic (HL-60) cells was undertaken to analyze the possible association of ProT alpha to cell differentiation. When HL-60 cells were induced to differentiate to granulocytes (using retinoic acid) or monocyte/macrophages (using 12-O-tetradecanoylphorbol-13-acetate), a marked down-regulation in the levels of ProT alpha transcript was found. When cell division of immature HL-60 cells was interrupted by either treatment with hydroxyurea or serum starvation, ProT alpha gene expression was not significantly altered. These findings suggest that loss of ProT alpha mRNA in induced HL-60 cells is a differentiation-related event. Examination of the stability of ProT alpha mRNA showed that the stabilization of the ProT alpha transcript is differentially regulated in the two HL-60 lineages. Nuclear run-on experiments revealed that during HL-60 differentiation, the transcriptional activity of the ProT alpha gene does not experience significant variations.


Oestrogen modulation of the effect of 8-OH-DPAT on prepulse inhibition: effects of aromatase deficiency and castration in mice.
The aim of this study was to investigate the interaction of sex steroid hormones, particularly oestrogen, in the regulation of prepulse inhibition (PPI) by serotonin-1A (5-HT1A) receptors. We studied aromatase knockout (ArKO) mice, which are unable to produce oestrogen but have high levels of testosterone, and the effects of castration. Treatment of male ArKO mice with the 5-HT1A receptor agonist, 8-hydroxy-dipropyl-aminotetralin (8-OH-DPAT), caused an increase in PPI that was significantly greater than in male wild-type controls. Castration of male mice caused a significant enhancement of the effect of 8-OH-DPAT in control mice; however, there was no change in the effect of this drug in ArKO mice. There was no significant effect of 8-OH-DPAT on PPI in either female ArKO or wild-type controls. In all experiments, the effects of 8-OH-DPAT on startle were not different between the groups. [3H]8-OH-DPAT autoradiography showed no differences in 5-HT1A receptor binding densities in areas of the forebrain, hippocampus or raphe region that could explain the PPI results. These data show that the absence of oestrogen in male ArKO mice leads to a greater effect of 5-HT1A receptor stimulation on PPI. This effect can be mimicked in male control mice by castration. The differential involvement of oestrogen and testosterone in these animal models is discussed.


The Role of Active Video-Accompanied Exercises in Improvement of the Obese State in Children: A Prospective Study from Turkey.
The aim of this study was to determine the effects of active video games and music-accompanied aerobic and callisthenic exercises on body mass index (BMI), body fat ratio, physical performance tests, psychosocial status, and self-respect in overweight and obese adolescents. Fifty (21 males and 29 females) slightly overweight and obese participants with no chronic disorder and of an average age of 12.16±0.99 years were included in the study. The percentile values for BMI, triceps skinfold thickness, waist circumference measurements, and physical performance tests were evaluated. The effects of obesity on psychological wellness were evaluated using the depression scale for children (DSC) and the Piers-Harris Children's Self-Concept Scale for self-esteem. Following these evaluations, the participants were subjected to an exercise program in five groups of 10 people, 3 days a week for a duration of 8 weeks. Each exercise session lasted 45 minutes. Participants were re-evaluated at the end of the exercise program. The data collected both before and after the exercise program were analyzed using the SPSS 18.0 program. According to BMI reference values, 28% of the 50 participants (n=14; 6 males and 8 females) were assessed to be overweight and 72% to be obese (n=36; 15 males and 21 females). Following the exercise program, 14% of the participants (n=7; 3 males and 4 females) were assessed as normal, 46% (n=23; 14 males and 9 female) as slightly overweight, and 40% (n=20; 4 male and 16 female) as obese. It was determined that the decrease in BMI values (p<0.05) was higher in male participants than in female participants and that the frequency of obesity was higher in the females. A statistically significant decrease in BMI values was found after the exercise program (p<0.01). Following the exercise program, statistically significant differences have also been observed in the self-esteem (p<0.01), psychological wellness (p=0.025), triceps skinfold thickness, as well as in waist circumference and BMI values of the participants compared to the pre-exercise phase (p<0.01). An exercise program applied with active video games was found to have positive effects on the obese state as well as on the psychosocial status and self-esteem of obese individuals, indicating that exercise and physical activity have an important role in improvement of the obese state in childhood as well as having positive contributions to self-esteem and psychological wellness state.


Dynamics of metastable breathers in nonlinear chains in acoustic vacuum.
The study of the dynamics of one-dimensional chains with both harmonic and nonlinear interactions, as in the Fermi-Pasta-Ulam and related problems, has played a central role in efforts to identify the broad consequences of nonlinearity in these systems. Nevertheless, little is known about the dynamical behavior of purely nonlinear chains where there is a complete absence of the harmonic term, and hence sound propagation is not admissible, i.e., under conditions of "acoustic vacuum." Here we study the dynamics of highly localized excitations, or breathers, which are known to be initiated by the quasistatic stretching of the bonds between adjacent particles. We show via detailed particle-dynamics-based studies that many low-energy pulses also form in the vicinity of the perturbation, and the breathers that form are "fragile" in the sense that they can be easily delocalized by scattering events in the system. We show that the localized excitations eventually disperse, allowing the system to attain an equilibrium-like state that is realizable in acoustic vacuum. We conclude with a discussion of how the dynamics is affected by the presence of acoustic oscillations.


Adaptation of an ELISA assay for detection of IgG2a responses against therapeutic monoclonal antibodies in a mouse immunization model.
Biotherapeutic monoclonal antibodies (mAb) play important roles in clinical medicine but their potential to elicit immune responses in patients remains a major issue. In a study designed to investigate the effect of aggregation on immunogenic responses, mice were immunized with two monoclonal antibodies (mAb1 and mAb2). Serum levels of total IgG, IgG1, and IgG2a were measured by ELISA. An anti-mouse IgG2a monoclonal detection antibody cross-reacted with mAb2 but not mAb1, leading to high background when the ELISA plate was coated with mAb2. The problem was solved by use of a goat anti-mouse IgG2a polyclonal antibody that demonstrated the required specificity. IgG2a responses were similar for monomer- or aggregate-coated ELISA plates. The results demonstrate the importance of assessment of the specificity of individual reagents when measuring antibody responses against therapeutic antibodies by ELISA.


The devitrification of artificial fibers: a multimethodic approach to quantify the temperature-time onset of cancerogenic crystalline phases.
A variety of artificial fibers extensively employed as lining in high-temperature apparatus may undergo a devitrification process that leads to significant changes in the chemical-physical properties of the materials. Among them, the crystallization of carcinogenic minerals, such as cristobalite, has already been documented for alumino-silicate ceramic fibers. Five fibrous samples with different compositions were treated over a wide range of temperatures (20-1500°C) and times (24-336 h) to investigate the rate and the crystalline phases that are formed as well their onset temperatures. The new phases were characterized by using a multimethodic approach: phase transformations were monitored together with thermal analysis and the new phases were investigated by using X-ray powder diffraction analysis. The crystalline:amorphous ratio was monitored by Rietveld refinement of X-ray diffraction data. Scanning electron microscopy was used to study the effect of heat treatments on the morphology of fibers, and the nanostructures were investigated by transmission electron microscopy (TEM). The results show that the main crystalline phases are cristobalite, diopside, mullite, and zirconia. The onset of cristobalite was observed at temperature lower than that thermodynamically expected. The TEM analysis showed that protostructures were present in the material vitrified from sol-gel-derived products, which can act as crystallization nuclei. The study shows that the devitrification leads to health hazard due to the formation of inhalable powder of cancerogenic crystalline phases.


Patient Safety and Quality Improvement Education in Otolaryngology Residency: Preliminary Look at a Module-Based Approach.
Since publication of the Institute of Medicine's report To Err Is Human in 1999, patient safety and health care quality have become hot topics in the parlance of modern medical care. The Accreditation Council for Graduate Medical Education now requires integration of these topics into resident education, with evidence of trainee involvement in Patient Safety and Quality Improvement (PSQI) projects. Research in other disciplines indicates that interactive, experiential learning leads to the highest quality PSQI education. Otolaryngology as a field has been slow to adopt these changes into its residency curricula due to competing educational demands and lack of faculty expertise. The author reports preliminary experience with integration of an online module-based curriculum that addresses both of these issues.


