Vasomodulatory effects of the angiotensin II type 1 receptor antagonist losartan on experimentally induced cerebral vasospasm after subarachnoid haemorrhage.
Cerebral vasospasm following subarachnoid haemorrhage (SAH) remains one of the major factors contributing to poor overall patient outcome. Prostaglandin F2-alpha (PGF2a) induces vasoconstriction. After SAH, PGF2a leads to cerebral inflammation and enhanced vasoconstriction, resulting in cerebral vasospasm. Losartan is already known to have beneficial effects in stroke models and also on several cerebral inflammatory processes. Therefore, the aim of the study was to analyse the effect of losartan on PGF2a-enhanced vasoconstriction after SAH. To investigate the effect of losartan on PGF2a-enhanced vasoconstriction after SAH, cerebral vasospasm was induced by a double-haemorrhage model. Rats were killed on day 3 and 5 after SAH followed by measurement of the isometric force of basilar artery ring segments in an organ bath. PGF2a induced a dose-dependent contraction. After pre-incubation with losartan, the maximum contraction (Emax) for sham-operated animals was significantly lowered [Emax 6% in losartan 3 × 10-4 molar (M) vs. 56% without losartan]. Also, after induced SAH, PGF2a induced no vasoconstriction in pre-incubated vessels with losartan 3 × 10-4 M on day 3 (d3) as well as on day 5 (d5). For the vasorelaxative investigations, vessel segments were pre-incubated with PFG2a. Cumulative application of losartan completely resolved the pre-contraction in sham-operated animals (non SAH: 95% relaxation). After SAH, losartan not only resolved the pre-contraction (d5: 103%), but also exceeded the pre-contraction (d3: 119%). Therefore, a statistically significantly increased and earlier relaxation was calculated for all losartan concentrations [Emax (d3/d5) and pD2 (d3/d5)] compared with the solvent control group. In a physiological and pathophysiological setup, losartan reduces a PGF2-induced vasoconstriction and reverses a PGF2a-precontraction completely. This fact can be integrated in pushing forward further concepts trying to antagonise/prevent cerebral vasospasm after SAH.


Impaired systemic ventricular relaxation affects postoperative short-term outcome in Fontan patients.
Systemic ventricular end-diastolic pressure has been used as a predictor of outcome in patients undergoing the Fontan operation. However, this index only evaluates late diastolic function and does not assess active ventricular relaxation during the phase of early diastole, a key component of systemic venous pathway flow. This study sought to examine whether impaired preoperative systemic ventricular relaxation, expressed as the time constant of isovolumic relaxation (tau), affects short-term postoperative outcome in Fontan patients. All patients who underwent Fontan operation between May 1998 and November 2001 were enrolled. Tau was calculated from digitized preoperative systemic ventricular pressure tracings. Standard preoperative invasive indices were also recorded and analyzed. These independent variables were then entered into a multiple stepwise regression model, with length of intensive care unit stay, length of hospital stay, and prolonged pleural effusion as outcome variables. Twenty-seven patients fulfilled inclusion criteria. Systemic left ventricle predominated, and all patients had undergone prior staged palliation. Extracardiac Fontan was the commonest operative technique. Of the independent variables examined, tau was the only statistically significant predictor of length of intensive care unit stay (P <.001) and length of hospital stay (P =.002). None of the independent variables predicted pleural effusion greater than 10 days. Tau was the only significant preoperative invasive predictor of short-term outcome in the Fontan patients. This illustrates the importance of systemic ventricular relaxation and highlights the need for a more comprehensive assessment of diastolic function before the Fontan operation.


[Stomach rupture following normo-frequent jet ventilation].
We report a case of a gastric rupture following jet ventilation during laryngoscopy.


[On key role of acupoints in elongated needle therapy].
To study on characteristics and application of key acupoints in Elongated Needle Therapy. Probe into method of determining key acupoints and their clinical application from characteristics of channels, characteristics of acupoints, position of diseases, pathogenesis, syndromes and other aspects. Establishment of the theory of key acupoints of enlongated needle therapy reflects the principle of "fewer but better" in acupoint selection of enlongated needle therapy, which can reduce pain of the patient and increase the therapeutic


