Lipid peroxidation in peribacteroid membranes from French-bean nodules.
Enriched peribacteroid membranes were prepared from Phaseolus vulgaris nodules and, in the presence of metleghemoglobin and H(2)O(2), membranal lipid peroxidation was observed. The initial rate of the reaction was low and increased with time. Ferrous leghemoglobin was unable to induce this peroxidation with H(2)O(2). Thus, it appears that leghemoglobin (IV) is not the activated species involved in this process. Heme plays a role in this peroxidation and the hydroxyl radical is not an intermediate of the reaction. Lipid peroxidation in peribacteroid membranes was also observed in the presence of iron ions. A mixture of iron (III) and iron (II) produced a maximal peroxidation. Senescing nodule extracts were able to provoke membranal lipid peroxidation; they contained nonprotein-bound iron. Peribacteroid membranes were more sensitive than microsomes to peroxidation, as measured by malonaldehyde formation.


Status of the Medicaid competition demonstrations.
In 1982, the Health Care Financing Administration approved funding for demonstration programs in six States to test a variety of alternative delivery strategies for Medicaid recipients. A number of innovative health service delivery features have been used in these programs, including competition, capitation, case management, and limitations on provider choice. These strategies have been tried in order to address the key Medicaid problems of cost containment and access to appropriate and high quality care. This article provides an overview of how the demonstration sites have approached the task of designing, developing, and implementing their various programs.


Betainium trifluoroacetate.
The title compound, C5H12NO2+*C2F3O2- or BET+*CF3COO- [BET is trimethylglycine (betaine); IUPAC: 1-carboxy-N,N,N-trimethylmethanaminium inner salt], contains pairs of betainium and trifluoroacetate ions forming a dimer bridged by a strong hydrogen bond between the carboxyl and carboxylate groups of the two ions. The molecular symmetry of the cation is close to Cs, with protonation occurring at the carboxy O atom positioned anti to the N atom. The trifluoroacetate anions are disordered over two positions. In one, the conformation of the CF3 group is staggered with respect to the carboxylate group, in the other, it is close to an eclipsed conformation. The sole hydrogen bond present in the structure is the strong O-H...O bond between the anion and the cation.


A Miniature Optical Force Dual-Axis Accelerometer Based on Laser Diodes and Small Particles Cavities.
In recent years, the optical accelerometer based on the optical trapping force effect has gradually attracted the attention of researchers for its high sensitivity and high measurement accuracy. However, due to its large size and the complexity of optical path adjustment, the optical force accelerometers reported are only suitable for the laboratory environment up to now. In this paper, a miniature optical force dual-axis accelerometer based on the miniature optical system and a particles cavity which is prepared by Micro-Electro-Mechanical Systems (MEMS) technology is proposed. The overall system of the miniature optical levitation including the miniature optical system and MEMS particles cavity is a cylindrical structure with a diameter of about 10 mm and a height of 33 mm (Φ 10 mm × 33 mm). Moreover, the size of this accelerometer is 200 mm × 100 mm × 100 mm. Due to the selected light source being a laser diode light source with elliptical distribution, it is sensitive to the external acceleration in both the long axis and the short axis. This accelerometer achieves a measurement range of ±0.17 g-±0.26 g and measurement resolution of 0.49 mg and 1.88 mg. The result shows that the short-term zero-bias stability of the two orthogonal axes of the optical force accelerometer is 4.4 mg and 9.2 mg, respectively. The main conclusion that can be drawn is that this optical force accelerometer could provide an effective solution for measuring acceleration with an optical force effect for compact engineering devices.


The Use and Concurrent Use of Side Effect Controlling Medications Among Women on Aromatase Inhibitors.
Background: Women on aromatase inhibitors (AIs) as part of their breast cancer treatment often experience difficult to control side effects. Although there are several medications to manage the side effects of AI therapy, many of them are associated with their own risk, particularly sedation. The objective of this study was to describe the prescribing practices for side effect managing (SE) medications among women with breast cancer on AI therapy and to assess for combinations of medications that may present a clinical risk to patients. Methods: Retrospective data analysis using Surveillance, Epidemiology and End Results (SEER)-Medicare data of all women aged 66-90 years with stage I-III hormone positive breast cancer diagnosed between 2008 and 2014 who initiated AI therapy within 12 months of their diagnosis. We determined the percentage of patients prescribed an SE medication in the 12 months prior and in the 24 months after the initiation of AI therapy. We calculated the number of prescriptions and the number of days of overlapping (i.e., >1 SE) prescriptions, and examined predictors of overlapping prescriptions. Results: The use of SE medications was pervasive and increased after initiation of AI therapy. The most commonly prescribed medications were opiates (55.1%), selective serotonin reuptake inhibitors (22.6%), benzodiazepines (18.4%), tramadol (17.7%) and gabapentin (14.6%). In total 15.5% of patients had overlapping prescriptions; among those, 36.2% had three overlapping prescriptions. Prior use was the strongest predictor of overlapping prescriptions with an odds ratio of 7.9 (95% confidence interval: 7.17-8.77). Conclusion: Among women on AI therapy, the use of SE medications is common and many have overlapping prescriptions raising concern for potential harm from polypharmacy.


Oral lesions in children born to HIV-1 positive women.
A cohort of 69 children born to HIV-1 positive women was studied to evaluate types, prevalences and relationships to clinical stages of HIV-1-related oral lesions. In addition, relationships among C. albicans biotypes, clinical features of oral candidiasis and HIV-1 disease were investigated. C. albicans biotypes did not correlate with clinical features of oral lesions, disease stages and CD4+ lymphocyte count. Of 8 patients with recurrent oral candidiasis, 4 changed clinical features and 5 changed biotype. Our study pointed out the high frequency (28.9%) of oral lesions, especially caused by fungi and the importance of the examination of the oral cavity in children born to HIV-1 positive women.


Pieter Cullis' quest for a lipid-based, fusogenic delivery system for nucleic acid therapeutics: success with siRNA so what about mRNA?
For the best part of 40 years, lipids and membrane fusion have been at the center of Pieter's research. Projects range from the purely academic quest of understanding the roles of lipids in biological membranes, to the translation of this knowledge into the most advanced lipid nanoparticle (LNP) drug delivery systems in clinical trials to-date. Pieter's pioneering work in lipid polymorphism and characterizing the unique properties of unsaturated phospatidyethanolamines (PE), together with the introduction of ionizable, dialkylamino lipids to trigger membrane fusion at acidic pH, provided the foundation on which a new generation of highly potent, well-tolerated LNPs for intravenous delivery of nucleic acid therapeutics has been built. In this contribution to the special edition honoring Pieter's achievements we highlight key research conducted in Pieter's laboratory and at several biotechnology companies, some spun out of his research group, which resulted in the development of a fusogenic delivery system for siRNA therapeutics. Patisiran®, an LNP encapsulating siRNA for hepatic gene silencing, is currently in Phase III clinical trials for treatment of Transthyretin amyloidosis as are several other siRNA products employing this delivery technology. Finally, we describe more recent work in which the platform shows real promise in the rapidly growing new field of mRNA therapeutics.


Quantitative chemical shift imaging of vertebral bone marrow in patients with Gaucher disease.
To evaluate extent of bone marrow involvement and disease severity in Gaucher patients, results of modified Dixon quantitative chemical shift imaging (QCSI) of the lumbar spine were correlated with quantitative analysis of marrow triglycerides and glucocerebrosides and with quantitative determination of splenic volume at magnetic resonance (MR) imaging. High-field-strength MR spectra of surgical marrow specimens were dominated by a single fat and a water peak, validating use of QCSI. QCSI showed average vertebral marrow fat fractions of 10% +/- 8 in Gaucher patients (normal adult averages, 29% +/- 6). Relaxation times for lipid and water approximated normal averages; bulk T1 values were significantly longer, reflecting decreased marrow fat. Glucocerebroside concentrations were higher in Gaucher marrow and inversely correlated with triglyceride concentrations. Extent of marrow infiltration determined by fat fraction measurements correlated with disease severity measured by splenic enlargement. These results show that as Gaucher cells infiltrate bone marrow and displace normal marrow adipocytes, bulk T1 increases due to the higher T1 of water compared with that of fat. QCSI provides a sensitive, noninvasive technique for evaluating bone marrow involvement in Gaucher disease.


Generation of vector beams with arbitrary spatial variation of phase and linear polarization using plasmonic metasurfaces.
A novel method is proposed to generate vector beams with arbitrary spatial variation of phase and linear polarization at the nanoscale using compact plasmonic metasurfaces with rectangular nanoapertures. The physical mechanism underlying the simultaneous control of light polarization and phase is explained. Vector beams with different spiral phasefronts are obtained by manipulating the local orientation and geometric parameters of the metasurfaces. In addition, radially and azimuthally polarized vector beams and double-mode vector beams are achieved through completely compensating for the Berry phase, which provides additional degrees of freedom for beam manipulation.


Design and characterization of cellular automata based associative memory for pattern recognition.
This paper reports a cellular automata (CA) based model of associative memory. The model has been evolved around a special class of CA referred to as generalized multiple attractor cellular automata (GMACA). The GMACA based associative memory is designed to address the problem of pattern recognition. Its storage capacity is found to be better than that of Hopfield network. The GMACA are configured with nonlinear CA rules that are evolved through genetic algorithm (GA). Successive generations of GA select the rules at the edge of chaos. The study confirms the potential of GMACA to perform complex computations like pattern recognition at the edge of chaos.


Hitherto unknown [Fe-Fe]-hydrogenase gene diversity in anaerobes and anoxic enrichments from a moderately acidic fen.
Newly designed primers for [Fe-Fe]-hydrogenases indicated that (i) fermenters, acetogens, and undefined species in a fen harbor hitherto unknown hydrogenases and (ii) Clostridium- and Thermosinus-related primary fermenters, as well as secondary fermenters related to sulfate or iron reducers might be responsible for hydrogen production in the fen. Comparative analysis of [Fe-Fe]-hydrogenase and 16S rRNA gene-based phylogenies indicated the presence of homologous multiple hydrogenases per organism and inconsistencies between 16S rRNA gene- and [Fe-Fe]-hydrogenase-based phylogenies, necessitating appropriate qualification of [Fe-Fe]-hydrogenase gene data for diversity analyses.