Comparison of train-of-four and best clinical assessment during continuous paralysis.
Train-of-four (TOF) monitoring is recommended in published guidelines during use of continuous-infusion neuromuscular blocking agents (NMB) in the intensive care unit (ICU). To test that recommendation, dual protocols were established in a medical ICU after intensive nursing education. Paralyzed patients received either TOF monitoring with a goal of three twitches or best clinical assessment while receiving atracurium by continuous infusion. Demographics and mean duration of paralysis of 20 patients in the TOF group were no different than that of the 16 patients in the best clinical assessment group. Although most patients demonstrated atracurium tolerance over time, there was no difference between groups in total mg (+/- SEM) infused (10,460 +/- 2,409 versus 9,201 +/- 3,237) or mean microgram/kg/min (15.2 +/- 1.5 versus 12.0 +/- 1.1). The time to clinical recovery was no different between groups (50 +/- 10 versus 45 +/- 12 min). Two complications occurred in the TOF group, with pulmonary emboli despite prophylaxis and an unrecognized cerebrovascular accident in one patient each. We conclude that careful titration of NMB using clinical bedside markers should remain the standard of care with these drugs.


Histological findings following the use of a space-making device for bone reformation and implant integration in the maxillary sinus of primates.
Previous studies have shown that membrane elevation results in predictable bone formation in the maxillary sinus provided that implants can be placed as tent poles. In situations with an extremely thin residual crest which impairs implant placement, it is possible that a space-making device can be used under the sinus membrane to promote bone formation prior to placement of implants. The present study was conducted to test the hypothesis that the use of a space-making device for elevation of the sinus membrane will result in predictable bone formation at the maxillary sinus floor to allow placement of dental implants. Eight tufted capuchin primates underwent bilateral sinus membrane elevation surgery, and a bioresorbable space-making device, about 6 mm wide and 6 mm in height, was placed below the elevated membrane on the sinus floor. An oxidized implant (Nobel Biocare AB, Gothenburg, Sweden) was installed in the residual bone protruding into the created space at one side while the other side was left without an implant. Four animals were sacrificed after 6 months of healing. The remaining four animals received a second implant in the side with a space-making device only and followed for another 3 months before sacrifice. Implant stability was assessed through resonance frequency analysis (RFA) using the Osstell (Osstell AB, Gothenburg, Sweden) at installation, 6 months and 9 months after the first surgery. The bone-implant contact (BIC) and bone area inside the threads (BA) were histometrically evaluated in ground sections. Histologically there were only minor or no signs of bone formation in the sites with a space-making device only. Sites with simultaneous implant placement showed bone formation along the implant surface. Sites with delayed implant placement showed minor or no bone formation and/or formation of a dense fibrous tissue along the apical part of the implant surface. In the latter group the apical part of the implant was not covered with the membrane but protruded into the sinus cavity. The use of a space-making device, with the design used in the present study, does not result in bone formation at the sinus floor. However, membrane elevation and simultaneous placement of the device and an implant does result in bone formation at the implant surface while sites with implants placed 6 months after membrane elevation show only small amounts of bone formation. It is suggested that lack of stabilization of the device and/or a too extensive elevation of the membrane may explain the results.


SOX Transcription Factors in Endothelial Differentiation and Endothelial-Mesenchymal Transitions.
The SRY (Sex Determining Region Y)-related HMG box of DNA binding proteins, referred to as SOX transcription factors, were first identified as critical regulators of male sex determination but are now known to play an important role in vascular development and disease. SOX7, 17, and 18 are essential in endothelial differentiation and SOX2 has emerged as an essential mediator of endothelial-mesenchymal transitions (EndMTs), a mechanism that enables the endothelium to contribute cells with abnormal cell differentiation to vascular disease such as calcific vasculopathy. In the following paper, we review published information on the SOX transcription factors in endothelial differentiation and hypothesize that SOX2 acts as a mediator of EndMTs that contribute to vascular calcification.


Insights into Actin-Myosin Interactions within Muscle from 3D Electron Microscopy.
Much has been learned about the interaction between myosin and actin through biochemistry, in vitro motility assays and cryo-electron microscopy (cryoEM) of F-actin, decorated with myosin heads. Comparatively less is known about actin-myosin interactions within the filament lattice of muscle, where myosin heads function as independent force generators and thus most measurements report an average signal from multiple biochemical and mechanical states. All of the 3D imaging by electron microscopy (EM) that has revealed the interplay of the regular array of actin subunits and myosin heads within the filament lattice has been accomplished using the flight muscle of the large water bug Lethocerus sp. The Lethocerus flight muscle possesses a particularly favorable filament arrangement that enables all the myosin cross-bridges contacting the actin filament to be visualized in a thin section. This review covers the history of this effort and the progress toward visualizing the complex set of conformational changes that myosin heads make when binding to actin in several static states, as well as the fast frozen actively contracting muscle. The efforts have revealed a consistent pattern of changes to the myosin head structures as determined by X-ray crystallography needed to explain the structure of the different actomyosin interactions observed in situ.


Electrogenic transport of glucose in the normal upper duodenum. II. Unstirred water layer and estimation of real transport constants.
The thickness of the unstirred water layer in the normal upper duodenum was measured in 11 healthy volunteers. We used the technique of simultaneous intestinal perfusion and measurement of the corresponding transmucosal potential differences (pd). The unstirred layer was calculated from the half time required to establish an Na+ diffusion potential across this layer. At a flow rate of 17 ml/min the thickness was 351 +/- 13 microns (mean +/- 1 SEM). The level increased significantly as the flow rate was reduced. The results were used to calculate estimates of the real transport constants, which describe the carrier-mediated electrogenic transport of glucose in the normal upper duodenum. Pdrealmax was calculated to be 1.1 +/- 0.15 mV, Jrealmax 6.6 nmol/cm2 X sec, and Krealm 25.8 mM. The origin of the transport-related potential change during glucose absorption was examined. It is suggested that about 60% of the total measured potential response may be attributed to a Na+ diffusion potential across the intestinal unstirred water layer.


Method for detecting the signature of noise-induced structures in spatiotemporal data sets.
Spatiotemporal stochastic resonance (STSR) is a phenomenon, where the stability of spatial patterns in an extended dynamical system displays a resonance-type dependence on the noise amplitude with the patterns being optimal at intermediate noise level. This dynamical behavior has been found in theoretical systems as well as in biochemical processes, where the noise level has been controlled externally. However, it is an open question how to identify the signature of a spatiotemporal stochastic resonance in a natural system, e.g., in ecology, when the noise amplitude is not known. This question is addressed in the present paper. We provide analysis tools, which allow to reconstruct the noise intensity in a spatiotemporal data set from the data alone. These tools are based on nearest-neighbor considerations inspired by cellular automata and are an appropriate method for detecting STSR, when combined with some measure of spatial order. As a test of our analysis tools, we apply them to sample data generated by four theoretical model systems. We show explicitly that without knowledge of the theoretical value of the noise amplitude for those systems displaying STSR the corresponding resonance curve can be reconstructed from the data alone. In addition, the other (nonresonant) cases are properly identified by our method with no resonance curve being found.


Sexual harassment among adolescents of different sexual orientations and gender identities.
This article examines (a) variation in rates of sexual harassment across mode (e.g., in-person, online) and type of harassment, (b) the impact of sexual harassment (i.e., distressing vs. non-distressing), and (c) how sexual harassment is similarly and differently experienced across sexual orientation and gender identity groups. Data were collected as part of the Teen Health and Technology online survey of 5,907 13 to 18 year-old Internet users in the United States. Past year sexual harassment was reported by 23-72% of youth, depending upon sexual orientation, with the highest rates reported by lesbian/queer girls (72%), bisexual girls (66%), and gay/queer boys (66%). When examined by gender identity, transgender youth reported the highest rates of sexual harassment - 81%. Overall, the most common modes for sexual harassment were in-person followed by online. Distress in the form of interference with school, family, and/or friends; creating a hostile environment; or being very/extremely upset was reported by about half of the sexually harassed bisexual girls and lesbian/queer girls, 65% of the gender non-conforming/other gender youth, and 63% of the transgender youth. Youth with high social support and self-esteem were less likely to report sexual harassment. Findings point to the great importance of sexual harassment prevention for all adolescents, with particular emphasis on the unique needs and experiences of youth of different sexual orientations and gender identities. Socio-emotional programs that emphasize self-esteem building could be particularly beneficial for reducing the likelihood of victimization and lessen the impact when it occurs.


[Laparoscopy in emergency abdominal surgery].
To evaluate the possibilities of laparoscopy in the diagnosis and treatment of acute abdominal surgical diseases. A retrospective analysis of laparoscopic procedures in 4655 patients with confirmed or suspected acute abdominal surgical diseases for the period 2008-2017 was performed. Laparoscopy was applied to confirm or to determine unclear diagnosis. Diagnosis was established and confirmed in 4526 (97.2%) patients. Advisability of laparoscopic surgery was confirmed in 3091 (68.3%) patients, laparotomy - in 491 (10.8%) patients. Surgical treatment was not required in 944 (20.9%) patients. Laparoscopic procedures were performed in 3050 (98.7%) patients, 41 (1.3%) patients required conversion to laparotomy. Laparoscopic approach failed to define diagnosis in 129 (2.8%) patients that required conversion to diagnostic laparotomy. Laparoscopic was valuable to establish the diagnosis and determine surgical strategy, diagnose concomitant diseases, perform operations including simultaneous ones.