A likelihood ratio-based approach for improved source attribution in microbiological forensic investigations.
A common objective in microbial forensic investigations is to identify the origin of a recovered pathogenic bacterium by DNA sequencing. However, there is currently no consensus about how degrees of belief in such origin hypotheses should be quantified, interpreted, and communicated to wider audiences. To fill this gap, we have developed a concept based on calculating probabilistic evidential values for microbial forensic hypotheses. The likelihood-ratio method underpinning this concept is widely used in other forensic fields, such as human DNA matching, where results are readily interpretable and have been successfully communicated in juridical hearings. The concept was applied to two case scenarios of interest in microbial forensics: (1) identifying source cultures among series of very similar cultures generated by parallel serial passage of the Tier 1 pathogen Francisella tularensis, and (2) finding the production facilities of strains isolated in a real disease outbreak caused by the human pathogen Listeria monocytogenes. Evidence values for the studied hypotheses were computed based on signatures derived from whole genome sequencing data, including deep-sequenced low-frequency variants and structural variants such as duplications and deletions acquired during serial passages. In the F. tularensis case study, we were able to correctly assign fictive evidence samples to the correct culture batches of origin on the basis of structural variant data. By setting up relevant hypotheses and using data on cultivated batch sources to define the reference populations under each hypothesis, evidential values could be calculated. The results show that extremely similar strains can be separated on the basis of amplified mutational patterns identified by high-throughput sequencing. In the L. monocytogenes scenario, analyses of whole genome sequence data conclusively assigned the clinical samples to specific sources of origin, and conclusions were formulated to facilitate communication of the findings. Taken together, these findings demonstrate the potential of using bacterial whole genome sequencing data, including data on both low frequency SNP signatures and structural variants, to calculate evidence values that facilitate interpretation and communication of the results. The concept could be applied in diverse scenarios, including both epidemiological and forensic source tracking of bacterial infectious disease outbreaks.


[The effects of elevated calcium concentrations in artificial cerebrospinal fluid on pial arteries during perivascular microperfusion and the Ca++-antagonistic effect of bencyclane (author's transl)].
The influence of artificial cerebrospinal fluid (CSF) containing 6, 9 and 18 mEq/l Ca++, respectively, on 145 pial arteries of nine anesthetized cats was investigated by the perivascular microperfusion technique. The higher the concentration of Ca++ in the perivascular space and the longer these high Ca++ concentrations acted on the vascular wall, the more pronounced were the constrictions of the arteries. If N-[3-(1-benzyl-cycloheptyloxy)-propyl]-N,N-dimethyl-amine (bencyclane-hydrogenfumarate, Fludilat) (10 mg/100 ml) was added to the CSF, dilatations occurred, even if the concentrations of Ca++ were higher than in normal CSF (3 meq/l). The degree of dilatation, however, was dependent on the Ca++ concentration in the CSF. With high Ca++ in the CSF the dilatatory action of bencyclane was inhibited when K+ and H+ in the CSF were kept constant. The reaction can be described as Ca++ antagonism, the possible mechanisms of which are discussed.


Cervical os obliteration after laser surgery in patients with amenorrhea.
Thirty-eight postmenopausal women and one with pituitary amenorrhea underwent cervical laser surgery. The cervical canal of each patient was patent 2 weeks later. Eighteen of the 30 women reevaluated 4-48 months later had total obliteration of the cervical canal. In some patients, the cervix was obliterated and flush with the vaginal vault so that it could not be identified. Five other patients had severe cervical stenosis. Factors contributing to cervical os obliteration appeared to be the depth of the cervical defect, the lack of the physical action of blood passing through the cervical canal, and the hypoestrogenic state. This outcome makes continued adequate cytologic and colposcopic surveillance of these patients impossible and leaves them at risk for developing unrecognized cervical and endometrial disease.


The Rieske/cytochrome b complex of Heliobacteria.
Heliobacteria have a Rieske/cytochrome b complex composed of a Rieske protein, a cytochrome b(6,) a subunit IV and a di-heme cytochrome c. The overall structure of the complex seems close to the b(6)f complex from cyanobacteria and chloroplasts to the exception of the di-heme cytochrome. We show here by biochemical and biophysical studies that a heme c(i) is covalently attached to the Rieske/cytochrome b complex from Heliobacteria. We studied the EPR signature of this heme in two different species, Heliobacterium modesticaldum and Heliobacillus mobilis. In contrast to the case of b(6)f complex, a strong axial ligand to the heme is present, most probably a protonatable amino acid residue.


Short-term in-vitro culture and cryopreservation of spermatogenic cells used for human in-vitro conception.
Testicular cell suspensions were prepared from obstructive and non-obstructive azoospermic men and were cultured in vitro for 96 h as (i) mixed cell populations and (ii) isolated homogeneous populations of primary spermatocytes, round spermatids and elongating spermatids. The cells lost their viability gradually during the first 24 h period. By 72 h almost 90% of the cells were non-viable. Isolated pure fractions showed better viability at each time interval (P < 0.0005). Throughout the culture period primary spermatocytes, elongating spermatids and other non-spermatogenic cells showed no change in their morphology, but almost 22% of round spermatids showed growth of flagella. Most of the round spermatids developed their flagella during the first 4-8 h period of culture. Isolated pure round spermatids showed better flagellar growth compared with mixed cell suspensions (P < 0.0005). The spermatogenic cells were successfully cryopreserved. However, when mixed spermatogenic cell suspensions were cryopreserved, more cells lost their viability compared with when isolated pure fractions were cryopreserved (P < 0.0005).