Metabolism of the Neonicotinoid insecticides acetamiprid and thiacloprid by the yeast Rhodotorula mucilaginosa strain IM-2.
A yeast identified as Rhodotorula mucilaginosa strain IM-2 was able to degrade acetamiprid (AAP) and thiacloprid (THI) in sucrose mineral salt medium with half-lives of 3.7 and 14.8 days, respectively, while it did not degrade imidacloprid and imidaclothiz. Identification of metabolites indicated that R. mucilaginosa IM-2 selectively converted AAP and THI by hydrolysis of AAP to form an intermediate metabolite IM 1-3 and hydrolysis of THI to form an amide derivative, respectively. Metabolite IM 1-3 had no insecticidal activity, while the THI amide showed considerable insecticidal activity but was 15.6 and 38.6 times lower than the parent THI following oral ingestion and a contact test against the horsebean aphid Aphis craccivora , respectively. The inoculated R. mucilaginosa IM-2 displayed biodegradability of AAP and THI in clay soils.


RNA-binding protein Muscleblind-like 3 (MBNL3) disrupts myocyte enhancer factor 2 (Mef2) {beta}-exon splicing.
Mammalian MBNL (muscleblind-like) proteins are regulators of alternative splicing and have been implicated in myotonic dystrophy, the most common form of adult onset muscular dystrophy. MBNL3 functions as an inhibitor of muscle differentiation and is expressed in proliferating muscle precursor cells but not in differentiated skeletal muscle. Here we demonstrate that MBNL3 regulates the splicing pattern of the muscle transcription factor myocyte enhancer factor 2 (Mef2) by promoting exclusion of the alternatively spliced β-exon. Expression of the transcriptionally more active (+)β isoform of Mef2D was sufficient to overcome the inhibitory effects of MBNL3 on muscle differentiation. These data suggest that MBNL3 antagonizes muscle differentiation by disrupting Mef2 β-exon splicing. MBNL3 regulates Mef2D splicing by directly binding to intron 7 downstream of the alternatively spliced exon in the pre-mRNA. The RNA binding activity of MBNL3 requires the CX(7)CX(4-6)CX(3)H zinc finger domains. Using a cell culture model of myotonic dystrophy and myotonic dystrophy patient tissue, we have evidence that expression of CUG expanded RNAs can lead to an increase in MBNL3 expression and a decrease in Mef2D β-exon splicing. These studies suggest that elevating MBNL3 activity in myogenic cells could lead to muscle degeneration disorders such as myotonic dystrophy.


The Middle-East connection of Wolman Disease.
The clinical, laboratory and cytological features of 2 Bahraini infants with Wolman's disease are described. While one of the cases showed the classical diagnostic features, the other case exhibited a few atypical features such as lack of adrenal calcification and unusual morphology of vacuolated marrow macrophages. Literature review shows that this disorder may not be rare in this region.


Response to neoadjuvant chemotherapy and survival in molecular subtypes of resectable gastric cancer: a post hoc analysis of the D1/D2 and CRITICS trials.
Epstein-Barr virus positivity (EBV+) and microsatellite instability (MSI-high) are positive prognostic factors for survival in resectable gastric cancer (GC). However, benefit of perioperative treatment in patients with MSI-high tumors remains topic of discussion. Here, we present the clinicopathological outcomes of patients with EBV+, MSI-high, and EBV-/MSS GCs who received either surgery only or perioperative treatment. EBV and MSI status were determined on tumor samples collected from 447 patients treated with surgery only in the D1/D2 trial, and from 451 patients treated perioperatively in the CRITICS trial. Results were correlated to histopathological response, morphological tumor characteristics, and survival. In the D1/D2 trial, 5-year cancer-related survival was 65.2% in 47 patients with EBV+, 56.7% in 47 patients with MSI-high, and 47.6% in 353 patients with EBV-/MSS tumors. In the CRITICS trial, 5-year cancer-related survival was 69.8% in 25 patients with EBV+, 51.7% in 27 patients with MSI-high, and 38.6% in 402 patients with EBV-/MSS tumors. Interestingly, all three MSI-high tumors with moderate to complete histopathological response (3/27, 11.1%) had substantial mucinous differentiation. No EBV+ tumors had a mucinous phenotype. 115/402 (28.6%) of EBV-/MSS tumors had moderate to complete histopathological response, of which 23/115 (20.0%) had a mucinous phenotype. In resectable GC, MSI-high had favorable outcome compared to EBV-/MSS, both in patients treated with surgery only, and in those treated with perioperative chemo(radio)therapy. Substantial histopathological response was restricted to mucinous MSI-high tumors. The mucinous phenotype might be a relevant parameter in future clinical trials for MSI-high patients.


Induced pathophysiological alterations by the venoms of the most dangerous Moroccan scorpions Androctonus mauretanicus and Buthus occitanus: A comparative pathophysiological and toxic-symptoms study.
Scorpion envenomation is a serious public health issue. Androctonus mauretanicus (Am) and Buthus occitanus (Bo) are the most dangerous scorpions in Morocco. Despite their medical relevance, no study has yet related their kinetics of symptom apparition and the consequent tissue disorders at the same interval post-injection. This work achieved the first comparative pathophysiological and toxic-symptoms study between the Am and Bo venoms from a biochemical, toxicological and physiopathological standpoint. The activity of venoms and their subletal dose were determined by administration of increasing concentrations of the venoms. 30, 60 and 120 min following the experimental envenomation in mice, the profile of clinical symptoms was underlined and the main organs: brain, heart, lungs, liver and kidneys were removed for histological examination. The Am venom is a rich source of proteins and three-times more toxic than the Bo. The most observed clinical symptoms are neurological and cardiopulmonary. The Am venom caused histopathological alterations at 30, 60, and 120 min which were more important than the Bo. This study highlighted that both venoms exhibited a strong toxicity with variable intensities. Moreover, we showed the presence of correlation between the level of histopathological disorders observed and the intensity of signs appeared at the same time following venom inoculation.


Insular-opercular seizures manifesting with sleep-related paroxysmal motor behaviors: a stereo-EEG study.
Sleep-related complex motor seizures are a common feature of nocturnal frontal lobe epilepsy. Nevertheless, recent studies also suggest that sleep-related hypermotor seizures can originate in the insula. The present study describes the electroclinical features of eight drug-resistant epileptic patients with insular-opercular seizures manifesting with nocturnal complex motor seizures. Patients underwent a comprehensive presurgical evaluation, which included history, interictal electroencephalography (EEG), scalp video-EEG monitoring, high-resolution magnetic resonance imaging (MRI), and intracerebral recording by stereo-EEG. Almost all patients reported an initial sensation consisting of viscerosensitive or somatosensory symptoms. Ictal clinical signs were represented by tonic-dystonic asymmetric posturing and/or hyperkinetic automatisms, including bimanual/bipedal activity and ballistic movements. Some patients exhibited dysarthric speech, hypersalivation, and apnea. Interictal and ictal EEG provided lateralizing information in the majority of patients. In three patients, MRI showed a focal anatomical abnormality in the insular-opercular region. Stereo-EEG ictal recordings demonstrated that the epileptic discharge involved simultaneously the insular cortex and the opercular region. Complex motor manifestations appeared when the ictal discharge showed an extrainsular spreading to frontomesial regions (cingulum, superior frontal gyrus, and supplementary motor area) and/or to internal and neocortical temporal lobe structures. Six patients received an insular-opercular cortical resection; three of them are seizure free (minimum follow-up 24 months) and in one a marked reduction in seizure frequency was obtained. Two patients have been operated on recently. Histology revealed a focal cortical dysplasia in three patients. One patient excluded from surgery died for sudden unexpected death in epilepsy during sleep. Our data strengthen the concept that sleep-related complex motor attacks can originate in the insula, and provide useful electroclinical information to differentiate this localization from those with similar clinical characteristics. Furthermore, this study indicates that in these drug-resistant patients, surgical treatment represents a highly effective treatment option.


Influence of the different composites (PLA/PLLA/HA/β-TCP) contents manufactured with the use of additive laser technology on the biocompatibility.
In recent years, it has become extremely important to search for more and more natural and biocompatible materials that allow for the reconstruction of natural tissues with as few side effects as possible. The aim of the present paper is to define mechanical properties such as compressive stress and Young's Modulus and to estimate the ability of human bone cell strains to form biofilm on bioresorbable composites manufactured of polylactide and poly-l-lactide (PLA and PLLA) and hydroxyapatite and tricalcium phosphate (HA and β-TCP) with the use of Selective Laser Sintering (SLS) method. Microbiological tests were conducted on three variants of solid specimen made with additive laser technology. Samples with different chemical compositions were made with appropriate manufacturing parameters ensuring stability of both composite ingredients. Microbiological in vitro tests helped to determine cytotoxicity of specific samples toward bone cells. The results obtained indicate significantly increased ability of osteoblasts to form colonies on the surface of materials with higher content of hydroxyapatite ceramics compared to surfaces of lower hydroxyapatite content. The data provided can be useful for future applications of the SLS technology in production of bioresorbable PLA/PLLA/HA/β-TCP medical implants.


Co-teaching as science in the schoolhouse: more questions than answers.
The concept of science in the schoolhouse combines knowledge of research-based practices with the complexities of day-to-day life in schools. In this discussion, co-teaching is offered as an example of how advocacy for a practice can outpace the science that supports it. There is a push for co-teaching in contemporary schools, and special educators in great numbers are being asked to join with general educators in meeting the needs of students with disabilities. However, the science behind co-teaching to date is very limited. Studies have examined the implementation of co-teaching as a general service delivery option, but much less attention has been paid scientifically to the character and quality of the co-taught instruction or to the impact of co-teaching on student outcomes. Within this context, I also examine how Crockett's four recommendations to support science in the schoolhouse could address the questions about co-teaching for which there are few answers.


Maternal nutrition in pregnancy and the first postnatal year--2. After the birth.
In the second of a two-part article, a senior research scientist discusses the mother's nutritional needs during lactation and the first year after the birth. The mother's needs for energy increase during breast-feeding, but conversely studies have shown that breast-feeding mothers do not necessarily lose weight. As in pregnancy, it is recommended that all lactating women should take a supplement that provides 10 microg per day of vitamin D. Healthy diets for breastfeeding women are essentially the same as for other adults. Parents are often receptive to advice at this time and this is a good opportunity for health professionals to encourage breast-feeding and a healthy diet as this may promote future health.