Management of radiation-induced head and neck injury.
Toxicity from H&N cancer irradiation is complex and multifactorial. The nature and severity of the side effect profile for a given patient result from the interplay of patient-related, tumor-related, and treatment-factors. Among the side effects studied, skin toxicity and mucositis represent the most common acute effects of irradiation. Supportive care is essential to prevent superimposed infection and other complications that might lead to treatment breaks or, in extreme cases, discontinuation of therapy. Technological advances with conformal radiotherapy techniques have allowed for increasing salivary gland sparing. Further protection may be achieved with existing and future medical therapies. Swallowing dysfunction following chemoradiation for laryngeal cancer is significant and may persist for 1-2 years. Efforts should be made to ensure proper patient education and reassurance in this regard.


[Quality of life after adenotonsillectomy for obstructive sleep apnea in children].
To study changes in quality of life in children after adenotonsillectomy for obstructive sleep apnea (OSA) documented by full night polysomnography. Children with OSA who fit the standard have been selected. They were asked to complete the OSA 18 quality of life survey before adenotonsillectomy and between 6 and 18 months after surgery. Scores from the preoperative and postoperative surveys were compared using the paired t test. The mean total OSA 18 score was 70.59 (SD=15.015) before surgery and 39.94 (SD=14.232) after surgery. The changes in total score, in the scores for sleep disturbance, physical symptoms, emotional symptoms, daytime functioning, and caregiver concerns, and for each item of the OSA 18 survey was highly significant (P<0.01). OSA has a relevant impact on quality of life and the children show a marked improvements after adenotonsillectomy.


Mapping four genes from human chromosome 4 to porcine chromosome 8 further develops the comparative map for an economically important chromosome of the swine genome.
Because porcine chromosome (SSC) 8 has become the focal point of many efforts aimed at identifying quantitative trait loci affecting ovulation rate, genes distributed across human chromosome (HSA) 4 were physically mapped in the pig. A more refined comparative map of this region for these two species was produced. In this study, four genes were selected based on their location in the human genome, the availability of nucleotide sequence and their genomic organization. The genes selected were fibroblast growth factor basic (FGF2; HSA 4q25-27), gonadotropin releasing hormone receptor (GNRHR; HSA 4q13), phosphodiesterase 6 B (PDE6B; HSA 4p16.3) and aminopeptidase S (PEPS; HSA 4p11-q12). Genomic libraries were screened via PCR and clones were physically assigned using fluorescence in situ hybridization (FISH). These four genes from HSA 4 were physically mapped to SSC 8p2.3 (PDE6B), 8p1.1 (PEPS), 8q1.1-1.2 (GNRHR) and 8q2.2-2.4 (FGF2). These assignments provide additional benchmarks for the comparative map and help define the level of gene order conserved between HSA 4 and SSC 8.


[Intraductal papillary-mucinous tumor of the pancreas: difficulties and mistakes of diagnostics and treatment].
15 patients with intraductal papillary-mucinous tumors (IPMT) of the pancreas were observed. Clinical manifestation corresponded with chronic pancreatitis. Ultrasound study, including endosonography, contrast-enhanced computer and magnetic resonance tomography were used in complex observation of the patients. Dilation of main or lateral pancreatic ducts, connection of tumor with pancreatic duct system and absence of septal calcinosis are typical signs in radiodiagnostics of IPMT. Visualization of parietal papillary proliferations and their contrast enhancement are undeniable signs f or neoplastic character of pancreatic duct dilation. Sensitivity of CT, MRТ and endoUS amounted accordingly 66, 83 and 88%. All patients were operated. Extent of operation was determined by morphological character, localization and size of the tumor (pylorus-preserving pancreaticoduodenal resection was carried out to 6 patients, distal resection including robot-assisted - to 7 patients, midline resection - to 1 patient, duodenum-preserving resection of head and body of pancreas - to 1 patient). Intraoperative urgent histologic study of pancreatic section was carried out by all means. Tumors with borderline degree of malignancy were detected in 4 cases.


The energetic consequences of dietary specialization in populations of the garter snake, Thamnophis elegans.
We investigated the intraspecific variation in digestive energetics between dietary specialist and generalist populations of the Western Terrestrial garter snake (Thamnophis elegans) in northern California. Coastal populations have a specialized diet of slugs and inland populations have a generalized diet of fish, anurans, mice and leeches. The difference in prey preference between the two populations is congenital, heritable and ontogenetically stable. To examine energetic specializations and trade-offs in these populations, we measured the net assimilation efficiency of each snake population on both slug (Ariolimax columbianus) and fish (Rhinichthys osculus) diets. The net assimilation efficiency was measured during digestion of a meal and continued until metabolic rate re-attained prefeeding levels. Coastal snakes were able to utilize 62% more of the ingested energy towards production from slug diets through both increased assimilation of nutrients and reduced digestive costs. For fish, assimilation and digestive costs were the same in both coastal and inland populations. These results support the hypothesis that snakes with specialized diets can evolve physiological traits to extract nutrients more efficiently. However, there was no apparent trade-off on the more generalized diet that was associated with this specialization.


Personal strengths and traumatic experiences among institutionalized children given up at birth (Les Enfants de Duplessis--Duplessis' children): I: Early experiences.
We examined childhood and early adult strengths and adverse experiences of a group of orphans given up at or near birth and raised in Quebec institutions into early adulthood. A follow-up interview of 81 adults (41 women, 40 men) at a mean age of 59.2 years included retrospective assessments of childhood experiences. Most participants reported multiple early adverse experiences, including, in descending order, unfair rules and excessive punishment, physical abuse, emotional neglect, witnessing violence, verbal abuse, physical neglect, sexual abuse, and serious illness. Adverse experiences were mainly due to lay caretakers, not peers or nuns. Twelve childhood strengths, such as self-protectiveness and athletic talent, were scored at each of four age periods, yielding a median score equivalent to one strength at each period. Over half had significant childhood attachments, but of limited intimacy. Childhood variables correlated with their respective variables in later adulthood. Overall, these older adults reported a high prevalence of adverse or traumatic childhood experiences, counterbalanced by modest levels of individual strengths and attachment relationships. Institutionalization of children--if unavoidable--must build in effective safeguards against adverse experiences.


NanoUPLC-QTOF-MS/MS Determination of Major Rosuvastatin Degradation Products Generated by Gamma Radiation in Aqueous Solution.
Rosuvastatin, a member of the statin family of drugs, is used to regulate high cholesterol levels in the human body. Moreover, rosuvastatin and other statins demonstrate a protective role against free radical-induced oxidative stress. Our research aimed to investigate the end-products of free radical-induced degradation of rosuvastatin. To induce the radical degradation, an aqueous solution of rosuvastatin was irradiated using different doses of gamma radiation (50-1000 Gy) under oxidative conditions. Rosuvastatin and related degradation products were separated on nanoC18 column under gradient elution, and identification was carried out on hyphenated nanoUPLC and nanoESI-QTOF mass spectrometer system. Elemental composition analysis using highly accurate mass measurements together with isotope fitting algorithm identified nine major degradation products. This is the first study of gamma radiation-induced degradation of rosuvastatin, where chemical structures, MS/MS fragmentation pathways and formation mechanisms of the resulting degradation products are detailly described. The presented results contribute to the understanding of the degradation pathway of rosuvastatin and possibly other statins under gamma radiation conditions.


Overview of the Knottin scorpion toxin-like peptides in scorpion venoms: Insights on their classification and evolution.
Scorpion venoms include several compounds with different pharmacological activities. Within these compounds, toxins affecting ion channels are among the most studied. They are all peptides that have been classified based on their 3D structure, chain size and function. Usually, they show a spatial arrangement characterized by the presence of a cysteine-stabilized alpha beta motif; most of them affect Na(+) and K(+) ion-channels. These features have been revised in several occasions before, but a complete phylogenetic analysis of the disulfide containing peptides is not been done. In the present contribution, two databases (Pfam and InterPro) including more than 800 toxins from different scorpions were analyzed. Pfam database included toxins from several organisms other than scorpions such as insects and plants, while InterPro included only scorpion toxins. Our results suggest that Na(+) toxins have evolved independently from those of K(+) toxins no matter the length of the peptidic chains. These preliminary results suggest that current classification needs a more detailed revision, in order to have better characterized toxin families, so the new peptides obtained from transcriptomic analyses would be properly classified.