[Study of optokinetic nystagmus and spino-motor functions with cyclo-rotatory optokinetic stimulus].
It has been shown that the neural channels from the otolith organs and the vertical semicircular canals connect to the cyclo-rotatory oculomotor system. However, only a few studies have been conducted to examine the relationship between the cyclo-rotatory optokinetic (COK) and the vestibular inputs. Accordingly, we have analyzed the cyclo-rotatory oculomotor output evoked by a COK stimulus, in 30 subjects; 21 normal adults, 4 elderly persons, and 5 persons with unilateral vestibular dysfunction. In addition, the spinal motor output was simultaneously recorded and comparatively analyzed. The increase in COK nystagmus (COKN) was less than that in horizontal and vertical OKN. There was a significant decline in the maximum slow phase eye velocity in the elderly subjects as well as in the subjects with unilateral vestibular dysfunction, compared to that in the normal adult subjects. Regarding the spinal motor output, in the subjects with unilateral vestibular dysfunction, a pronouned increase in the sway distance from the center of gravity was found with COK stimulus forward the lesioned side. However, with the COK stimulus, there was no significant correlation between the output functions of the cyclorotatory oculomotor system and those of the spinal motor system.


A new colorimetric breath indicator (Colibri). A comparison of the performance of two carbon dioxide indicators.
Colorimetric carbon dioxide indicators are designed for the verification of satisfactory tracheal tube placement. However, widespread use of the device in this and other applications is hampered by limitations in its performance characteristics. A new colorimetric breath indicator (Colibri) has been developed that overcomes major shortcomings of current technology. A simple method is described that can be used to evaluate the properties of colorimetric carbon dioxide indicators in a quantitative way.


Mindful caring: using mindfulness-based cognitive therapy with caregivers of cancer survivors.
Caregivers of cancer survivors face many burdens that often require treatment by mental health professionals. One intervention, mindfulness-based cognitive therapy, aims to help individuals change the ways in which they relate to their thoughts rather than changing their thoughts. In this manuscript, we discuss the use and adaption of mindfulness-based cognitive therapy with caregivers of cancer survivors as a way to decrease caregiver burden and increase caregiver quality of life. A session-by-session breakdown of how to tailor mindfulness-based cognitive therapy to caregivers of cancer survivors is provided.


A simple therapeutic combination for type 2 diabetes.
When oral agents alone can no longer provide adequate glycemic control, the combination of a single bedtime injection of insulin with two daily doses of metformin will often normalize blood glucoses levels without the weight gain and hypoglycemia that may occur with other combined regimens.


Functional responses of tumor cells to phorbol esters: role for prostaglandins.
The effects of phorbol esters on five murine cell lines were examined. In three of these lines, all of which were highly malignant, phorbol ester treatment induced motility and foreign surface adherence while concomitantly inhibiting proliferation. In two other, nonmalignant cell lines phorbol ester treatment stimulated proliferation but did not influence motility or adherence. Possible roles for prostaglandins in these responses were investigated. The mitogenic effects of the phorbol esters were duplicated by prostaglandin F2 alpha. In contrast, prostaglandin E1 and prostacyclin inhibited proliferation induced by the phorbol esters. These agents also inhibited phorbol ester-induced cell motility.


Acute and chronic effects of the dihydropyridine calcium antagonist nisoldipine on the resting and exercise hemodynamics, neurohumoral parameters, and functional capacity of patients with chronic heart failure.
The acute and chronic effects of the dihydropyridine calcium antagonist nisoldipine were studied in patients with chronic heart failure (LV EF < .35; peak VO2 < 25 ml/kg/min) caused by idiopathic or postinfarction cardiomyopathy. The study group initially consisted of 16 patients; two patients were excluded from the acute study due to side effects of the drug and two more patients were excluded during the chronic part of the study because of excessive tachycardia or worsening heart failure, respectively; therefore, the final study group consisted of 12 patients. Each patient was evaluated at rest, in the supine and sitting positions, and during maximal bicycle exercise, before and after acute and chronic (2-3 months) oral nisoldipine therapy (20 mg bid). Plasma levels of renin activity, aldosterone, norepinephrine, and epinephrine were measured before and 1 hour after nisoldipine in 10 patients. Concomitant therapy with digitalis and diuretics was kept constant throughout the study. At rest, in the supine position, nisoldipine (20 mg orally) induced an acute increase of cardiac index from 2.87 +/- 0.52 to 3.93 +/- 1.52 l/min/m2, with a reduction of mean arterial pressure from 97 +/- 7 to 85 +/- 9 mmHg and systemic vascular resistance from 1417 +/- 201 to 968 +/- 257 dynes sec/sec cm5 without significant changes of right atrial and pulmonary pressures. Hemodynamic effects peaked 1 hour after its administration and persisted for 6 hours. Similar changes were observed in the resting sitting position.(ABSTRACT TRUNCATED AT 250 WORDS)