Randomised phase III study of intravenous vinorelbine plus hormone therapy versus hormone therapy alone in hormone-refractory prostate cancer.
Vinorelbine (VRL) has been shown to be active in hormone-refractory prostate cancer (HRPC) in phase II studies, alone or in combination. Its moderate toxicity profile is well tolerated in elderly patients. Patients with metastatic prostate cancer, progressive after primary hormonal therapy, were randomised to receive intravenous VRL 30 mg/m2 on days 1 and 8 every 3 weeks, and hydrocortisone 40 mg/day or hydrocortisone alone until disease progression. Centres could choose to add aminoglutethimide 1000 mg/day to hydrocortisone as second-line hormone therapy (HT) for all their patients. Randomisation was stratified by centre. Further chemotherapy was allowed after progression. The primary end point was progression-free survival (PFS). The final analysis was performed on a total of 414 patients. Reported results were all based on intention-to-treat analyses. All progressions and responses were reviewed by an independent panel. PFS was significantly prolonged in the VRL plus HT arm compared with the HT alone arm, according to the statistical hypothesis of the protocol (P=0.055 in the two-sided log-rank test with a pre-specified significance level of 10%). The 6-month PFS rates were 33.2% versus 22.8%, and the median durations of PFS were 3.7 versus 2.8 months. In the multivariate Cox analysis, which included age, Karnofsky performance status (PS), haemoglobin, alkaline phosphatase at study entry and number of prior hormonal treatments, the P value was decreased to 0.005. The prostate-specific antigen (PSA) response rate (> or =50% decline sustained for at least 6 weeks) was significantly higher for VRL plus HT compared with HT (30.1% versus 19.2%; P=0.01). Clinical benefit, defined as a decrease in pain intensity or analgesic consumption or an improvement of Karnofsky PS for at least 9 weeks, and at least stable assessment in the other two, was also more frequently observed in patients who received VRL plus HT versus HT alone (30.6% and 19.2%; P=0.008). There was no statistical difference in overall survival. Forty-three per cent of patients in the HT arm received at least one line of further chemotherapy after progression, compared with 28% of patients in the VRL-based arm. Aminoglutethimide did not seem to result in better efficacy for either arm. VRL plus HT was well tolerated, with a median administered relative dose intensity of 90%; grade 4 neutropenia occurred in 6.5% of patients and non-haematological toxicity was rare. The combination of VRL and hydrocortisone compared with hydrocortisone alone resulted in improved clinical benefit, PFS and PSA response rate. This therapeutic gain is similar to that previously reported with mitoxantrone in combination with low-dose corticosteroids. There was no gain in survival; however, the combination is well tolerated in this elderly group of patients, who often present cardiac co-morbidities, and therefore offers an active and safe therapeutic option for patients with hormone-refractory prostate cancer.


SMN complex localizes to the sarcomeric Z-disc and is a proteolytic target of calpain.
Spinal muscular atrophy (SMA) is a recessive neuromuscular disease caused by mutations in the human survival motor neuron 1 (SMN1) gene. The human SMN protein is part of a large macromolecular complex involved in the biogenesis of small ribonucleoproteins. Previously, we showed that SMN is a sarcomeric protein in flies and mice. In this report, we show that the entire mouse Smn complex localizes to the sarcomeric Z-disc. Smn colocalizes with alpha-actinin, a Z-disc marker protein, in both skeletal and cardiac myofibrils. Furthermore, this localization is both calcium- and calpain-dependent. Calpains are known to release proteins from various regions of the sarcomere as a part of the normal functioning of the muscle; however, this removal can be either direct or indirect. Using mammalian cell lysates, purified native SMN complexes, as well as recombinant SMN protein, we show that SMN is a direct target of calpain cleavage. Finally, myofibers from a mouse model of severe SMA, but not controls, display morphological defects that are consistent with a Z-disc deficiency. These results support the view that the SMN complex performs a muscle-specific function at the Z-discs.


The effects of foot orthoses and sensory facilitation on lower limb electromyography: A scoping review.
Foot orthoses (FO) are used as a treatment for biomechanical abnormalities, overuse injuries, and neuropathologies, but study of their mechanism remains inconclusive. The neuromotor paradigm has proposed that FOs may manipulate sensory input from foot sole skin to reduce muscle activity for movement optimization. This review argues that a FO likely alters the incoming mechanical stimuli transmitted via cutaneous mechanoreceptors and nociceptors as the foot sole interfaces with the surface of the orthotic. Thus, all FOs with or without intentional sensory facilitation, likely changes sensory information from foot sole cutaneous afferents. Additionally, in light of understanding and applying knowledge pertaining to the cutaneous reflex loop circuitry, FO's increasing sensory input to the motorneuron pool can change EMG to either reflex sign (increase or decrease). The purpose of this scoping review was to synthesize FO and sensory augmentation literature and summarize how FO designs can capitalize on foot sole skin to modulate lower limb electromyography (EMG). Six database searches resulted in 30 FO studies and 22 sensory studies that included EMG as an outcome measure. Results revealed task and phase specific responses with some consistencies in EMG outcomes between testing modalities, however many inconsistencies remain. Electrical stimulation reflex research provides support for a likely sensory-to-motor factor contributing to muscle activity modulation when wearing FOs. The discussion divides trends in FO treatment modalities by desired increase or decrease in each compartment musculature. The results of this review provides a benchmark for future academics and clinicians to advance literature in support of a revised neuromotor paradigm while highlighting the importance of foot sole skin in FO design.


Pharmacokinetics of nitroxazepine in depressed patients.
A pharmacokinetic study was done on 10 depressed patients (DSM-III-R 296.3). The patients were treated with Sintamil (R) (nitroxazepine HCl) with titrated dose from 75 mg to 225 mg for 6 weeks. Plasma levels of nitroxazepine (Sintamil (R)) and its metabolites desmethyl (D), N-oxide (N-O) and carboxylic acid (c) were estimated. Anti-depressant efficacy was judged by reduction in Hamilton Rating Depression Scale (HDRS) scores, and tolerability was monitored by reports of unwanted effects.The overall reduction in HDRS score was about 50% by 6 weeks. The plasma levels of nitroxazepin (ng/ral) showed a rise from a mean ( +SEM) level. 47.0 4-7.3 on day 1 (dose 75 mg) to 129.84-24.6 on day 7 (dose 150 mg) (p< 0.01) and remained steady till day 21. There were large interindividual variations. The metabolites followed a similar pattern. The HDRS score showed a steady reduction between day 14 and 42 when the levels of nitroxizepine and des-methyl metabolites were maintained between 176.5 ng/ml to 251 ng/ml.


[Ef-Ts elongation factor interacts with elongation factor EF-Tu on ribosomes prior to the GTP hydrolysis stage].
Methods of high-speed centrifugation and limited proteolysis were used to probe the interaction of EF-Tu with EF-Ts on the ribosome. It is shown that EF-Ts dissociates from EF-Tu only after EF-Tu-mediated GTP hydrolysis, i.e. EF-Ts within the EF-Tu.ribosome complexes in the pre-GTP-hydrolysis state co-sediments with the ribosomes and its rate of proteolysis is distinct from that of free EF-Ts. Moreover, as seen from the difference in sensitivity to trypsin of ribosomal proteins L19 and L27 EF-Ts affects the interaction of EF-Tu with the ribosome.


Determining the dielectric constant inside pores of nanofiltration membranes from membrane potential measurements.
The membrane potential technique was applied to a nanofiltration polyamide membrane to determine its mean pore radius and the dielectric constant of electrolyte solutions inside pores. To our knowledge, this is the first attempt to assess these features from membrane potential measurements. Membrane potential data were analyzed by means of the SEDE (steric electric and dielectric exclusion) transport model. Experiments were conducted with single-salt solutions of NaCl and CaCl(2) and mixed-salt solutions of NaCl and CaCl(2) at various concentrations. It was shown that the pore-size values deduced from the high-concentration limit of the membrane potential measured with the two single-salt solutions are in good agreement. With this parameter being known, the membrane potential measured at high salt concentration with electrolyte mixtures was further used to compute the dielectric constant inside pores. The latter was found to be smaller than its bulk value and to decrease when sodium ions were replaced by calcium ions.


[Comparison of the three methods for estimating the dry-weight of hemodialysis patients].
In order to find the best method for estimating the dry-weight of hemodialysis (HD) patients, we compared the three methods used, i.e. bioelectrical resistivity (rho), plasma cGMP (cGMP) and bromide (Br) methods. The results showed that the extracellular fluid volume per unit body mass (EFV/mass) determined with rho was negatively correlated with that determined with Br. (r = -0.7601 for normal controls and -0.5293 for HD patients, P < 0.05). However, plasma cGMP concentration was neither correlated with EFV/mass (r = 0.3724 for normal control and 0.2538 for HD patients, P > 0.05) nor with rho (r = 0.5210 for normal controls and 0.2106 for HD patients, P > 0.05). These results suggest that the bioelectrical resistivity dry-weight method is more accurate than cGMP method and moreover it is easier to perform than the NaBr method.


Bayesian salamanders: analysing the demography of an underground population of the European plethodontid Speleomantes strinatii with state-space modelling.
It has been suggested that Plethodontid salamanders are excellent candidates for indicating ecosystem health. However, detailed, long-term data sets of their populations are rare, limiting our understanding of the demographic processes underlying their population fluctuations. Here we present a demographic analysis based on a 1996-2008 data set on an underground population of Speleomantes strinatii (Aellen) in NW Italy. We utilised a Bayesian state-space approach allowing us to parameterise a stage-structured Lefkovitch model. We used all the available population data from annual temporary removal experiments to provide us with the baseline data on the numbers of juveniles, subadults and adult males and females present at any given time. Sampling the posterior chains of the converged state-space model gives us the likelihood distributions of the state-specific demographic rates and the associated uncertainty of these estimates. Analysing the resulting parameterised Lefkovitch matrices shows that the population growth is very close to 1, and that at population equilibrium we expect half of the individuals present to be adults of reproductive age which is what we also observe in the data. Elasticity analysis shows that adult survival is the key determinant for population growth. This analysis demonstrates how an understanding of population demography can be gained from structured population data even in a case where following marked individuals over their whole lifespan is not practical.


alpha-Synuclein fission yeast model: concentration-dependent aggregation without plasma membrane localization or toxicity.
Despite fission yeast's history of modeling salient cellular processes, it has not yet been used to model human neurodegeneration-linked protein misfolding. Because alpha-synuclein misfolding and aggregation are linked to Parkinson's disease (PD), here, we report a fission yeast (Schizosaccharomyces pombe) model that evaluates alpha-synuclein misfolding, aggregation, and toxicity and compare these properties with those recently characterized in budding yeast (Saccharomyces cerevisiae). Wild-type alpha-synuclein and three mutants (A30P, A53T, and A30P/A53T) were expressed with thiamine-repressible promoters (using vectors of increasing promoter strength: pNMT81, pNMT41, and pNMT1) to test directly in living cells the nucleation polymerization hypothesis for alpha-synuclein misfolding and aggregation. In support of the hypothesis, wild-type and A53T alpha-synuclein formed prominent intracellular cytoplasmic inclusions within fission yeast cells in a concentration- and time-dependent manner, whereas A30P and A30P/A53T remained diffuse throughout the cytoplasm. A53T alpha-synuclein formed aggregates faster than wild-type alpha-synuclein and at a lower alpha-synuclein concentration. Unexpectedly, unlike in budding yeast, wild-type and A53T alpha-synuclein did not target to the plasma membrane in fission yeast, not even at low alpha-synuclein concentrations or as a precursor step to forming aggregates. Despite alpha-synuclein's extensive aggregation, it was surprisingly nontoxic to fission yeast. Future genetic dissection might yield molecular insight into this protection against toxicity. We speculate that alpha-synuclein toxicity might be linked to its membrane binding capacity. To conclude, S. pombe and S. cerevisiae model similar yet distinct aspects of alpha-synuclein biology, and both organisms shed insight into alpha-synuclein's role in PD pathogenesis.