Preparation of silica-coated poly(styrene-co-4-vinylpyridine) particles and hollow particles.
This paper presents a novel method for preparation of polymer-silica colloidal nanocomposites based on emulsion polymerization and subsequent sol-gel nanocoating process. The polystyrene latex particles bearing basic groups on their surfaces were successfully synthesized through emulsion polymerization using 4-vinylpyridine (4VP) as a functional comonomer and polyvinylpyrrolidone (PVP) as a surfactant. A series of poly(styrene-co-4-vinylpyridine)/SiO2 nanocomposite particles with smooth or rough core-shell morphology were obtained through the coating process. The poly(styrene-co-4-vinylpyridine) particles could be dissolved subsequently or simultaneously during the sol-gel coating process to form hollow particles. The effects of the amount of 4VP, PVP, NH(4)OH, and tetraethoxysilane (TEOS) on both the nanocomposite particles and hollow particles were investigated. Transmission electron microscopy showed that the morphology of the nanocomposite particles and hollow particles was strongly influenced by the initial feed of the comonomer 4VP and the coupling agent PVP. The conditions to obtain all hollow particles were also studied. Thermogravimetric analysis and energy dispersive X-ray spectroscopy analyses indicated that the interiors of hollow particles were not really "hollow".


AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings.
AutoDock Vina is arguably one of the fastest and most widely used open-source programs for molecular docking. However, compared to other programs in the AutoDock Suite, it lacks support for modeling specific features such as macrocycles or explicit water molecules. Here, we describe the implementation of this functionality in AutoDock Vina 1.2.0. Additionally, AutoDock Vina 1.2.0 supports the AutoDock4.2 scoring function, simultaneous docking of multiple ligands, and a batch mode for docking a large number of ligands. Furthermore, we implemented Python bindings to facilitate scripting and the development of docking workflows. This work is an effort toward the unification of the features of the AutoDock4 and AutoDock Vina programs. The source code is available at https://github.com/ccsb-scripps/AutoDock-Vina.


Generation of λ/12 nanowires in chalcogenide glasses.
Nanowires have been widely studied and have gained a lot of interest in the past decade. Because of their high refractive index and high nonlinearity, chalcogenide glasses (ChGs) are a good candidate for the fabrication of photonic nanowires as such nanowaveguides provide the maximal confinement of light, enabling large enhancement of nonlinear interactions and group-velocity dispersion engineering. Here we report on the generation of λ/12 (∼68 nm) nanowires based on the theoretical and experimental study of the influence of the laser repetition rate on the direct laser fabrication in ChGs (λ = 800 nm). Through a numerical model of cumulative heating, the optimum conditions for high-resolution fabrication in As(2)S(3) are found. Nanowires with dimensions down to ∼λ/12 are for the first time successfully fabricated in ChGs. We show that the generated nanowires can be stacked to form a three-dimensional woodpile photonic crystal with a pronounced stop gap.


Chromatin-associated proteins HP1 and Mod(mdg4) modify Y-linked regulatory variation in the drosophila testis.
Chromatin remodeling is crucial for gene regulation. Remodeling is often mediated through chemical modifications of the DNA template, DNA-associated proteins, and RNA-mediated processes. Y-linked regulatory variation (YRV) refers to the quantitative effects that polymorphic tracts of Y-linked chromatin exert on gene expression of X-linked and autosomal genes. Here we show that naturally occurring polymorphisms in the Drosophila melanogaster Y chromosome contribute disproportionally to gene expression variation in the testis. The variation is dependent on wild-type expression levels of mod(mdg4) as well as Su(var)205; the latter gene codes for heterochromatin protein 1 (HP1) in Drosophila. Testis-specific YRV is abolished in genotypes with heterozygous loss-of-function mutations for mod(mdg4) and Su(var)205 but not in similar experiments with JIL-1. Furthermore, the Y chromosome differentially regulates several ubiquitously expressed genes. The results highlight the requirement for wild-type dosage of Su(var)205 and mod(mdg4) in enabling naturally occurring Y-linked regulatory variation in the testis. The phenotypes that emerge in the context of wild-type levels of the HP1 and Mod(mdg4) proteins might be part of an adaptive response to the environment.


No behavioral or ERP evidence for a developmental lag in visual working memory capacity or filtering in adolescents and adults with ADHD.
Attention-deficit/hyperactivity disorder (ADHD) patients have both working memory (WM) and attention problems. Good attention skills are important for WM performance; individuals have higher WM capacity when being able to prevent storage of irrelevant information through efficient filtering. Since it is unknown how filtering ability is associated with WM performance in ADHD, this was investigated in the present study. A visuospatial working memory (VSWM) change detection task with distracting stimuli was administered to adolescents (12-16 years old) and adults (20-46 years old) with and without ADHD matched on education/IQ. Besides performance, contralateral delay activity (CDA) was measured; a neural correlate of the number of targets and distracters encoded and maintained in WM during the retention interval. Performance data showed similar WM-load, WM-distracter interference and developmental effects in ADHD and control groups. Adolescents' performance on the WM task deteriorated more than that of adults in the presence of distracters and with higher WM-load, irrespective of Diagnosis. The CDA data suggested that initially all groups encoded/maintained distracting information, but only adults were able to bounce this information from memory later in the retention interval, leading to better WM performance. The only effect of Diagnosis was a smaller CDA in adolescents and adults with ADHD than in age/IQ-matched controls when maintaining a low 1-item load, which was possibly related to an inability to keep attention focused at cued stimuli with low task demands. Overall, the development of filtering efficiency and VSWM storage capacity in adolescents with ADHD was not different from that in typically developing peers.


[Congenital dislocation of the hip treated by the Somerville technique at the age of walking. A long term review].
Sixty congenital dislocations of the hip in thirty seven children had been treated at the age of walking by the Somerville-Petit technique between 1958 and 1961. The results have been reviewed after the end of bone maturation. The results were assessed using Severin's criteria, including the Wiberg C E angle and the morphological appearances of the acetabulum and the femoral epiphysis. Nearly all the hips had at least one residual defect; less than two thirds could be described as satisfactory. The radiological study show minimal change after the age of ten. The authors conclude that the results of the technique are deceptive and they now practise, more systematically, Salter osteotomy or triple osteotomy with the expectation of better final results.


In vivo anti-inflammatory and antinociceptive effects, and in vitro antioxidant, antiglycant and anti-neuroinflammatory actions of Syzygium malaccense.
Syzygium malaccense is popularly used to treat inflammation and pain-related ailments. The species was assessed regarding its antioxidant, antiglycant, anti-inflammatory, including anti-neuroinflammatory, and antinociceptive activities. Different models were employed to measure S. malaccense extract (ESM) antioxidant activity. The antiglycant activity was determined using the glucose-induced protein glycation model. LPS-induced neuroinflammation on murine BV-2 microglial cell line was used for anti-neuroinflammatory activity evaluation. The croton oil-induced ear edema test was accomplished to evaluate the in vivo anti-inflammatory activity. Acetic acid-induced writhing together with formalin-induced paw licking assays were performed to evaluate the antinociceptive potential. Finally, the chemical characterization was accomplished by a UHPLC-MS analysis. ESM presented relevant antioxidant and antiglycant activity. NO production by BV-2 cells was reduced, indicating the relevant neuroprotective activity. ESM significantly decreased the mice ear edema induced by croton oil and the nociceptive stimulus induced by acetic acid and formalin by central and peripheral mechanisms. The flavonoids myricitrin, myricetin and quercetin were identified and, as far as we know, the alkaloid reserpine was reported in the species for the first time. The antioxidant and antiglycant potential of ESM, may be related to the in vivo anti-inflammatory and antinociceptive effects, and to the in vitro neuroinflammation inhibition.


Synergistic influence of polyoxometalate surface corona towards enhancing the antibacterial performance of tyrosine-capped Ag nanoparticles.
We illustrate a new strategy to improve the antibacterial potential of silver nanoparticles (AgNPs) by their surface modification with the surface corona of biologically active polyoxometalates (POMs). The stable POM surface corona was achieved by utilising zwitterionic tyrosine amino acid as a pH-switchable reducing and capping agent of AgNPs. The general applicability of this approach was demonstrated by developing surface coronas of phosphotungstic acid (PTA) and phosphomolybdic acid (PMA) around AgNPs. Our investigations on Gram negative bacterium Escherichia coli demonstrate that in conjugation with AgNPs, the surface corona of POMs enhances the physical damage to the bacterial cells due to synergistic antibacterial action of AgNPs and POMs, and the ability of tyrosine-reduced AgNPs (AgNPs(Y)) to act as an excellent carrier and stabiliser for the POMs. The further extension of this study towards Gram positive bacterium Staphylococcus albus showed a similar toxicity pattern, whereas these nanomaterials were found to be biocompatible for PC3 epithelial mammalian cells, suggesting the potential of these materials towards specific antimicrobial targeting for topical wound healing applications. The outcomes of this work show that facile tailorability of nanostructured surfaces may play a considerable role in controlling the biological activities of different nanomaterials.