Chemical modification and hybrid enzyme formation as probes of the active site and subunit interactions in Escherichia coli succinyl-CoA synthetase.
Succinyl-CoA synthetase from Escherichia coli has an alpha 2 beta 2 subunit structure and is known to display half-of-the-sites reactivity with respect to its phosphorylation by ATP. The studies reported herein are a component of our attempts to rationalize the heterologous tetrameric structure in terms of catalytic function. The isolated refolded beta subunit interacts specifically with an affinity column of agarose-hexane-CoA, consistent with the idea that the CoA-binding subsite of the active center is located on the beta subunit. The enzyme is inactivated by phenylglyoxal according to biphasic kinetics; saturating levels of the substrates CoA and ATP, alone or in combination, give only partial protection against such inactivation. Treatment of the enzyme with the sulfhydryl reagent 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) resulted in rapid inactivation, accompanied by the reaction of three to four-SH groups per molecule; prolonged incubation with NBD-Cl eventually results in reaction of 16 of the 24 sulfhydryl groups of the tetramer. Hybrid enzyme preparations have been constructed by refolding mixtures containing beta and various ratios of native and NBD-Cl-modified alpha subunits. The loss of activity associated with the incorporation of chemically modified alpha is not that predicted by a simple model based on binomial distribution, but is complex and consistent with the kind of intersubunit communication that may be expected for catalytic cooperativity between the two active sites of the enzyme molecule.


[Genetic and phenogenetic study of the ts-mutant group of Pseudomonas aeruginosa PA01 phage phi KZ].
A group of ts mutants of phi KZ phage specific for Pseudomonas aeruginosa was isolated and studied. A phi KZ phage particle has a unique feature: a specific structure as an internal body concerned with DNA packaging which is present in the phage capsid. Ts mutants were distributed into complementation groups. The time of the development block when grown at elevated temperatures was determined for mutants from several groups, the exact stage of the block having been defined for some late ts mutants. As was found for ts759, the stage of connection of heads containing DNA and the inner body with tails was blocked. The results obtained with ts759 allowed to prove the circular location of fibrous material (DNA?) around the inner body. The conditions for phage crosses were revealed. The genetic map of phi KZ is circular. It may be concluded, considering the linear phi KZ DNA structure in capsids, that circular permutations of phage DNA take place during phage maturation or DNA packaging.


[Drugs in veterinary medicine. The role of the veterinary drug industry].
Veterinary medicines constitute an unescapable element in the scheme of animal health and welfare. Nowadays, they are used more and more to improve health and productivity in farm animals. When a veterinary medicine is prescribed it must not only be effective but must also be safe for both animals and humans. Due to ever changing regulations and constant improvements in residue detection techniques it is necessary to conduct new investigations with existing products. It therefore costs a great deal of time and money to introduce, and maintain, a product in the market. In future, therefore, fewer medicines with more limited indications will be introduced and these will be to combat important production disorders in the more significant species only. In view of the above, research and production will be restricted to large, international, concerns. Due to our well structured agricultural industry and the existence of well organized and equipped veterinary research institutions, and practitioners, Holland is able to play an important role in the development of veterinary medicines. Close co-operation between all involved parties coupled with an efficient registration procedure is not ony of benefit to the veterinary pharmaceutical industry but also for international recognition of our national animal husbandry industry, ancillary industries and veterinary and other consultants. In this scheme of things the accent is not upon qualifications but upon the skills of veterinarians - wherever placed - who are involved in the administration of veterinary medicines.


Pharmacokinetic modeling of the anticonvulsant response of oxazepam in rats using the pentylenetetrazol threshold concentration as pharmacodynamic measure.
This investigation developed strategies along which the anticonvulsant effect of oxazepam in the rat could be pharmacokinetically modeled. After determination of the pharmacokinetics of oxazepam, which could be described with a two-compartment model (half-lives of distribution and elimination 6 and 52 min, respectively), the drug was administered iv to groups of animals to achieve a serum concentration range of 0.1-2.5 mg/L at 10, 45, and 120 min after administration. At these time points pentylenetetrazol (PTZ) was infused slowly until the first myoclonic jerk occurred. The anticonvulsant response, expressed as the elevation of the serum or brain threshold concentration of PTZ, was modeled versus the serum (both total and free) and brain oxazepam concentration, according to the sigmoid Emax model. The total serum and brain oxazepam EC50 values are about 0.5 mg/L and 1.1 mg/kg, respectively, and Emax 120 mg/L PTZ. No marked differences in pharmacodynamic parameters between the three time groups were found, which indicates that serum and brain are pharmacokinetically indistinguishable from the effect compartment, that there is no (inter)activity of oxazepam metabolites and absence of development of acute tolerance during the investigated time frame. An interfering role of metabolites was also excluded by a direct radioreceptor assay of oxazepam, yielding very similar results as the specific chromatographic assay. It is concluded that the conception-anticonvulsant effect relationship of oxazepam can satisfactorily be described by the sigmoid Emax model, when utilizing the employed experimental strategies.