[Dynamics of Cry1ab protein content in the rhizosphere soil and straw debris of transgenic Bt corn].
By using ELISA test kits, a field investigation was conducted on the degradation dynamics of CrylAb protein in the rhizosphere soil of Bt corn MON810 at its different growth stages and in the MON810 straws returned into field after harvest. Three models (shift-log model, exponential model, and bi-exponential model) were used to fit the degradation dynamics of the Cry1 Ab protein from the straw debris, and the DT50 and DT90, values were estimated. There existed great differences in the CrylAb protein content in the rhizosphere soil of MON810 at its different growth stages, but overall, the CrylAb protein content was decreased remarkably with the growth of MON810. The degradation of Cry1 Ab protein from the straws covered on soil surface and buried in soil showed the same two-stage pattern, i.e., more rapid at early stage and slow-stable in later period. Within the first week after straw return, the degradation rate of the CrylAb protein from the straws covered on soil surface was significantly higher than that from the straws buried in soil. At 10 d, the degradation rate of the CrylAb protein from the straws covered on soil surface and buried in soil was basically the same, being 88.8% and 88.6%, respectively. After 20 days, the degradation of CrylAb protein entered slow-stable stage. Till at 180 d, a small amount of Cry1Ab protein could still be detected in the straw debris. All of the three models used in this study could fit the decay pattern of the CrylAb protein from the straw debris in field. By comparing the correlation coefficient (r) and the consistency between the measured and calculated DT90, bi-exponential model was considered to be the best.


[Effectiveness of simultaneous combination therapy using S-1, nedaplatin and radiotherapy for 7 cases of oropharynx cancer].
Various treatments for oropharynx cancer included radiotherapy, arterial injection chemotherapy (as well as combined chemoradiotherapy), combined concurrent chemoradiotherapy, and surgical resection and reconstruction. There are also treatment differences among facilities. Our department has been providing a treatment modality for head and neck malignancies with the aims of functional and morphological preservation with a high cure rate. We herein report the treatment efficacy in 7 cases of oropharynx cancer (6 cases on lateral wall and 1 case on superior wall)treated with S-1, nedaplatin and radiotherapy (SN therapy) at our department between April 2006 and December 2006. The total of 7 cases included 1 case of T1N1M0, 1 of T2N0M0, 2 of T2N2bM0, 1 of T2N2cM0, 1 of T3N2cM0, and 1 case of T4N2cM0. The patients were all male and their ages ranged from 57 to 76 years old, with the average age of 68.4 years. Six of the 7 cases are surviving without cancer through treatment and their functions and morphologies have been preserved. In the 1 case of T4N2cM0, the tumor did not disappear and the patient expired due to the original lesion. Although SN therapy supposedly enables functional and morphological preservation, it is necessary to increase the number of cases and examine the efficacy of SN therapy for oropharynx cancer for functional and morphological preservation and the survival rate.


Nuclear translocation of nuclear factor kappa B in early 1-cell mouse embryos.
Nuclear factor kappa B (NF-kappaB) is a transcription factor that controls the expression of a number of genes under cellular redox potential. It has recently been found that NF-kappaB plays a pivotal role in morphogenesis and embryonic development, e.g., in formation of Drosophila malanogaster ventral structures and chicken limb buds. However, the role of NF-kappaB in preimplantation development in mammals is not yet understood. In this study, we show that RelA, one of the subunits of NF-kappaB, is expressed in mouse eggs and embryos from the metaphase II (MII) oocyte to the blastocyst stage. Therefore, it is thought that RelA is maternally expressed and that it continues to be expressed during preimplantation development. Immunofluorescence analysis showed that RelA protein was mainly distributed in the cytoplasm of embryos, whereas nuclear translocation of RelA, evidence for NF-kappaB activation, was observed only at the early 1-cell stage. Finally we studied the effects of NF-kappaB inhibitors, pyrrolidine dithiocarbamate and N-acetyl-L-cysteine, on the preimplantation development of mouse embryos. When these inhibitors were added to the culture medium from the early 1-cell stage, subsequent development through the 2-cell stage was inhibited. However, little, if any, influence on the progression through the 2-cell stage was observed when the inhibitors were added at the late 1-cell or the 2-cell stage. Taken together, the results suggest that the activation of NF-kappaB at the early 1-cell stage is required for the development of mouse embryos beyond the 2-cell stage.


Stabilisation surgery for chronic low back pain: indications, surgical procedures, and outcome.
Spinal fusion was introduced as a treatment option for chronic low back pain >70 years ago. However, few areas of spinal surgery have caused as much controversy. The debate about whether to use an anterior-, posterior- or anterior + posterior approach has persisted since the 1930s. Within the last 10 years, the effects of different spinal fusion procedures have been tested in 10 randomized controlled trails (RCT). A highly significant improvement over preoperative status was found in all 10 studies. Two recent RCTs have dealt with the question of conservative versus operative treatment of patients with low back pain, and both studies have shown a significant better functional outcome for spinal fusion in situ, compared with a more or less organized exercise programme at 2-year follow-up. The choice of postoperative rehabilitation strategy has also been shown to be of importance for overall functional outcome. One study has demonstrated the importance of the inclusion of coping schemes, and questioned the role of intensive exercises in a rehabilitation programme for spinal fusion patients.


Retinopetal neurons located in the diencephalon of the Japanese monkey (Macaca fuscata).
After a monocular injection of the cholera toxin B subunit (CTB) into the vitreous chamber of one eye, the retrogradely labeled retinopetal neurons were studied in the diencephalon of the Japanese monkey. The retrogradely transported tracer was visualized using the peroxidase antibody technique and an anti-cholera toxin antibody. The CTB-labeled nerve cell bodies were scattered in the periventricular nucleus of the hypothalamus, lateral hypothalamic area, and midline nuclei of the thalamus on both sides. In addition, a few retrogradely labeled nerve somata were observed in the most rostral portion of the lateral geniculate nucleus on the contralateral side.


Enantioselective synthesis of cyclohexenone derivatives by a chemicoenzymatic approach: stereo- and regioselective route to potential intermediates of compactin (ML 236B) and mevinolin.
As a synthetic application of the chiral monoester 2, prepared by pig liver esterase (PLE)-catalyzed hydrolysis of the corresponding meso diester 1, conversion of 2 into various cyclohexenone derivatives was examined. This paper describes the preparation of the isomeric cyclohexenones 6 and 7, potential intermediates for the synthesis of anti-hypercholesmic compactin (ML 236B) and mevinolin, under stereo- and regioselective control.


Selective formation of spiro dihydrofurans and cyclopropanes through unexpected reaction of aldehydes with 1,3-dicarbonyl compounds.
An efficient methodology for the oxidative addition reaction of various aldehydes with 5,5-dimethylcyclohexane-1,3-dione and 1,3-indandione to selectively afford spiro dihydrofuran and cyclopropane derivatives, promoted by molecular iodine and dimethylaminopyridine under mechanical milling conditions, has been demonstrated. The products were obtained in good to excellent yields. A possible mechanism of this unusual reaction process is proposed.


[Computer tomography of esthesioneuroblastoma].
Aesthesioneuroblastomas are rare malignant nasal tumours of neural origin. Clinical symptoms depend upon the extent of the lesion. Five cases of tomography visualised the tumours as non-homogeneous soft tissue masses in the nasal cavity and the ethmoid cells with a varying infiltration of the adjacent paranasal sinuses. Radical surgery and radiation therapy are recommended. CT should be an integral part of annual follow-up studies.


A Year into the Pandemic: An Update on Women in Science, Technology, Engineering, Math, and Medicine.
The coronavirus pandemic revealed long-standing, unaddressed fissures in our systems, including dramatic gender inequities in science, technology, engineering, mathematics, and medicine (STEMM) fields. Women have disproportionately carried the burden of childcare and other caregiving responsibilities during the pandemic, and there are strong indications that the pandemic will likely exacerbate preexisting disparities in the pipeline of women in STEMM and in leadership positions. Based on a literature review, our own experiences, and the experiences of our colleagues, we review promising strategies that have been implemented by funding bodies, journals, professional societies, and colleges/universities as well as additional strategies that might be helpful for these entities to implement to move forward with policies in place that address gender inequities and rebuild our institutional systems better. At this moment in time, institutions should collect data on metrics such as recruitment, retention, tenure/promotion, funding, professional society membership, awards/honors, and scientific publishing. These data will be essential in determining the impact of policies on women in STEMM to ensure they are having the intended effect as well as what future actions might be necessary in an iterative process.


Inhibition studies of soybean (Glycine max) urease with heavy metals, sodium salts of mineral acids, boric acid, and boronic acids.
Various inhibitors were tested for their inhibitory effects on soybean urease. The K(i) values for boric acid, 4-bromophenylboronic acid, butylboronic acid, and phenylboronic acid were 0.20 +/- 0.05 mM, 0.22 +/- 0.04 mM, 1.50 +/- 0.10 mM, and 2.00 +/- 0.11 mM, respectively. The inhibition was competitive type with boric acid and boronic acids. Heavy metal ions including Ag(+), Hg(2+), and Cu(2+) showed strong inhibition on soybean urease, with the silver ion being a potent inhibitor (IC(50) = 2.3 x 10(-8) mM). Time-dependent inhibition studies exhibited biphasic kinetics with all heavy metal ions. Furthermore, inhibition studies with sodium salts of mineral acids (NaF, NaCl, NaNO(3), and Na(2)SO(4)) showed that only F(-) inhibited soybean urease significantly (IC(50) = 2.9 mM). Competitive type of inhibition was observed for this anion with a K(i) value of 1.30 mM.