Comparison of Helicobacter pylori stool antigen, salivary IgG, serum IgG, and serum IgM as diagnostic markers of H. pylori infection in children.
Various non-invasive diagnostic tests are available for the detection of Helicobacter pylori infection. The aim of this study was to compare the sensitivity and specificity of HpSA, salivary IgG, serum IgG, and serum IgM to those of endoscopic-biopsy as the gold standard for the diagnosis of H. pylori infection. This is a cross-sectional study performed among pediatric patients at Dr. Soetomo General Hospital (Surabaya, Indonesia). Fecal, blood, and saliva samples were collected from all subjects. The results of the HpSA, salivary IgG, serum IgG, and serum IgM tests were compared to the results of endoscopic-biopsy as the gold standard. Of the 37 study participants, H. pylori infection was confirmed in 5 (13.33%) with serum IgG, 23 (63.33%) with serum IgM, 15 (40%) with HpSA, and 26 (70.97%) with salivary IgG. The salivary IgG enzyme-linked immunosorbent assay (ELISA) was the only diagnostic test with significantly different results, as compared to biopsy (p = 0.017). The results of this study showed that HpSA, salivary IgG, and serum IgG and IgM were not sufficient to replace endoscopic-biopsy as the gold standard for the diagnosis of H. pylori infection.


Anti-titin antibodies in myasthenia gravis: tight association with thymoma and heterogeneity of nonthymoma patients.
Titin is the major autoantigen recognized by anti-striated muscle antibodies, which are characteristic of generalized myasthenia gravis (MG). To seek a correlation between anti-titin antibodies and other features of MG patients, including histopathology, age at diagnosis, anti-acetylcholine receptor (anti-AChR), autoantibody titers, and clinical severity. A novel, highly specific radioligand assay was performed on a large group of 398 patients with generalized MG. Among thymectomized patients, anti-titin antibodies were present in most patients with thymoma (56/70 [80%]), contrasting with only a minority of patients with thymus atrophy or hyperplasia (17/165 [10%]). They were also present in 64 (41%) of 155 nonthymectomized patients who had a radiologically normal thymus. In these patients and in those who had a histologically normal thymus, anti-titin antibodies were associated with a later age at onset of disease and with intermediate titers of anti-AChR antibodies. After controlling for these 2 variables, disease severity was not significantly influenced by anti-titin antibodies. Anti-titin antibodies are a sensitive marker of thymoma associated with MG in patients 60 years and younger, justifying the insistent search for a thymoma in MG patients of this age group who have these antibodies. In nonthymoma patients, anti-titin antibodies represent an interesting marker complementary to the anti-AChR antibody titer, identifying a restricted subset of patients. These clinical correlations should prompt further studies to examine the mechanisms leading to the production of anti-titin antibodies.


Double dative bond between divalent carbon(0) and uranium.
Dative bonds between p- and d-block atoms are common but species containing a double dative bond, which donate two-electron pairs to the same acceptor, are far less common. The synthesis of complexes between UCl4 and carbodiphosphoranes (CDP), which formally possess double dative bonds Cl4U⇇CDP, is reported in this paper. Single-crystal X-ray diffraction shows that the uranium-carbon distances are in the range of bond lengths for uranium-carbon double bonds. A bonding analysis suggests that the molecules are uranium-carbone complexes featuring divalent carbon(0) ligands rather than uranium-carbene species. The complexes represent rare examples with a double dative bond in f-block chemistry. Our study not only introduces the concept of double dative bonds between carbones and f-block elements but also opens an avenue for the construction of other complexes with double dative bonds, thus providing new opportunities for the applications of f-block compounds.


Indicators for the evaluation of musculoskeletal trauma systems: A scoping review and Delphi study.
Trauma is a leading cause of mortality and morbidity, disproportionately affecting low- and middle-income countries. Musculoskeletal trauma results in the majority of post-traumatic morbidity and disability globally. The literature has reported many performance indicators relating to trauma care, but few specific to musculoskeletal injuries. The purpose of this study was to establish a practical list of performance indicators to evaluate and monitor the quality and equity of musculoskeletal trauma care delivery in health systems worldwide. A scoping review was performed that identified performance indicators related to musculoskeletal trauma care. Indicators were organized by phase of care (general, prevention, pre-hospital, hospital, post-hospital) within a modified Donabedian model (structure, process, outcome, equity). A panel of 21 experts representing 45 countries was assembled to identify priority indicators utilizing a modified Delphi approach. The scoping review identified 1,206 articles and 114 underwent full text review. We included 95 articles which reported 498 unique performance indicators. Most indicators related to the hospital phase of care (n = 303, 60%) and structural characteristics (n = 221, 44%). Mortality (n = 50 articles) and presence of trauma registries (n = 16 articles) were the most frequently reported indicators. After 3 rounds of surveys our panel reached consensus on a parsimonious list of priority performance indicators. These focused on access to trauma care; processes and key resources for polytrauma triage, patient stabilization, and hemorrhage control; reduction and immobilization of fractures and dislocations; and management of compartment syndrome and open fractures. The literature has reported many performance indicators relating to trauma care, but few specific to musculoskeletal injuries. To create quality and equitable trauma systems, musculoskeletal care must be incorporated into development plans with continuous monitoring and improvement. The performance indicators identified by our expert panel and organized in a modified Donabedian model can serve as a method for evaluating musculoskeletal trauma care.


Progress in the biological synthesis of the plant cell wall: new ideas for improving biomass for bioenergy.
Lignocellulosic biomass feedstocks for biofuels are primarily the thickened secondary cells of vascular plants. Recent advances have been made in our basic understanding of how cellulose and the non-cellulosic polysaccharides of the plant cell wall are synthesized, assembled, and integrated with the synthesis of lignin. New complexities have been elucidated in the ways cellulose microfibrils are deposited at the plasma membrane surface and integrated with non-cellulosic polysaccharides are assembled and lignified into functional form. Current strategies focus on the transcriptional events that specify vascularization and fiber formation and how the composition of lignin is modified in expression variants in the natural population. This knowledge base will yield new ideas for how to enhance lignocellulosic composition and cell wall architecture in biomass tailored for its end use.


Differential Diagnosis of Endometriosis by Ultrasound: A Rising Challenge.
Ultrasound is an effective tool to detect and characterize endometriosis lesions. Variances in endometriosis lesions' appearance and distorted anatomy secondary to adhesions and fibrosis present as major difficulties during the complete sonographic evaluation of pelvic endometriosis. Currently, differential diagnosis of endometriosis to distinguish it from other diseases represents the hardest challenge and affects subsequent treatment. Several gynecological and non-gynecological conditions can mimic deep-infiltrating endometriosis. For example, abdominopelvic endometriosis may present as atypical lesions by ultrasound. Here, we present an overview of benign and malignant diseases that may resemble endometriosis of the internal genitalia, bowels, bladder, ureter, peritoneum, retroperitoneum, as well as less common locations. An accurate diagnosis of endometriosis has significant clinical impact and is important for appropriate treatment.


Study of the effect of oral health on physical condition of professional soccer players of the Football Club Barcelona.
The objective of this study was to evaluate the oral health status of professional soccer players of F.C. Barcelona and its relation to the incidence of sport lesions. Thirty professional soccer players were consecutively evaluated in the seasons 2003/4, 2004/5 and 2005/6. A research protocol to assess their oral health was developed. DMFT, Quigley & Hein plaque index (PI), Löe & Silness gingival index (GI), World Health Organization malocclusion index, Ramfjord teeth probing pocket depth (PPD), TMJ examination and history of dental trauma were recorded. All physical injuries sustained by players during the season were documented from F.C. Barcelona medical services. Mean DMFT score was 5.7 (SD 4.1), Quigley & Hein plaque index score was 2.3 (SD 1.1), Löe & Silness gingival index was 1.1 (SD 0.8), and periodontal pocket depth was 1.9 mm (SD 0.3). Pearson's analysis showed a significant correlation between PI and GI (p<0.01). Nine players (30%) presented bruxism--the same proportion of those with severe malocclusion. Seven (23.3%) players had suffered uncomplicated crown fractures. The mean incidence of physical injuries was 8 (SD 3.4) per player. PI and PPD showed a statistically significant correlation to muscle injuries (p<0.05). Soccer players, despite intensive medical follow-up, have significant oral health problems such as untreated caries, gingivitis or malocclusion, and suffer dental trauma as a result of sports activities. Their physical condition could also be associated to oral health.