[Characteristics of communication of schizophrenic, neurotic, and healthy adolescents].
Research on communication skills in psychotic patients demonstrates that in dialogues schizophrenics neglect the needs of the listener. There are only few linguistic studies which investigate the speech of schizophrenic children and adolescents. The verbal and non-verbal communication of schizophrenic, neurotic, and healthy adolescents during a problem solving situation was transcribed and compared by a content analysis. The transcripts were screened for dialogue control and communication disturbance of verbal/non-verbal activities of the speaker and listener: Dialogue control was defined by the variables signals of the speaker or signals of hearer and eye or body contact of the test person to the experimenter. Communication disturbance was defined as the amount of incomprehensible articulation and selections. Neurotic test persons produce the highest signals of speaker rate. In dialogues with neurotic and schizophrenic test persons the experimenter uses more signals of hearer than in dialogues with healthy test persons. In dialogues with neurotic test persons the experimenter shows more signals of the speaker than in dialogues with healthy test persons. Schizophrenics neglect more often the statements of the experimenter than in other dialogues and vice versa. Although the experimenter was instructed to restricted verbal behavior the communication intensified in the neurotic group. The communication in the schizophrenic group was characterized by frequent communication disturbance.


Predictors of CBT-pretreatment intervention engagement and completion: Evidence for peer support.
Mental illness is a major public health concern negatively affecting persons across multiple domains. To address this, health care systems have prioritized access to care and use of empirically supported treatments to better serve those with psychiatric concerns. Rates of dropout from psychotherapy are high, especially in routine clinical settings. Peer support has been promulgated as fostering treatment engagement and completion due to a connection forged from common experience (e.g., military service, psychiatric diagnosis, etc.). As such, the Veterans Health Administration has invested heavily in peer support, although there is limited direct evidence that it enhances treatment engagement or completion. The current study advances upon prior research, showing positive effects of a Cognitive Behavioral Therapy-Pretreatment Intervention (CBT-PTI) on individual therapy outcomes (Lusk, Lyubkin, Chermack, Sanborn, & Bowersox, 2016), by comparing CBT-PTI initial engagement and completion among 352 veterans who met with either a Peer Support Specialist or a Program Support Assistant. Logistic regressions were used to assess the effects of significant unadjusted predictors on CBT-PTI initial engagement and completion, and Mann-Whitney tests were used to further describe differences between veterans who met with PSA versus PSS. Support for the role of PSS was found for CBT-PTI completion, and there was a trend for engagement, although further research is needed. This study provides preliminary support for the use of PSS in fostering CBT-PTIs in routine clinical settings, although further study is warranted to confirm and expand support. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


[Effect of nanosize delivery system for ASODN against hTERT on the expression of telomerase in the esophageal cancer EC9706 cells].
To investigate the inhibitory effect of nanoparticle-mediated antisense oligodeoxynucleotide (ASODN) of human telomerase reverse transcriptase (hTERT) on telomerase in the esophageal cancer EC9706 cells. Line-polyethylenimine (L-PEI) was used to condense ASODN into nanoparticle and to couple NGR peptides into targeting nanoparticle, and the prepared L-PEI/ASODN complexes were transfected into the EC9706 cells. Cellular uptake of L-PEI/ASODN complexes was detected by laser confocal scanning microscopy. MTT assay was used to detect the inhibitory rate of EC9706 cell growth. The level of hTERT mRNA and its protein expression were measured by RT-PCR and immunohistochemistry, respectively. Annexin V FITC/PI double labeling was used to detect cell apoptosis. The distribution of drug in nude mice was observed by laser confocal scanning microscopy, and the growth and morphology of the tumor was examined. The L-PEI-mediated ASODN uptake was enhanced. After transfection, the inhibitory rate of EC9706 cells was time-dependant and there was a significant difference between control cell group and L-PEI/ASODN group (P < 0.05). At 48 h after transfection, the level of hTERT mRNA was decreased significantly compared with that of control cell group (P < 0.05), and the expression of hTERT protein was negative. There was apparent apoptosis in EC9706 cells after transfection with L-PEI/ASODN complexes. For the two NGR/L-PEI/ASODN groups, fluorescence was observed in the liver, kidney, lung and tumor tissues of nude mice, and their uptake intensity was time-dependent. The mean volume of tumors in the two NGR/L-PEI/ASODN groups was significantly smaller than those in blank control group and SODN group (P < 0.05). Apoptotic bodies were detected in the tumors of L-PEI/ASODN group. The NGR/L-PEI/ASODN nanoparticles can effectively reach into the human esophageal cancer xenograft and inhibit the tumor growth in nude mice, and this may provide a theoretical and experimental basis for gene therapy for human esophageal squamous cell carcinoma.