Fishing anti(lymph)angiogenic drugs with zebrafish.
Zebrafish, an amenable small teleost fish with a complex mammal-like circulatory system, is being increasingly used for drug screening and toxicity studies. It combines the biological complexity of in vivo models with a higher-throughput screening capability compared with other available animal models. Externally growing, transparent embryos, displaying well-defined blood and lymphatic vessels, allow the inexpensive, rapid, and automatable evaluation of drug candidates that are able to inhibit neovascularisation. Here, we briefly review zebrafish as a model for the screening of anti(lymph)angiogenic drugs, with emphasis on the advantages and limitations of the different zebrafish-based in vivo assays.


Safe practice in syringe pump management.
Syringe pumps offer an alternative route for delivering medicine when the oral route cannot be used. This is particularly important for patients receiving palliative care, for whom a continuous infusion of medication can improve symptom control. This article explains how to administer drugs safely using these devices.


Therapeutic potential and safety considerations for the clinical use of synthetic cannabinoids.
The phytocannabinoid Δ9-tetrahydrocannabinol (THC) was isolated and synthesized in the 1960s. Since then, two synthetic cannabinoids (SCBs) targeting the cannabinoid 1 (CB1R) and 2 (CB2R) receptors were approved for medical use based on clinical safety and efficacy data: dronabinol (synthetic THC) and nabilone (synthetic THC analog). To probe the function of the endocannabinoid system further, hundreds of investigational compounds were developed; in particular, agonists with (1) greater CB1/2R affinity relative to THC and (2) full CB1/2R agonist activity. This pharmacological profile may pose greater risks for misuse and adverse effects relative to THC, and these SCBs proliferated in retail markets as legal alternatives to cannabis (e.g., novel psychoactive substances [NPS], "Spice," "K2"). These SCBs were largely outlawed in the U.S., but blanket policies that placed all SCB chemicals into restrictive control categories impeded research progress into novel mechanisms for SCB therapeutic development. There is a concerted effort to develop new, therapeutically useful SCBs that target novel pharmacological mechanisms. This review highlights the potential therapeutic efficacy and safety considerations for unique SCBs, including CB1R partial and full agonists, peripherally-restricted CB1R agonists, selective CB2R agonists, selective CB1R antagonists/inverse agonists, CB1R allosteric modulators, endocannabinoid-degrading enzyme inhibitors, and cannabidiol. We propose promising directions for SCB research that may optimize therapeutic efficacy and diminish potential for adverse events, for example, peripherally-restricted CB1R antagonists/inverse agonists and biased CB1/2R agonists. Together, these strategies could lead to the discovery of new, therapeutically useful SCBs with reduced negative public health impact.


Fractional flow reserve-CT assessment of coronary stenosis.
Coronary computed tomography angiography (CCTA) has been an established noninvasive method for detection of coronary artery disease (CAD). Although CCTA has had a high sensitivity and negative predictive value for CAD detection, specificity for obstructive CAD has been relatively low, partly due to coronary calcium, imaging artifacts, and other factors leading to an overestimation of stenosis severity. A relatively new noninvasive method of calculation of fractional flow reserve (FFR) using CCTA (FFRCT ) data has been developed. This noninvasive method yields similar results to invasive FFR measurement, improving specificity for noninvasively detecting lesion-specific ischemia thus helping guide revascularization.


Cardiac arrest, chain of survival and Utstein style.
Cardiac arrest is a dramatic condition leading to sudden death if someone cannot perform two interventions, basic life support and early defibrillation, that have been proved to improve long-term survival. The modern era of cardiopulmonary resuscitation began with a description of closed chest cardiac massage by Kouwenhoven in 1960. Research to make advances in cardiac arrest is a very difficult task. Experts set up a series of guidelines that represent a keystone for educational needs and evolving technology. There is a consensus that the highest potential survival rate from cardiac arrest can only be achieved when the following sequence of events occurs as rapidly as possible: (1) recognition of early warning signs, (2) activation of the emergency medical services, (3) basic cardiopulmonary resuscitation, (4) cardiac defibrillation, (5) management of the airway and ventilation of the lungs, and (6) intravenous (i.v.) administration of medications. These events are necessary for any success of emergency cardiovascular care. They are linked in a chain of survival. The links in the adult chain of survival are: early access; early CPR; early defibrillation; and early acute cardiac life support. The 'Utstein style', recently introduced, represents a standard of practice both inside and outside hospital with recommended guidelines for the uniform reporting of clinical data from the patient suffering cardiac arrest. According to the concept of the chain of survival, the Utstein style delineates time and establishes a set of core and supplemental times to be recorded that provide important characteristics of the response of victims of cardiac arrest.


Assessment of deep venous thrombosis in the lower limbs and pelvis: MR venography versus duplex Doppler sonography.
This study was designed to compare the diagnostic value of MR venography and color Doppler sonography in the assessment of deep venous thrombosis. MR venograms and color Doppler examinations were obtained in 37 patients either with suspected deep venous thrombosis of the lower limbs or pelvis or with pulmonary embolism. Two-dimensional time-of-flight venography was used for all studies. MR and color Doppler data were collected prospectively and analyzed in a blinded manner. In a subset of 21 patients, MR venography and color Doppler sonography were prospectively compared with contrast-enhanced venography. When compared with contrast-enhanced venography, MR venography was 100% sensitive and 100% specific in the diagnosis of deep venous thrombosis above the knee. Color Doppler imaging depicted 13 of 15 cases of deep venous thrombosis and 5 of 6 venous examinations that had normal results, yielding a sensitivity and a specificity of 87% and 83%, respectively. The differences in sensitivity and specificity between MR venography and color Doppler sonography were not statistically significant. MR venography was 95% sensitive and 99% specific in detecting the extension of deep venous thrombosis, compared with the 46% sensitivity and 100% specificity of color Doppler sonography (differences in sensitivity, p < .01). MR images showed 29 collateral vessels, whereas only 21 were detected by contrast-enhanced venography (p < .04). MR venography seems to be more accurate than color Doppler sonography in detecting the extension of deep venous thrombosis. The positive diagnosis and extent of deep venous thrombosis can be easily detected and monitored by a noninvasive technique such as MR venography.


Association of Oral Health Conditions in Adolescents with Social Factors and Obesity.
This study aimed to investigate associations between psychosocial factors, obesity, and oral health in a study population of 10- to 18-year-old adolescents who participated in the LIFE Child study. Psychosocial information (socioeconomic status (SES) based on parents' education, occupation and household income, Strengths and Difficulties Questionnaire (SDQ), health-related quality of life) and physical activity behavior were obtained. Nutritional status was classified based on age- and sex-adjusted body mass index into underweight, overweight, normal weight and obese. Clinical dental examinations were performed and scored with respect to caries experience (CE), oral hygiene (OH), and periodontal status (periodontal health score: PERIO-S). Age-adjusted regression analysis under the assumption of a double Poisson distribution was performed with and without adjusting for SES (α = 5%). A total of 1158 study participants (590 girls, 568 boys; mean age 13.2 ± 2.3 years) were included (17.2% were classified as obese). CE was 20% higher for moderate and 60% higher for low SES compared to high SES (p < 0.05). PERIO-S was 10% higher for moderate and 30% higher for low compared to high SES (p < 0.05). Poor OH was associated with higher CE (Ratio R = 2.3, p < 0.0001) and PERIO-S (R = 3.1, p < 0.0001). Physical activity in a sports club was associated with lower CE-S and PERIO-S (R = 0.85, p < 0.001). Obesity was associated with increased CE (R = 1.3, p < 0.001) compared to normal weight. For low but not high SES, more reported difficulties were associated with higher CE. In conclusion, low SES, poor OH, and obesity are associated with unfavorable oral health conditions, whereas physical activity and high SES are potentially protective.


Plasma tumor DNA: on your markers, get set, go!
Metastatic breast cancer is incurable, yet highly treatable with endocrine, HER2 directed and chemotherapies improving survival for many patients. Successful treatment depends on the ability to monitor disease burden and response to therapies. Recently, a proof of principle study has shown that plasma tumor DNA (ptDNA) can be used as a reliable breast cancer biomarker in metastatic disease, due to its sensitivity and wide dynamic range. ptDNA more accurately reflects changes in response to therapies, and absolute levels of ptDNA demonstrate prognostic significance. Thus, ptDNA as a liquid biopsy shows great promise in the clinical management of metastatic breast cancer though further technical challenges and larger confirmatory studies are needed.


Bulimia and impulsive behaviour in middle adolescence.
In clinical samples, bulimia seems to be associated with various dyscontrol behaviours suggesting weakness in impulse control. Population studies of adolescents, however, are needed. We evaluated the association between self-reported bulimic behaviour and a number of dyscontrol behaviours, namely bullying, truancy, excessive drinking and sexual disinhibition among adolescents aged 14-16. This is the first study on bulimia and impulsivity in a large non-selected adolescent population sample. A self-report questionnaire was administered to a representative population sample of 14- to 16-year-old adolescents (pupils of the 8th and the 9th grades of secondary school in four different regions in Finland). 4,453 girls and 4,334 boys aged 14-16 participated. The participation rate was 85.5%. Bulimic behaviour was associated with bullying, truancy, excessive drinking and sexual disinhibition among both sexes. Odds ratios for bulimic-type eating pathology according to each of these behaviours varied between 1.7 and 4.1. The more dyscontrol behaviours occurred simultaneously, the more likely was bulimic-type eating pathology. There is an association between bulimic behaviour and dyscontrol behaviours in the general population of adolescent girls and boys.


Ofuji's disease: a report on 20 patients with clinical and histopathologic analysis.
Ofuji's disease, also referred to as classic eosinophilic pustular folliculitis, is a rare dermatosis of unknown origin for which there is no uniformly effective treatment. Twenty patients with Ofuji's disease (classic eosinophilic pustular folliculitis) evaluated in our department from January 1978 to June 1999 were studied clinically and histopathologically. Laboratory data, treatments, and clinical courses were evaluated in 12 of these individuals. Nissl modified staining revealed moderate increases of mast cells around hair follicles and sebaceous glands in all 20 patients; the majority of the infiltrating mast cells were tryptase-positive and chymase-negative. Eight of 11 patients treated with oral indomethacin responded completely. Indomethacin is an effective therapy for Ofuji's disease. Tryptase-positive and chymase-negative mast cells might play some role in the pathogenesis of Ofuji's disease.