Experimental evaluation of the stabilization of the COT orbitals by 4f orbitals in COT2Ce using a Hubbard model.
Significant orbital mixing is rare in lanthanide complexes because of the limited radial extent of the 4f orbitals, which results in a generally small stabilization due to 4f orbital interactions. Nevertheless, even a small amount of additional stabilization could enhance lanthanide separations. One lanthanide complex in which orbital mixing has been extensively studied both experimentally and computationally is cerocene, COT2Ce, where COT is cyclooctatetraene. This compound has a singlet ground state with a low-lying, triplet excited state. Previous fluorescence studies on trimethylsilyl-substituted cerocenes indicate the triplet state is 0.4 eV higher in energy than the singlet state. In addition, computational studies predict that the triplet is 0.3 to 1 eV higher in energy than the singlet. The synthesis of highly pure COT2Ce by Walter and Andersen allowed its physical properties to be accurately measured. Using these measurements, we evaluate the stabilization of the 4f orbitals using two, independent approaches. A Hubbard model is used to evaluate the stabilization of the ground state due to orbital mixing. This stabilization, which is also the singlet-triplet gap, is -0.29 eV using this model. This gap was also from the temperature independent paramagnetism of COT2Ce, which yielded a value of -0.32 eV.


Pseudomembranous colitis after topical application of clindamycin.
Abdominal cramping and diarrhea developed in a 24-year-old woman with facial acne vulgaris five days after she started topical therapy with 1% clindamycin hydrochloride. A stool specimen contained a significant titer of a toxin produced by Clostridium difficile. Findings from sigmoidoscopy and a colonic biopsy specimen were consistent with pseudomembranous colitis. The patient became asymptomatic after ten days of supportive care and oral vancomycin hydrochloride therapy. This case is presented as an example of pseudomembranous colitis associated with topical application of clindamycin.


High dose chemotherapy with thiotepa, mitoxantrone and carboplatin (TMJ) followed by autologous stem cell support in 100 consecutive lymphoma patients in a single centre: analysis of efficacy, toxicity and prognostic factors.
High dose chemotherapy with autologous stem cell transplant is often used in patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) who either do not respond to, or relapse after conventional chemotherapy. There is no consensus on the "ideal" pretransplant conditioning regimen. In this study, we analyzed the results of 100 consecutive patients with HD and NHL who met our eligibility criteria and underwent autologous stem cell transplant at New York Medical College and Zalmen A. Arlin Cancer Institute. All patients received high dose chemotherapy with thiotepa, mitoxantrone and carboplatin (TMJ). One hundred patients, 37 with HD and 63 with NHL underwent autologous stem cell transplant using TMJ as a conditioning regimen. All patients with HD had chemo-sensitive relapse while 50 patients with NHL had chemo-sensitive relapse and 13 patients had first complete remission. The source of stem cells was bone marrow (18 patients), peripheral blood (50 patients) and both bone marrow and peripheral blood (32 patients). With a median follow up of 91 months (range 23-147 months), the median survival of patients with HD and NHL who underwent autologous stem cell transplant is 107 months and the 5 years disease free survival is 43%. Median survival of patients with HD and NHL is 87 and 107 months respectively. There were 4 transplant related deaths. Median survival of patients who had sensitive relapse at the time of transplant is 87 months while median survival has not been reached for patients who had first complete remission at the time of transplant. Multivariate analysis identified age>35 years (P=0.02) as a predictor for poor survival for the whole group as well as for patients with NHL (P=0.04). TMJ is a safe and effective regimen when used as a part of autologous stem cell transplant for patients with HD and NHL.


Mitochondrial genome sequencing helps show the evolutionary mechanism of mitochondrial genome formation in Brassica.
Angiosperm mitochondrial genomes are more complex than those of other organisms. Analyses of the mitochondrial genome sequences of at least 11 angiosperm species have showed several common properties; these cannot easily explain, however, how the diverse mitotypes evolved within each genus or species. We analyzed the evolutionary relationships of Brassica mitotypes by sequencing. We sequenced the mitotypes of cam (Brassica rapa), ole (B. oleracea), jun (B. juncea), and car (B. carinata) and analyzed them together with two previously sequenced mitotypes of B. napus (pol and nap). The sizes of whole single circular genomes of cam, jun, ole, and car are 219,747 bp, 219,766 bp, 360,271 bp, and 232,241 bp, respectively. The mitochondrial genome of ole is largest as a resulting of the duplication of a 141.8 kb segment. The jun mitotype is the result of an inherited cam mitotype, and pol is also derived from the cam mitotype with evolutionary modifications. Genes with known functions are conserved in all mitotypes, but clear variation in open reading frames (ORFs) with unknown functions among the six mitotypes was observed. Sequence relationship analysis showed that there has been genome compaction and inheritance in the course of Brassica mitotype evolution. We have sequenced four Brassica mitotypes, compared six Brassica mitotypes and suggested a mechanism for mitochondrial genome formation in Brassica, including evolutionary events such as inheritance, duplication, rearrangement, genome compaction, and mutation.


THIS ARTICLE HAS BEEN RETRACTED. Physical therapy for premature ejaculation, erectile dysfunction and chronic pelvic pain syndrome.
There is limited knowledge about the exact role of the pelvic floor in male sexual functioning. Pelvic floor muscle function might be involved in the enhancement of blood flow to the penis, and evidence suggests an active role for the ischio- and bulbocavernous muscles and other pelvic floor muscles in the initiation and maintenance of erection. Increased activity of pelvic floor muscles might also be preparatory to ejaculation. Studies have shown positive results after physical therapy for erectile dysfunction, premature ejaculation and chronic pelvic pain syndrome. However, the methodological quality of some of these studies is poor and further research validating specific physical therapies in the assessment and treatment of male sexual function is necessary. In this respect physical therapists have a potential role as integral members of healthcare teams involved in the improvement of male sexual health.


Effect of Incorporated ZnO Nanoparticles on the Corrosion Performance of SiO2 Nanoparticle-Based Mechanically Robust Epoxy Coatings.
This paper presents the studies of the development of a high-performance epoxy coating for steel substrates. To this end, it investigated the synergistic effect of incorporating zinc oxide (ZnO) nanoparticles into nanosilica containing epoxy formulations. The mechanical properties of the epoxy coating formulations were improved by modifying the surfaces of the silica nanoparticles (5 wt.%) with 3-glycidoxypropyl trimethoxysilane, which ensured their dispersal through the material. Next, the ZnO nanoparticles (1, 2, or 3 wt.%) were incorporated to improve the corrosion performance of the formulations. The anticorrosive properties of the coatings were examined by electrochemical impedance spectroscopy (EIS) of coated mild steel specimens immersed in 3.5% NaCl solution over different time intervals (1 h to 30 days). Incorporation of the ZnO nanoparticles and the nanosilica into the coating formulation improved the corrosion resistance of the epoxy coating even after long-term exposure to saline test solutions. Finally, to evaluate how the nanoparticles affected the chemical and morphological properties of the prepared coatings, the coatings were characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD).


An europium(III) diglycolamide complex: insights into the coordination chemistry of lanthanides in solvent extraction.
The synthesis, stoichiometry, and structural characterization of a homoleptic, cationic europium(III) complex with three neutral tetraalkyldiglycolamide ligands are reported. The tri(bismuth tetrachloride)tris(N,N,N',N'-tetra-n-octyldiglycolamide)Eu salt, [Eu(TODGA)3][(BiCl4)3] obtained from methanol was examined by Eu L3-edge X-ray absorption spectroscopy (XAS) to reveal an inner-sphere coordination of Eu(3+) that arises from 9 O atoms and two next-nearest coordination spheres that arise from 6 carbon atoms each. A structural model is proposed in which each TODGA ligand with its O=Ca-Cb-O-Cb-Ca=O backbone acts as a tridentate O donor, where the two carbonyl O atoms and the one ether O atom bond to Eu(3+). Given the structural rigidity of the tridentate coordination motif in [Eu(TODGA)3](3+) with six 5-membered chelate rings, the six Eu-Ca and six Eu-Cb interactions are readily resolved in the EXAFS (extended X-ray absorption fine structure) spectrum. The three charge balancing [BiCl4](-) anions are beyond the cationic [Eu(TODGA)3](3+) cluster in an outer sphere environment that is too distant to be detected by XAS. Despite their sizeable length and propensity for entanglement, the four n-octyl groups of each TODGA (for a total of twelve) do not perturb the Eu(3+) coordination environment over that seen from previously reported single-crystal structures of tripositive lanthanide (Ln(3+)) complexes with tetraalkyldiglycolamide ligands (of the same 1:3 metal-to-ligand ratio stoichiometry) but having shorter i-propyl and i-butyl groups. The present results set the foundation for understanding advanced solvent extraction processes for the separation of the minor, tripositive actinides (Am, Cm) from the Ln(3+) ions in terms of the local structure of Eu(3+) in a solid state coordination complex with TODGA.