Adhesive bonding of noble metal alloys with a triazine dithiol derivative primer and an adhesive resin.
The purpose of this study was to evaluate the bond strength and durability of a metal adhesive system bonded to noble metal alloys. Disc specimens were cast from type IV gold (type IV, Casting Gold M. C., metal-ceramic gold (Au-Pt-Pd, Degudent Universal, metal-ceramic palladium (Pd-Ga-Co, PTM 88 silver-indium (Ag-In-Zn, Salivan Hard and silver-palladium-copper-gold (Ag-Pd-Cu, S12) alloys and pure silver (pure Ag). The specimens were air-abraded with 50 micron alumina, conditioned with a thiol-based primer designed for noble alloys (V-Primer), and then bonded with an adhesive resin (Super-Bond Opaque Ivory). Shear bond strengths were determined after repeated thermocycling (4-60 degrees C, 1 min each, 100 000 cycles). The average bond strengths in MPa (n=8) were 30.9 for the type IV alloy, 29.0 for the Ag-Pd-Cu alloy, 28.0 for the Au-Pt-Pd alloy, 26.3 for the pure Ag, 26.0 for the Pd-Ga-Co alloy and 9.3 for the Ag-In-Zn alloy. The Ag-In-Zn alloy exhibited significantly lower bond strength than the other alloys, whereas the bond strengths of the other four alloys and pure Ag were comparable (P<0.05). It is concluded that the combined use of the thiol derivative primer and the adhesive resin is effective for bonding the noble metal alloys examined, with the exception of the Ag-In-Zn alloy.


Water quality assessment and modeling of an effluent-dominated stream, the Notwane River, Botswana.
In an effort to assess current and future water quality of the only perennial river in southeastern Botswana, this study presents water quality monitoring and modeling results for the effluent-dependent Notwane River. The water quality along the Notwane River, pre- and post-implementation of secondary wastewater treatment, was compared and results demonstrated that water quality improved after the new wastewater treatment plant (WWTP) went online. However, stream standards for chemical oxygen demand, total dissolved phosphorous, and fecal coliform were exceeded in most locations and the critical dissolved oxygen (DO) reached concentrations of less than 4 mg L(-1). High dissolved P concentrations and intense macrophyte growth at the impounding ponds and at sites within 30 km of the effluent waste stream confluence suggest that eutrophication was a function of P release from the ponds. Results of DO modeling demonstrated that an unpolluted inflow at approximately 10 km downstream of the confluence was responsible for raising DO concentrations by 2.3 mg L(-1), while SOD was responsible for a decline in DO concentrations of 1.4 mg L(-1) at 6 km downstream of the confluence. Simulations also showed higher DO concentrations during winter months, when water temperatures were lower. Simulations, in which the distributed biochemical oxygen demand (BOD) loading from cattle excrement was decreased, produced nominal increases in DO concentrations. An increase in WWTP BOD loadings to projected 2020 values resulted in a 1.3 mg L(-1) decrease in the critical DO concentration. Furthermore, a decrease in treatment plant efficiency, from 94% to 70% BOD removal, produced critical DO concentrations and anoxia along much of the modeled reach. This has significant implications for Gaborone, especially if decreased WWTP efficiency occurs as a result of the expected future increase in pollutant loadings.


Ribosomal initiation complexes probed by toeprinting and effect of trans-acting translational regulators in bacteria.
Toeprinting was developed to study the formation of ribosomal initiation complexes in bacteria. This approach, based on the inhibition of reverse transcriptase elongation, was used to monitor the effect of ribosomal components and translational factors on the formation of the active ribosomal initiation complex. Moreover, this method offers an easy way to study in vitro how mRNA conformational changes alter ribosome binding at the initiation site. These changes can be induced either by environmental cues (temperature, ion concentration), or by the binding of metabolites, regulatory proteins, and trans-acting RNAs. An experimental guide is given to follow the different steps of the formation of ribosomal initiation complexes in Escherichia coli and Staphylococcus aureus, and to monitor the mechanism of action of several regulators on translation initiation in vitro. Protocols to prepare the ribosome and the subunits are also given for Thermus thermophilus, Staphylococcus aureus, and Escherichia coli.