Transcriptional regulation of mesoderm genes by MEF2D during early Xenopus development.
In Xenopus, specification of the three germ layers is one of the earliest developmental decisions occurring prior to gastrulation. The maternally-expressed vegetally-localized transcription factor VegT has a central role in cell autonomous specification of endoderm and in the generation of mesoderm-inducing signals. Yet, marginally-expressed transcription factors that cooperate with mesoderm-inducing signals are less investigated. Here we report that the transcription factors MEF2A and MEF2D are expressed in the animal hemisphere before mid-blastula transition. At the initiation of zygotic transcription, expression of MEF2D expands into the marginal region that gives rise to mesoderm. Knockdown of MEF2D delayed gastrulation movements, prevented embryo elongation at the subsequent tailbud stage and caused severe defects in axial tissues. At the molecular level, MEF2D knockdown reduced the expression of genes involved in mesoderm formation and patterning. We also report that MEF2D functions with FGF signaling in a positive feedback loop; each augments the expression of the other in the marginal region and both are necessary for mesodermal gene expression. One target of MEF2D is the Nodal-related 1 gene (Xnr1) that mediates some of MEF2D mesodermal activities. Chromatin immunoprecipitation analysis revealed that MEF2D associates with transcriptional regulatory sequences of the Xnr1 gene. Several MEF2 binding sites within the proximal promoter region of Xnr1 were identified by their in vitro association with MEF2D protein. The same promoter region was necessary but not sufficient to mediate MEF2D activity in a reporter gene assay. In sum, our results indicate that the MEF2D protein is a key transcription factor in the marginal zone acting in a positive feedback loop with FGF signaling that promotes mesoderm specification at late blastula stages.


'Clinical trials in Alzheimer's disease': immunotherapy approaches.
Recent advances in the understanding of Alzheimer's disease pathogenesis have led to the development of numerous compounds that might modify the disease process. Amyloid β (Aβ) peptide represents an important molecular target for intervention in Alzheimer's disease. Several types of Aβ peptide immunotherapy for Alzheimer's disease are under investigation, direct immunization with synthetic intact Aβ(42) , active immunization involving the administration of synthetic fragments of Aβ peptide conjugated to a carrier protein and passive administration with monoclonal antibodies directed against Aβ peptide. Pre-clinical studies showed that immunization against Aβ peptide can provide protection and reversal of the pathology of Alzheimer's disease in animal models. Indeed, several adverse events have been described like meningoencephalitis with AN1792, vasogenic edema and microhemorrhages with bapineuzumab. Although immunotherapy approaches resulted in clearance of amyloid plaques in patients with Alzheimer's disease, this clearance did not show significant cognitive effect for the moment. Currently, several Aβ peptide immunotherapy approaches are under investigation but also against tau pathology.


Photosynthesis and Ribulose 1,5-Bisphosphate Concentrations in Intact Leaves of Xanthium strumarium L.
The interacting effects of the rate of ribulose 1,5-bisphosphate (RuBP) regeneration and the rate of RuBP utilization as influenced by the amount and activation of RuBP carboxylase on photosynthesis and RuBP concentrations were resolved in experiments which examined the kinetics of the response of photosynthesis and RuBP concentrations after step changes from a rate-saturating to a rate-limiting light intensity in Xanthium strumarium. Because RuBP carboxylase requires several minutes to deactivate in vivo, it was possible to observe the effect of reducing the rate of RuBP regeneration on the RuBP concentration at constant enzyme activation state by sampling very soon after reducing the light intensity. Samples taken over longer time periods showed the effect of changes in enzyme activation at constant RuBP regeneration rate on RuBP concentration and photosynthetic rate. Within 15 s of lowering the light intensity from 1500 to 600 microEinsteins per square meter per second the RuBP concentration in the leaves dropped below the enzyme active site concentration, indicating that RuBP regeneration rate was limiting for photosynthesis. After longer intervals of time, the RuBP concentration in the leaf increased as the RuBP carboxylase assumed a new steady state activation level. No change in the rate of photosynthesis was observed during the interval that RuBP concentration increased. It is concluded that the rate of photosynthesis at the lower light intensity was limited by the rate of RuBP regeneration and that parallel changes in the activation of RuBP carboxylase occurred such that concentrations of RuBP at steady state were not altered by changes in light intensity.


Oropharyngeal lesions and cervical lymphadenopathy: syphilis is a differential diagnosis that is still relevant.
Syphilis (lues), a chronic infectious disease caused by Treponema pallidum, has been increasing in incidence during the last few years. Therefore, while clinically it is often not suspected, syphilis is increasingly becoming a differential diagnosis in routine pathology. To report our experience with five cases of cervical lymphadenopathy and/or oropharyngeal lesions, clinically thought to be lymphomas, lymph node metastases or carcinoma, in which we made the mostly clinically unsuspected diagnosis of syphilis. Fine needle aspiration of enlarged cervical lymph nodes was evaluated by cytology and flow cytometry (fluorescence-activated cell sorting analysis), and biopsies were examined by using histology. In addition, all materials were also subjected to immunostaining, silver staining and molecular (PCR) testing. Fine needle aspiration cytology revealed follicular hyperplasia in two cases and granulomatous lymphadenitis in one case. In three patients, concomitant biopsy of co-existing oropharyngeal lesions revealed histological findings compatible with syphilis. T pallidum was detected in all cytological and histological samples by immunohistochemistry/immunocytochemistry and PCR. Subsequently, a diagnosis of syphilis was confirmed clinically and by serology. Syphilitic lymphadenitis is still a relevant differential diagnosis of cervical lymphadenopathy, and it is clinically often not suspected. Co-existing oropharyngeal lesions should alert the physician to this differential diagnosis; and lesions with compatible morphology should be tested with immunohistochemistry and immunocytochemistry and/or molecular analysis to confirm the diagnosis of syphilis.


Reading in the dark: effects of age and contrast on reading speed and comprehension.
To explore the effects of contrast reduction on younger and older adults' reading behavior and to examine whether readers rely on word predictability to compensate for poor contrast. Poor contrast can degrade text and may influence reading behavior. Readers may compensate for visual degradation of text by taking advantage of word predictability. In Experiment 1, 5 younger and 5 older adults read sentences presented with 10 levels of contrast. In Experiment 2, 40 younger and 40 older adults read high-, medium-, and low-contrast sentences that varied in target word predictability (high vs. low). Relative to those of younger adults, older adults' reading rates were more slowed by low contrast; comprehension was less influenced by contrast (i.e., not significantly). Older adults read high-predictability words faster and comprehended them better than low-predictability words, significantly so for high- and medium-contrast sentences. Younger adults comprehended high-predictability words significantly better than low-predictability words for high- and low-contrast sentences. Low contrast was more detrimental for older adults. High-predictability words benefited older adults by significantly reducing their reading times and benefited all readers by significantly increasing their comprehension. The current findings demonstrate the benefit of adequate contrast and word predictability for optimal text design to facilitate both reading times and reading comprehension.


A Delphi study to determine informatics competencies for nurses at four levels of practice.
Despite its obvious need, a current, research-based list of informatics competencies for nurses is not available. To produce a research-based master list of informatics competencies for nurses and differentiate these competencies by level of nursing practice. After a comprehensive literature review and item consolidation, an expert panel defined initial competencies. Subsequently, a three round Delphi study was conducted to validate the items. Participants were expert informatics nurse specialists in the United States of America. Of the initial 305 competencies proposed, 281 competencies achieved an 80% or greater agreement for both importance as a competency and appropriateness for the correct practice level. Five competencies were rejected. Six competencies were considered valid competencies but the appropriate level of practice could not be agreed upon. Thirteen competencies did not reach any consensus after the three Delphi rounds. The Delphi study had a high rate of participation, demonstrating the great level of interest and need for a list of informatics competencies for nurses. Out of the initial 305 competencies, only 24 items were not validated. Respondents commented during each round about whether computer skills should be considered informatics competencies. The authors propose that computer skills, while not high level, are one set of tools within the larger category of informatics competencies. This sample of experts did not deem programming skills as necessary for informatics nurses. This research study is an initial effort to fill the void of valid and reliable informatics competencies. It is the first study to span four levels of nurses, create competencies for both entry-level and experienced informatics nurse specialists, and examine the categories of computer skills, informatics knowledge and informatics skills.


Molecular pathogenesis of peripheral neuropathies: insights from Drosophila models.
Peripheral neuropathies are characterized by degeneration of peripheral motor, sensory and/or autonomic axons, leading to progressive distal muscle weakness, sensory deficits and/or autonomic dysfunction. Acquired peripheral neuropathies, e.g., as a side effect of chemotherapy, are distinguished from inherited peripheral neuropathies (IPNs). Drosophila models for chemotherapy-induced peripheral neuropathy and several IPNs have provided novel insight into the molecular mechanisms underlying axonal degeneration. Forward genetic screens have predictive value for discovery of human IPN genes, and the pathogenicity of novel mutations in known IPN genes can be evaluated in Drosophila. Future screens for genes and compounds that modify Drosophila IPN phenotypes promise to make valuable contributions to unraveling the molecular pathogenesis and identification of therapeutic targets for these incurable diseases.


Evaluation: Imaging Studies.
The malignant or benign nature of a salivary gland (SG) tumor can be predicted with reasonably high accuracy by imaging. There is some overlap between the imaging findings of benign and malignant tumors, particularly for low-grade malignancies, and tissue diagnosis remains necessary for definitive diagnosis. Magnetic resonance imaging is the modality of choice for the evaluation of salivary neoplasms, as it allows for delineation of local infiltration, perineural spread and intracranial extension. This review will focus on the advanced imaging techniques that help to characterize SG tumors. A brief overview of the conventional imaging features of SG neoplasms is necessary before a discussion of the advanced imaging methods.