Association between conversion to in-center nocturnal hemodialysis and right ventricular remodeling.
In-center nocturnal hemodialysis (INHD) is associated with favorable left ventricular (LV) remodeling. Although right ventricular (RV) structure and function carry prognostic significance, the impact of dialysis intensification on RV is unknown. Our objectives were to evaluate changes in RV mass index (MI), end-diastolic volume index (EDVI), end-systolic volume index (ESVI) and ejection fraction (EF) after conversion to INHD and their relationship with LV remodeling. Of 67 conventional hemodialysis (CHD, 4 h/session, three times/week) patients, 30 continued on CHD and 37 converted to INHD (7-8 h/session, three times/week). Cardiac magnetic resonance imaging was performed at baseline and 1 year using a standardized protocol; an experienced and blinded reader performed RV measurements. At 1 year there were significant reductions in RVMI {-2.1 g/m2 [95% confidence interval (CI) -3.8 to - 0.4], P = 0.017}, RVEDVI [-9.5 mL/m2 (95% CI - 16.3 to - 2.6), P = 0.008] and RVESVI [-6.2 mL/m2 (95% CI - 10.9 to - 1.6), P = 0.011] in the INHD group; no significant changes were observed in the CHD group. Between-group comparisons showed significantly greater reduction of RVESVI [-7.9 mL/m2 (95% CI - 14.9 to - 0.9), P = 0.03] in the INHD group, a nonsignificant trend toward greater reduction in RVEDVI and no significant difference in RVMI and RVEF changes. There was significant correlation between LV and RV in terms of changes in mass index (MI) (r = 0.46), EDVI (r = 0.73), ESVI (r = 0.7) and EF (r = 0.38) over 1 year (all P < 0.01). Conversion to INHD was associated with a significant reduction of RVESVI. Temporal changes in RV mass, volume and function paralleled those of LV. Our findings support the need for larger, longer-term studies to confirm favorable RV remodeling and determine its impact on clinical outcomes.


The short lived suppressor cell assay and its relationship with mitogen responsiveness in normal individuals.
The short lived suppressor cell(SLSC) assay is an indirect test for spontaneous suppressor cell activity based on the principle that some suppressor cells are short lived in culture. It measures the ratio (suppressor index) between 3H-thymidine incorporation by lymphocytes stimulated by concanavalin-A (Con-A) after 24 hours of preincubation (during which SLSC are lost) to that incorporated by cultures stimulated immediately (SLSC present). In autoimmune conditions decreased suppressor indices are reported but low responses to mitogen stimulation also occur. The aim of this study was to investigate whether low levels of mitogen responsiveness could lead per se to low suppressor indices. A simultaneous analysis of suppressor indices and mitogen responses to Con-A, PHA and PWM of peripheral blood mononuclear cells in normal individuals was performed. There was an inverse correlation between responses to Con-A or PHA and the suppressor indices, indicating that low mitogen responsiveness does not lead per se to decreased SLSC activity and furthermore that the activity of SLSC may modulate lymphocyte reactivity in vitro.


[Twin-to-twin transfusion syndrome--case report].
Authors described a case of twin-to-twin transfusion syndrome that did not comply with a classic definition of syndrome. It has been presented possibilities of ultrasound screening regarding to Doppler blood flow velocimetry. It has been also shown the usefulness of these methods in the monitoring and assessment of fetal status. This is an example of Doppler blood flow velocimetry applying that yields information concerning fetal condition. This method seems to be very useful in these situations when fetal heart rate monitoring is difficult or even inapplicable.


The aortic root in repaired tetralogy of Fallot: Serial measurements and impact of losartan treatment.
Aortic root dilatation is common in adults with repaired tetralogy of Fallot (rTOF) and might lead to aortic dissection. However, little is known on progression of aortic dilatation and the effect of pharmaceutical treatment. This study aims to determine factors associated with aortic growth and investigate effects of losartan. We performed a prespecified analysis from the 1:1 randomized, double-blind REDEFINE trial. Aortic root diameters were measured at baseline and after 2.0 ± 0.3 years of follow-up using cardiovascular magnetic resonance (CMR) imaging. A total of 66 patients were included (68% men, age 40 ± 12 years, baseline aortic root 37 ± 6 mm, 32% aortic dilatation (>40 mm)). There was a trend towards slow aortic root growth (+0.6 ± 2.3 mm after two years, p = 0.06) (n = 60). LV stroke volume was the only factor associated with both a larger baseline aortic root (β: 0.09 mm/ml (95% C.I.:0.02, 0.15), p = 0.010) and with aortic growth during follow-up (β: 0.04 mm/ml (95% C.I.:0.005, 0.066), p = 0.024), after correction for age, sex, and body surface area using linear regression analysis. No treatment effect of losartan was found (p = 0.17). Aortic root dilatation was present in about one-third of rTOF patients. A larger LV stroke volume was associated with both a larger baseline aortic root and ongoing growth. Our findings provide no arguments for lower aortic diameter thresholds for prophylactic surgery compared to the general population.


Equine colitis X associated with infection by Clostridium difficile NAP1/027.
A 14-year-old Quarter Horse with a 48-hr history of colic was euthanized after failure to respond to treatment. At necropsy, cecal and colonic mucosae were congested throughout, and there was segmental edema and significant thickening of the intestinal wall. Excessive numbers of mononuclear cells were found in mucosal lamina propria. Submucosal hemorrhage was diffuse and extensive, and Clostridium difficile toxins A and B were detected. Large numbers of C. difficile were isolated, and genetic characterization revealed them to be North American pulsed-field gel electrophoresis type 1, polymerase chain reaction ribotype 027, and toxinotype III. Genes for the binary toxin were present, and toxin negative-regulator tcdC contained an 18-bp deletion. This genotype comprises the current human "epidemic strain," which is associated with human C. difficile-associated disease of greater than historical severity. The diagnosis was peracute typhlocolitis, with lesions and history typical of those attributed to colitis X.


Non-syndromal multiple supernumerary and permanent impacted teeth in mother and her one child.
Multiple permanent impacted supernumerary teeth are rare and are most of the times associated with syndromes. The prevalence for non-syndromic multiple supernumerary teeth is less than 1%. We herein presenting a case of non-syndromic multiple supernumerary impacted teeth in a female patient and her child. The patient has three children; out of them, two had normal dentition and the youngest child had 60 teeth (35 impacted supernumerary with 25 erupted teeth). The patient herself had a total of 54 teeth. Their medical history was not significant. The systemic investigations were not suggestive of any syndrome and disease. Very few cases reported more than 30 supernumerary and impacted teeth bilaterally in both the jaws. This case report becomes unique as both mother and her child presented with more than 30 supernumerary impacted teeth.


Skin Temperature Over the Carotid Artery, an Accurate Non-invasive Estimation of Near Core Temperature.
During anesthesia, continuous body temperature monitoring is essential, especially in children. Anesthesia can increase the risk of loss of body temperature by three to four times. Hypothermia in children results in increased morbidity and mortality. Since the measurement points of the core body temperature are not easily accessible, near core sites, like rectum, are used. The purpose of this study was to measure skin temperature over the carotid artery and compare it with the rectum temperature, in order to propose a model for accurate estimation of near core body temperature. Totally, 124 patients within the age range of 2 - 6 years, undergoing elective surgery, were selected. Temperature of rectum and skin over the carotid artery was measured. Then, the patients were randomly divided into two groups (each including 62 subjects), namely modeling (MG) and validation groups (VG). First, in the modeling group, the average temperature of the rectum and skin over the carotid artery were measured separately. The appropriate model was determined, according to the significance of the model's coefficients. The obtained model was used to predict the rectum temperature in the second group (VG group). Correlation of the predicted values with the real values (the measured rectum temperature) in the second group was investigated. Also, the difference in the average values of these two groups was examined in terms of significance. In the modeling group, the average rectum and carotid temperatures were 36.47 ± 0.54°C and 35.45 ± 0.62°C, respectively. The final model was obtained, as follows: Carotid temperature × 0.561 + 16.583 = Rectum temperature. The predicted value was calculated based on the regression model and then compared with the measured rectum value, which showed no significant difference (P = 0.361). The present study was the first research, in which rectum temperature was compared with that of skin over carotid artery, to find a safe location with easier access and higher accuracy for estimating near core body temperature. Results obtained in this study showed that, using a model, it is possible to evaluate near core body temperature in children, by measuring skin temperature over carotid artery.