A randomized, prospective, double-blind, placebo-controlled evaluation of the effect of sedation on diagnostic validity of cervical facet joint pain.
Based on responses to controlled diagnostic blocks of cervical facet joints, the prevalence of cervical facet joint pain in chronic neck pain has been shown to range from 54% to 67%, with false-positive results of 27% to 63% with a single diagnostic block. Other confounding factors claimed to influence the diagnostic validity of cervical facet joint blocks include administration of anxiolytics and narcotics prior to or during the procedure. To evaluate the effect of midazolam and fentanyl on the validity of diagnosis of cervical facet joint pain. Randomized, prospective, double-blind, placebo-controlled evaluation. The study was undertaken in an interventional pain management practice. The design consisted of a placebo group receiving sodium chloride solution and two experimental groups receiving either midazolam or fentanyl. The patients included in the study were treated in the past and were presenting for repeat treatment after a significant period of symptom relief. Outcomes were assessed at baseline and after the administration of 1 of the 3 solutions (Group I, sodium chloride solution; Group II, midazolam; or Group III, fentanyl). Outcome measures included numeric pain scale, proportion of pain relief, and ability to perform prior painful movements. Pain relief of > or = 80% was noted in 5% of the patients in Group I, 8% in Group II, and 8% in Group III. However, > or = 50% relief was noted in 8% of the patients in Group I, 13% in Group II, and 27% in Group III. Overall, 8% of the patients in Group I, 13% in Group II, and 27% in Group III were able to perform movements which were painful prior to injection. The administration of sedation with midazolam or fentanyl is a confounding factor in the diagnosis of cervical facet joint pain in patients with chronic neck pain. However, if > or = 80% pain relief with ability to perform prior painful movements is used as the standard for evaluating the effect of controlled local anesthetic blocks, the diagnostic validity of cervical facet joint nerve blocks may be preserved.


Bifidobacterium moukalabense sp. nov., isolated from the faeces of wild west lowland gorilla (Gorilla gorilla gorilla).
Gram-staining-positive anaerobic rods were isolated from the faeces of a wild lowland gorilla (Gorilla gorilla gorilla) in Moukalaba-Doudou National Park, Gabon, and strain GG01(T) was taxonomically investigated. Based on phylogenetic analyses and specific phenotypic characteristics, the strain belonged to the genus Bifidobacterium. Phylogenetic analysis of its 16S rRNA gene sequence revealed that strain GG01(T) formed a single monophyletic cluster and had a distinct line of descent. Based on 16S rRNA gene sequence similarity, the type strains of Bifidobacterium catenulatum JCM 1194(T) (98.3%) and Bifidobacterium pseudocatenulatum (98.1%) JCM 1200(T) were the most closely related to this novel strain, although it was clear that they belonged to different species. hsp60 sequences also supported these relationships. The DNA G+C content of this novel strain was 60.1 mol%. Bifidobacterium moukalabense sp. nov. (type strain GG01(T) = JCM 18751(T) = DSM 27321(T)) is proposed.


Postoperative pyothorax.
Twenty-five cases of pyothorax occurred in a series of 1281 thoracotomies. Almost all cases of pyothorax without bronchopleural fistula were successfully treated by closed drainage and irrigation alone. On the other hand, patients with pyothorax and fistula who were treated only with closed drainage almost all had a poor outcome. When pyothorax with fistula was treated by closed drainage and irrigation followed by further procedures such as open window thoracostomy, muscle plombage and/or omentopexy, treatment was successful. It is concluded that pyothorax without fistula may be cured by closed drainage and irrigation alone, but that pyothorax with fistula requires operative intervention such as open window thoracostomy or omental flap as soon as possible.


Promoting self-determination of students who are deaf or hard of hearing.
Self-determination is a combination of attitudes, knowledge, and skills that enables individuals to make choices and engage in goal-directed, self-regulated behavior. Research in special education has demonstrated the benefits of promoting self-determination in achieving positive adult outcomes. However, to date, very little has been written about self-determination as it relates to the education of students who are deaf or hard of hearing. This article provides an overview of self-determination, suggestions for instructional planning, and guidance on resources that can be used to gather additional information.


[Statistical spectral study of alpha rhythms: modifications due to the tardive action of a hypnotic (author's transl)].
In a simple blind study to evaluate electroencephalographic criteria objectively, and to continue characterization of psychotropic compounds, 5 mg of nitrazepam, a hypnotic derivative, was given to seven subjects the night before the recording. We noted that in most subjects there was a reduction in the spectral intensity of the alpha rhythm, associated with a greater frequency instability, several hours after the absorption of nitrazepam. This corresponds to the tardive hypnotic action of the psychotrope, the importance of which is wellknown at the present time. In the same way as the increase in rapid rhythms, the slipping of 0.5 c/s of the dominant alpha frequency to the top could be characteristic of the action of nitrazepam.