Decentralization of Next-Generation RNA Sequencing-Based MammaPrint® and BluePrint® Kit at University Hospitals Leuven and Curie Institute Paris.
A previously developed and centrally validated MammaPrint® (MP) and BluePrint® (BP) targeted RNA next-generation sequencing (NGS) kit was implemented and validated in two large academic European hospitals. Additionally, breast cancer molecular subtypes by MP and BP RNA sequencing were compared with immunohistochemistry (IHC). Patients with early breast cancer diagnosed at University Hospitals Leuven and Curie Institute Paris were prospectively included between September 2017 and January 2018. Formalin-fixed paraffin-embedded tissue sections were analyzed with MP and BP NGS technology at the beta sites and with both NGS and microarray technology at Agendia. Raw NGS data generated on Illumina MiSeq instruments at the beta sites were interpreted and compared with NGS and microarray data at Agendia. MP and BP NGS molecular subtypes were compared to surrogate IHC breast cancer subtypes. Equivalence of MP and BP indices was determined by Pearson's correlation coefficient. Acceptable limits were defined a priori, based on microarray data generated at Agendia between 2012 and 2016. The concordance, the Negative Percent Agreement and the Positive Percent Agreement were calculated based on the contingency tables and had to be equal to or higher than 90%. Out of 124 included samples, 48% were MP Low and 52% High Risk with microarray. Molecular subtypes were BP luminal, HER2 or basal in 82%, 8% and 10% respectively. Concordance between MP microarray at Agendia and MP NGS at the beta sites was 91.1%. Concordance of MP High and Low Risk classification between NGS at the beta sites and NGS at Agendia was 93.9%. Concordance of MP and BP molecular subtyping using NGS at the beta sites and microarray at Agendia was 89.5%. Concordance between MP and BP NGS subtyping, and IHC was 71.8% and 76.6%, for two IHC surrogate models. The MP/BP NGS kit was successfully validated in a decentralized setting.


Endothelial denudation combined with embolization in the prevention of endoleaks after endovascular aneurysm repair: an animal study.
To test whether combining embolization with endothelial denudation could reduce endoleak persistence and recurrence after endovascular aneurysm repair (EVAR) in an animal model. Type I endoleaks with collateral outflow were created in bilateral iliac aneurysms in 12 dogs. In 6 animals (group 1), endoleaks were treated by thrombin injection, with or without mechanical denudation of the endothelium. In the other 6 animals (group 2), simultaneous occlusion and endothelial denudation was induced in one side by treatment with a gel containing ethanol, ethylcellulose, and lipiodol, whereas the other side was treated with saline control. Follow-up ultrasonography and angiography were performed before necropsy and histology at 3 months. Denudation combined with thrombin injection led to higher aneurysm shrinkage than thrombin alone, as shown by the mean relative aneurysm diameter (89% vs. 124% at baseline, p<0.01) and length (61% vs. 82% at baseline, p<0.01). Denudation did not significantly reduce endoleak occurrence (4/6 vs. 6/6); however, endoleaks in denuded aneurysms were significantly smaller and located in areas inaccessible to denudation. Six of the 10 endoleaks seen at 3 months occurred despite complete initial occlusion (recurrent endoleaks). In the gel-treated group, embolized aneurysms did not shrink significantly, and stent-graft thrombosis developed in 3/6 embolized aneurysms; however, the 3 other aneurysms showed no endoleaks, while all 6 saline-treated controls exhibited persistent endoleaks. This study demonstrates the role of recanalization in endoleak recurrence and indicates that combining embolization and endothelial denudation could be a promising strategy to prevent endoleak persistence or recurrence after EVAR. However, the sclerosing gel tested in this study is not appropriate since it is prone to migration with resultant stent-graft thrombosis.


The Recovery of Muscle Spindle Sensitivity Following Stretching Is Promoted by Isometric but Not by Dynamic Muscle Contractions.
It is often suggested that stretching-related changes in performance can be partially attributed to stretching-induced neural alterations. Recent evidence though shows that neither spinal nor cortico-spinal excitability are susceptible of a long-lasting effect and only the amplitude of stretch or tap reflex (TR) is reduced up to several minutes. Since afferents from muscle spindles contribute to voluntary muscle contractions, muscle stretching could be detrimental to muscle performance. However, the inhibition of muscle spindle sensitivity should be reversed as soon as the stretched muscle contracts again, due to α-γ co-activation. The present work evaluated which type of muscle contraction (static or dynamic) promotes the best recovery from the inhibition in spindle sensitivity following static stretching. Fifteen students were tested for TR at baseline and after 30 s maximal individual static stretching of the ankle plantar flexors followed by one of three randomized interventions (isometric plantar flexor MVC, three counter movement jumps, and no contraction/control). Ten TRs before and 20 after the procedures were induced with intervals of 30 s up to 10 min after static stretching. The size of the evoked TRs (peak to peak amplitude of the EMG signal) following stretching without a subsequent contraction (control) was on average reduced by 20% throughout the 10 min following the intervention and did not show a recovery trend. Significant decrease in relation to baseline were observed at 9 of the 20 time points measured. After MVC of plantar flexors, TR recovered immediately showing no differences with baseline at none of the investigated time points. Following three counter movement jumps it was observed a significant 34.4% group average inhibition (p < 0.0001) at the first time point. This effect persisted for most of the participants for the next measurement (60 s after intervention) with an average reduction of 23.4% (p = 0.008). At the third measurement, 90 s after the procedure, the reflexes were on average still 21.4% smaller than baseline, although significant level was not reached (p = 0.053). From 120 s following the intervention, the reflex was fully recovered. This study suggests that not every type of muscle contraction promotes a prompt recovery of a stretch-induced inhibition of muscle spindle sensitivity.


Autologous bone marrow transplantation with 4-hydroperoxycyclophosphamide purging for acute myeloid leukaemia beyond first remission: a 10-year experience.
Between January 1987 and January 1997, 69 eligible patients with acute myeloid leukaemia (AML) in either second (CR2) or third (CR3) complete remission (CR2 = 60, CR3 = 9) underwent 4-hydroperoxycyclophosphamide-purged autologous bone marrow transplantation (BMT) at the Johns Hopkins Oncology Center. The patients' median age was 27 years (range 1-62) and all received busulphan and cyclophosphamide as their preparative regimen. The probability of event-free survival (EFS) at 5 years was 30% [95% Confidence Interval (CI): 19-42%] for CR2 patients and 22% (3-51%) for those in CR3, with a median follow up of 8 years in the surviving group. The median time to an absolute neutrophil count of 0.5 x 109/l was 45 d (range 20-185). Relapse was the major cause of failure with a relapse rate of 55% in CR2 and 44% in CR3, while the non-relapse, transplant-related mortality rate was 15% in CR2 and 33% in CR3. In univariate analysis, patient age, cytogenetics, white blood cell count at presentation, CR1 duration and the sensitivity of clonogeneic leukaemia (CFU-L) in the graft to 4HC were all prognostic for EFS. Using each of these significant variables in multivariate modelling, patient age and sensitivity of CFU-L to 4HC were determined to be predictors of EFS. 4HC-purged autologous BMT produced results similar to allogeneic BMT for AML patients beyond first remission.


Reversal effect of bufalin on multidrug resistance in human hepatocellular carcinoma BEL-7402/5-FU cells.
Multidrug resistance (MDR) is a major obstacle to chemotherapy in patients with hepatocellular carcinoma (HCC). To overcome MDR and improve chemotherapeutic efficacy, novel reversal agents with higher efficacy and lower toxicity are urgently needed for HCC. The present study was designed to examine the potential reversal activity of bufalin, a toxic ligand isolated from the traditional Chinese medicine 'Chansu' and to elucidate the possible related mechanisms. A multidrug-resistant HCC cell line, BEL-7402/5-FU, was used as the cell model. The working concentration of bufalin as an effective reversal agent, and the cell viability in the reversal experiments were determined by MTT assay. The effects of bufalin at a non-cytotoxic dose on cell cycle distribution, apoptosis and drug efflux pump activity were measured by flow cytometry. Qualitative observation of apoptosis was also carried out by confocal microscopy. Furthermore, the effects of bufalin on the expression of potential genes involved in MDR of BEL-7402/5-FU cells, including thymidylate synthase (TS), P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), B-cell lymphoma-extra large (Bcl-xL) and Bcl-2-associated X protein (Bax), were determined using real-time PCR and western blot analysis. The results showed that bufalin at a concentration of 1 nM enhanced the chemosensitivity of BEL-7402/5-FU cells to 5-FU with a reversal fold of 3.8 which was similar to that of 1 µM verapamil. Bufalin significantly arrested the cell cycle at the G₀/G₁ phase, induced apoptosis through an increase in the Bax/Bcl-xL ratio, inhibited drug efflux pump activity via downregulation of MRP1, and reduced the expression of TS in BEL-7402/5-FU cells. The present study revealed that bufalin effectively reversed MDR in BEL-7402/5-FU cells through multiple pathways. The combination of bufalin with cytotoxic drugs may serve as a promising strategy for the chemotherapy of HCC.


Divergent effects of oxygen therapy in four models of uncontrolled hemorrhagic shock.
Treatment with oxygen exerts beneficial effects and prolongs survival in hemorrhagic shock induced by controlled bleeding. We evaluated the effects of inhalation of 100% oxygen in four models of uncontrolled bleeding in rats: amputation of the tail, laceration of two branches of the ileocolic artery, incision of the spleen, and laceration of the lateral lobe of the liver. After tail amputation, oxygen caused a short and transient increase in mean arterial blood pressure (MABP; P < 0.01), decreased distal aorta (DA) blood flow by 27% (P < 0.01), and induced transient redistribution of blood flow to the superior mesenteric artery (SMA; P < 0.01). Later on, MABP in the oxygen group decreased gradually and was significantly lower than in air controls (P < 0.01). Oxygen therapy increased the mean blood loss by 40% (P < 0.01), increased blood lactate (P < 0.01), and shortened the survival time (P < 0.01). After laceration of two branches of the ileocolic artery, oxygen treatment caused a transient increase in MABP and redistribution of blood flow to the SMA that was followed by a comparable decrease in MABP, increase in vascular resistance, and decreased blood flow in the DA and SMA. In this model, oxygen did not affect bleeding volume, blood lactate, or survival. A similar transient regional hemodynamic effect was found when oxygen was administered after spleen or liver injury; however, in both models, oxygen maintained MABP at significantly higher values (P < 0.05). The results point to differential effects of oxygen in uncontrolled bleeding with benefits in bleeding from small parenchymal vessels and possible detrimental effect in bleeding from large size vessels.


Hydrogen sulfide: neurophysiology and neuropathology.
Hydrogen sulfide (H(2)S) was known to be a toxic gas and an environmental hazard for many decades. However, it is now recognized that H(2)S may serve as a gaseous mediator that is endogenously produced to influence biological functions in mammalian. Together with nitric oxide and carbon monoxide, it forms the group of mediators that has been termed the "gasotransmitters." The past decade has seen an exponential growth of scientific interest in the physiological and pathological significance of H(2)S especially with respect to its role in the central nervous system and the cardiovascular system. In the central nervous system, H(2)S facilitates long-term potentiation and regulates intracellular calcium concentration and pH level in brain cells. Intriguingly, H(2)S produces antioxidant, anti-inflammatory, and antiapoptotic effects that may have relevance to neurodegenerative disorders. Abnormal generation and metabolism of H(2)S have been reported in the pathogenesis of ischemic stroke, Alzheimer's disease, Parkinson's disease, and recurrent febrile seizure. Exogenously applied H(2)S is demonstrated to have value for the treatment of febrile seizure and Parkinson's disease. This article presents an overview of current knowledge of H(2)S in relation to brain functions, with a special emphasis on its neuroprotective effects and the underlying cellular and molecular mechanisms.