Identification of ALV-J associated acutely transforming virus Fu-J carrying complete v-fps oncogene.
Transduction of oncogenes by ALVs and generation of acute transforming viruses is common in natural viral infections. In order to understand the molecular basis for the rapid oncogenicity of Fu-J, an acutely transforming avian leukosis virus isolated from fibrosarcomas in crossbreed broilers infected with subgroup J avian leukosis virus (ALV-J) in China, complete genomic structure of Fu-J virus was determined by PCR amplification and compared with those of Fu-J1, Fu-J2, Fu-J3, Fu-J4, and Fu-J5 reported previously. The results showed that the genome of Fu-J was defective, with parts of gag gene replaced by the complete v-fps oncogene and encoded a 137 kDa Gag-fps fusion protein. Sequence analysis revealed that Fu-J and Fu-J1 to Fu-J5 were related quasi-species variants carrying different lengths of v-fps oncogenes generated from recombination between helper virus and c-fps gene. Comparison of virus carrying v-fps oncogene also gave us a glimpse of the molecular characterization and evolution process of the acutely transforming ALV.


Decreased Sound Tolerance in Tinnitus Patients.
(1) Background: Decreased sound tolerance is a significant problem in tinnitus sufferers. The aim of the study was to evaluate the relationship between tinnitus and decreased sound tolerance (hyperacusis and misophonia). (2) Methods: The study sample consisted of 74 patients with tinnitus and decreased sound tolerance. The procedure comprised patient interviews, pure tone audiometry, impedance audiometry, measurement of uncomfortable loudness levels, and administration of the Hyperacusis Questionnaire, Tinnitus Handicap Inventory, and Visual Analogue Scales. (3) Results: The majority (69%) of the patients reported that noise aggravated their tinnitus. The correlation between tinnitus and hyperacusis was found to be statistically significant and positive: r = 0.44; p < 0.01. The higher the tinnitus severity, the greater the hyperacusis. There was no correlation between misophonia and hyperacusis (r = 0.18; p > 0.05), or between misophonia and tinnitus (r = 0.06; p > 0.05). (4) Conclusions: For tinnitus patients the more significant problem was hyperacusis rather than misophonia. The diagnosis and treatment of decreased sound tolerance should take into account not only audiological, but also psychological problems of the patients.


Role of protein kinase C in control of ethanol-modulated beta-endorphin release from hypothalamic neurons in primary cultures.
We have previously shown that short-term exposure to ethanol stimulates immunoreactive beta-endorphin (IR-beta-EP) release from hypothalamic neurons and that chronic ethanol exposure decreases the IR-beta-EP release from these neurons. The role of protein kinase C (PKC) in the ethanol-regulated beta-EP release from hypothalamic neurons has not been established. In this study, by using the primary cultures of hypothalamic neurons, we tested the effects of PKC stimulator phorbol ester 4 beta-phorbol 12-myristate-13-acetate (PMA) and PKC inhibitor chelerythrine chloride on ethanol-induced IR-beta-EP release. Additionally, the effects of ethanol with or without PMA on expression and translocation of various PKC isoenzymes from cytosolic to membrane fraction were determined. PMA treatment increased IR-beta-EP release in a time- and dose-dependent manner. Acute ethanol treatment (3 h) increased, while chronic ethanol treatment (24 h) reduced, the magnitude of PMA-induced IR-beta-EP release. The stimulatory effect of acute ethanol on IR-beta-EP release was reduced by chelerythrine chloride. Determination of the effects of ethanol with or without PMA on seven different PKC isoenzymes (PKC-alpha, -beta I, -beta II, -gamma, -delta, -epsilon, and -zeta) revealed that the expression and translocation of only two PKC isoenzymes, PKC-delta and PKC-epsilon, were stimulated by acute treatment with ethanol. Acute ethanol also increased PMA-stimulated expression of these two isoenzymes. Chronic ethanol treatment reduced both basal and PMA-induced increase of PKC-delta and PKC-epsilon expression and translocation. These data provide evidence for the first time that ethanol-regulated IR-beta-EP secretion is controlled by the PKC system, possibly involving PKC-delta and PKC-epsilon isoenzymes.


DNMT inhibitors reverse a specific signature of aberrant promoter DNA methylation and associated gene silencing in AML.
Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are neoplastic disorders of hematopoietic stem cells. DNA methyltransferase inhibitors, 5-azacytidine and 5-aza-2'-deoxycytidine (decitabine), benefit some MDS/AML patients. However, the role of DNA methyltransferase inhibitor-induced DNA hypomethylation in regulation of gene expression in AML is unclear. We compared the effects of 5-azacytidine on DNA methylation and gene expression using whole-genome single-nucleotide bisulfite-sequencing and RNA-sequencing in OCI-AML3 cells. For data analysis, we used an approach recently developed for discovery of differential patterns of DNA methylation associated with changes in gene expression, that is tailored to single-nucleotide bisulfite-sequencing data (Washington University Interpolated Methylation Signatures). Using this approach, we find that a subset of genes upregulated by 5-azacytidine are characterized by 5-azacytidine-induced signature methylation loss flanking the transcription start site. Many of these genes show increased methylation and decreased expression in OCI-AML3 cells compared to normal hematopoietic stem and progenitor cells. Moreover, these genes are preferentially upregulated by decitabine in human primary AML blasts, and control cell proliferation, death, and development. Our approach identifies a set of genes whose methylation and silencing in AML is reversed by DNA methyltransferase inhibitors. These genes are good candidates for direct regulation by DNA methyltransferase inhibitors, and their reactivation by DNA methyltransferase inhibitors may contribute to therapeutic activity.


Curcumin Interacts with α-Synuclein Condensates To Inhibit Amyloid Aggregation under Phase Separation.
The amyloid aggregation of α-synuclein (α-Syn) is highly associated with Parkinson's disease (PD). Discovering α-Syn amyloid inhibitors is one of the strategies for PD therapies. Recent studies suggested that α-Syn undergoes phase separation to accelerate amyloid aggregation. Molecules modulating α-Syn phase separation or transition have the potential to regulate amyloid aggregation. Here, we discovered that curcumin, a small natural molecule, interacts with α-Syn during phase separation. Our study showed that curcumin neither affects the formation of α-Syn condensates nor influences the initial morphology of α-Syn condensates. However, curcumin decreases the fluidity of α-Syn inside the condensates and efficiently inhibits α-Syn from turning into an amyloid. It also inhibits the amyloid aggregations of PD disease-related α-Syn E46K and H50Q mutants under phase separation. Furthermore, curcumin can destabilize preformed α-Syn amyloid aggregates in the condensates. Together, our findings demonstrate that curcumin regulates α-Syn amyloid formation during protein phase separation and reveal that α-Syn amyloid aggregation under phase separation can be modulated by small molecules.


A comparative study of the second-order hydrophobic moments for globular proteins: the consensus scale of hydrophobicity and the CHARMM partial atomic charges.
In this paper, the second-order hydrophobic moment for fifteen globular proteins in 150 nonhomologous protein chains was performed in a comparative study involving two sets of hydrophobicity: one selected from the consensus scale and the other derived from the CHARMM partial atomic charges. These proteins were divided into three groups, based on their number of residues (N) and the asphericity (δ). Proteins in Group I were spherical and those in Groups II and III were prolate. The size of the proteins is represented by the mean radius of gyration (R(g) ), which follows the Flory scaling law, R(g) ∝ N(ν). The mean value of v was 0.35, which is similar to a polymer chain in a poor solvent. The spatial distributions of the second-order moment for each of the proteins, obtained from the two sets of hydrophobicity, were compared using the Pearson correlation coefficient; the results reveal that there is a strong correlation between the two data sets for each protein structure when the CHARMM partial atomic charges, |q(i)| ≥ 0.3, assigned for polar atoms, are used. The locations at which these distributions vanish and approach a negative value are at approximately 50% of the percentage of solvent accessibility, indicating that there is a transition point from hydrophobic interior to hydrophilic exterior in the proteins. This may suggest that there is a position for the proteins to determine the residues at exposed sites beyond this range.