The brain prolactin system: involvement in stress response adaptations in lactation.
This review focuses on prolactin as a potential candidate for the regulation of emotional and neuroendocrine stress responses in the brain. In particular, we summarise evidence for a brain prolactin receptor-mediated anxiolytic action both in female and male rats, and for inhibitory actions on the reactivity of the hypothalamic-pituitary-adrenal (HPA) axis and the neurohypophysial oxytocin system. These physiological functions of the brain prolactin system are especially relevant in the peripartum period, as an attenuation of behavioural and neuroendocrine stress responses has been described during pregnancy and lactation. At this time, there is an increase in brain prolactin receptor expression and binding, and an increase in hypothalamic prolactin gene expression. In the absence of a selective prolactin receptor antagonist, complementary approaches including chronic intracerebral infusion of prolactin, and antisense targeting of the long form of the brain prolactin receptor were used to investigate the actions of prolactin. The hypothesis of a brain prolactin system activated in the peripartum period which contributes to the adaptive changes in stress responsiveness in order to support reproductive functions is strongly emphasised.


Low-temperature survival of Salmonella spp. in a model food system with natural microflora.
The United States Department of Agriculture requires chilled poultry carcass temperature to be below 4°C (40°F) to inhibit the growth of Salmonella and improve shelf life. Post-process temperature abuse of chicken leads to proliferation of existing bacteria, including Salmonella, which can lead to the increased risk of human infections. While models predicting Salmonella growth at abusive temperatures are developed using sterile media or chicken slurry, there are limited studies of Salmonella growth in the presence of background microflora at 4-10°C. Experiments in this study were conducted to determine the growth of Salmonella Typhimurium and Heidelberg at 4-10°C in brain heart infusion broth (BHI) and non-sterile chicken slurry (CS). Nalidixic acid-resistant Salmonella Typhimurium and S. Heidelberg (3 log CFU/mL) were inoculated separately in CS and sterile BHI in a 12-well microtiter plate and incubated at 4°C, 7°C, and 10°C, following which samples were taken every 24 h for up to 6 days. Samples from each well (n=5) were spread plated on XLT4 agar+nalidixic acid and incubated at 37°C for 24 h. Bacterial populations were reported as CFU/mL. No significant differences (p>0.05) were observed in the survival of both strains in CS and BHI over the period of 6 days at all temperatures except S. Heidelberg at 7°C. Survival populations of both strains at 4°C were significantly different (p ≤ 0.05) than at 7°C and 10°C in both media types. S. Heidelberg showed a maximum growth of 2 logs in BHI at 10°C among all the treatments. Growth patterns and survival of Salmonella at near refrigeration temperatures during carcass chilling can be useful to develop models to predict Salmonella growth post-processing and during storage, hence assisting processors in improving process controls.


[Anti-HBV effect of nucleotide analogues on mouse model of chronic HBV infection mediated by recombinant adeno-associated virus 8].
We evaluated the anti-HBV effects of nucleotide analogues, Entecavir (ETV) and Lamivudine (LAM) targeting mouse model of HBV persistent infection with recombinant adeno-associated virus 8 carrying 1.3 copies of HBV genome (rAAV8-1.3HBV). Ninety percent (27 of 30 mice) of rAAVS-treated mice were chosen as mouse model. Four groups were orally administrated with different doses of ETV (1 mg/(kgd) or 0.1 mg/(kgd)) and LAM (500 mg/(kgd) or 100 mg/(kgd)) once a day for 10 days. The other two groups were set as normal saline treated and untreated control. We detected the levels of HBV DNA, HBeAg and HBsAg in sera at different time. Results indicate that HBV DNA level decreased significantly (P < 0.05) in drug-treated groups compared with normal saline group after drug administration. Fifteen days after the drug withdrawal, HBV DNA level rebounded back obviously (P < 0.05) in groups with low doses of ETV and LAM. However, there was no apparent change of HBeAg and HBsAg in the whole process among all groups. These results showed that our model could reflect the anti-viral effect of nucleotide analogues. This model can be a useful and convenient tool for anti-HBV drug discovery.


Sleep-disordered breathing in alcoholics.
Sleep apnea and related disorders contribute to disturbed sleep in abstinent alcoholics. In an earlier report from our group, sleep-disordered breathing was common and increased with age in a cohort of 75 abstinent alcoholics. We now report an extension of the previous work that includes studies of an additional 103 abstinent alcoholics undergoing treatment for alcoholism (total sample = 188) and a comparison group of 87 normal subjects. The presence and severity of sleep-disordered breathing was assessed with polysomnography. Among the alcoholics, sleep-disordered breathing (defined as 10 or more apneas plus hypopneas per hour of sleep) was present in 3% of 91 subjects under age 40, 17% of 83 subjects age 40 to 59, and 50% of 14 subjects age 60 or over. Subjects with sleep-disordered breathing were more likely to be male and had more severe sleep disruption and nocturnal hypoxemia and more complaints related to daytime sleepiness than subjects without sleep-disordered breathing. In a multiple linear regression analysis, age and body mass index were significant predictors of the presence of sleep-disordered breathing, whereas smoking history and duration of heavy drinking were not predictors after controlling for the effects of age and body mass index. Our findings suggest that sleep-disordered breathing contributes significantly to sleep disturbance in a substantial proportion of older alcoholics and that symptomatic sleep-disordered breathing increases with age in alcoholics. Sleep-disordered breathing, when combined with existing cardiovascular risk factors, may contribute to adverse health consequences in alcoholics.


Do ancillary properties of antihypertensive drugs explain the outcome results of recent trials?
In a quantitative overview of published trials, we investigated whether some pharmacological properties of antihypertensive drugs, besides reduction in blood pressure, explain cardiovascular outcomes in hypertensive or high-risk patients. Across trials, using meta-regression, we correlated odds ratios with differences in systolic blood pressure between study groups. We then compared odds ratios of benefit observed in recent trials with those predicted by metaregression on the basis of the differences in systolic pressure between randomised groups. Significant differences in systolic pressure between randomised groups (experimental minus reference) were observed in the ALLHAT (-2/+1), CAPPP(-3/-1) and NORDIL (-3.1/+0.2) trials. Furthermore, the differences in achieved systolic and/or diastolic pressure between study groups were also significant in the hypertension trials which involved untreated control patients, as well as in MIDAS (-3.5/ approximately 0 mm Hg), HOPE (-3.3/-1.0 mm Hg), PART2 (-5/-4 mm Hg), and SCAT (4/-2 mm Hg) (1). The differences between the observed odds ratios and those predicted by the meta-regression between outcome and difference in systolic pressure did not reach statistical significance except for the NORDIL trial, in which the risk of stroke was lower on diltiazem than on the older drugs despite a 3.1 mm Hg higher systolic pressure on the calcium-channel blocker. The finding that in the reviewed trials blood pressure reduction largely accounted for outcome emphasizes the desirability of blood pressure control. The hypothesis that converting-enzyme inhibitors or alpha-blockers might influence cardiovascular prognosis over and beyond their antihypertensive effect remains unproved.


Temporary splenic artery occlusion during construction of the distal splenorenal shunt.
A technique for temporary occlusion of the splenic artery during construction of the distal splenorenal shunt is described. This maneuver is proposed to reduce intraoperative blood loss associated with mobilization of the splenic vein in the cirrhotic patient.


Unexpected findings from target analysis of immunoglobulin E and its receptor.
The membrane receptor for immunoglobulin E (IgE) and its ligand, IgE, were irradiated with high-energy electrons. Loss of binding activity was measured for each, and the size of the functional targets was assessed. In both cases, the target size was substantially smaller than the covalent structure of the molecule. The direction of this discrepancy is unprecedented on the basis of experience with loss of enzymatic activity by irradiation; indeed, two enzymes which were present in the receptor preparations gave expected values when measured simultaneously. We suggest that in instances where a function such as ligand binding resides in a conformationally stable domain, radiation inactivation may be capable of revealing this.


Small platinum cluster hydrides in the gas phase.
The reactions of small cationic platinum clusters (Pt2(+)-Pt7(+)) with molecular hydrogen were investigated, and the structures of the hydride complexes were analyzed using IR spectroscopy. We determined the relative reaction rates for the addition of the first H2 molecule to the platinum clusters, and we report the hydrogen saturation coverages observed at high H2 concentration. High H atom per Pt atom ratios were observed, similar to earlier measurements on other group-10 transition metals. The structures of the fully saturated complexes of Pt2(+)-Pt5(+) were investigated using a combination of infrared multiple-photon dissociation (IR-MPD) spectroscopy in the frequency range of 550-2050 cm(-1) and density functional theory-based calculations. We found molecularly bound hydrogen alongside bridge and often atop binding of hydrogen atoms for all of the low-energy structures, in contrast to earlier theoretical predictions.


Serum TSH and the response to radioiodine treatment of toxic multinodular goitre.
A retrospective analysis of data from 73 consecutive patients with toxic multinodular goitre treated with iodine-131 (131I) during a 2-year period was performed to investigate if serum TSH at the time of 131I treatment influences the outcome. The dose of 131I was calculated according to a model compensating for thyroid size estimated by palpation and 24-h 131I uptake. Serum TSH was determined by a third-generation assay with a functional sensitivity of 0.03 mU/l. A significantly more pronounced response to 131I treatment was observed in patients with TSH > 0.0 mU/l than in patients with TSH = 0.0 mU/l (P = 0.0006. This difference resulted in a threefold lower frequency of non-responders and a fivefold higher rate of early hypothyroidism in the group with detectable serum TSH. While the high frequency of hypothyroidism among patients with measurable serum TSH can be explained by destruction of normal thyroid tissue, the high frequency of treatment failure in the group with serum TSH = 0.0 mU/l suggests that autonomous thyroid tissue may also be sensitized to a deleterious effect of 131I through stimulation by TSH. We conclude that serum TSH has a significant influence on the outcome of 131I treatment of toxic multinodular goitre. The results of 131I treatment may be improved by adjustment of the dose of 131I according to the serum TSH level, in addition to adjustment for goitre size and 24-h 131I uptake.