Endovascular repair for aorto-enteric fistula: a bridge too far or a bridge to surgery?
To review our experience of endovascular treatment of aorto-enteric fistula (AEF). Between March 1999 and March 2005, 15 patients in five university and teaching hospitals in Belgium and The Netherlands were treated for AEF by endovascular repair. Twelve (80%) were male. The mean age was 67 years. Thirteen (87%) had had previous aortic or iliac surgery, 1.7-307 months before. All patients showed clinical or biochemical signs of bleeding. Eight (53%) were in shock, five (33%) had systemic signs of infection. Eight (53%) patients were treated in an emergency setting. Ten (67%) were treated with an aortouniiliac device, three (20%) with an aortobiiliac device, one with a tube graft and one with occluders only. All patients received antibiotics postoperatively for a prolonged period of time. All AEF were successfully sealed, the 30-days mortality was nil. Mean hospital stay was 20 (2-81) days. One patient died 2.7 months later of postoperative complications, one died of lung cancer. Until now, there are no signs of reinfection in four (27%) patients (mean follow-up 15.7 (1-44) months). However, reinfection or recurrent AEF occurred in nine (60%) patients after 9.5 (0.61-31) months. Seven patients were reoperated successfully, two patients died after reintervention. Endovascular sealing of AEF is a promising technique, which provides time to treat shock, local and systemic infection, and co-morbidity. This creates a better situation to perform open repair in the future with possibly better outcome. Danger of reinfection remains high. Endovascular sealing of AEF should, therefore, be seen as a bridge to open surgery when possible.


The effect of alpha-lactalbumin and beta-lactoglobulin hydrolysates on the metabolic activity of Escherichia coli JM103.
Bovine milk proteins alpha-lactalbumin (alpha-la) and beta-lactoglobulin (beta-lg) were hydrolysed with seven different proteolytic enzymes, and the effect of various hydrolysates on a genetically modified luminous Escherichia coli JM103 was tested in vitro with a bioluminescence assay for bacterial growth and metabolism. Undigested proteins did not inhibit the activity of tested E. coli JM103 at a concentration as high as 0.1 g ml-1. At the same concentrations, alpha-la hydrolysed with pepsin or trypsin and beta-lg hydrolysed with alcalase, pepsin or trypsin, showed a lower metabolic activity during the first 8 h of growth. The activity of E. coli JM103 in the presence of 25 mg ml-1 alpha-la or beta-lg hydrolysed with pepsin and trypsin was only 21% of the control after incubation for 6 h. The preliminary results indicated that ultrafiltration through 10 kDa and 1 kDa molecular mass cut-off membranes may be used to enrich bacteriostatic properties.


Identification of novel genes expressed in hypoxic brain condition by fluorescence differential display.
Fluorescence differential display (FDD) and comparative RT-PCR have been used extensively to detect differentially expressed genes. We investigated hypoxia-induced gene expression in the brain by FDD-PCR and comparative RT-PCR. Mice were anaesthetized after which hypoxia was induced by neck ligation for 1 min or 25 min, then were killed by decapitation, and the brains were dissected either immediately or 30 min after death (Group A1-0, Group A25-0, Group A1-30 and Group A25-30). Control mice without ligation of the neck were killed by decapitation under anaesthesia immediately (Group C-0) or 30 min after death (Group C-30). FDD-PCR, sequence analysis and comparative RT-PCR revealed that mitochondrial thymidine kinase 2, Rab6, selenoprotein T and two novel cDNAs were enhanced in Group A25-0 and Group A25-30 compared with the other groups. In Group A25-30, only RAP2 interacting protein and another novel cDNA were induced. In Group A25-0, one novel gene was detected. These findings were consistent with the results of statistical analysis by ANOVA. No differences of band pattern were observed among Groups A1-0, A1-30, C-0 and C-30. The genes exhibiting altered expression were associated with vital cellular functions, e.g., intracellular signaling and mitochondrial metabolism. In addition, we identified four novel genes, expressed after extended hypoxic conditions in mouse brain with suffocation. These results may contribute to clarify the pathophysiology of asphyxia in the brain and aid in the diagnosis of suffocation.


Sheehan's syndrome presenting with hypothyroidism and hypo-adrenalism despite treatment with thyroxine and prednisone.
A 35-year-old patient with Sheehan's syndrome presented with hypothyroidism and hypo-adrenalism despite having received treatment with regular daily L-thyroxine (0,3 mg) and prednisone (30 mg) for the preceding 12 months. Replacement of the prednisone with 37,5 mg cortisone acetate resulted in satisfactory control of the disease. The observations suggest that large doses of prednisone may interfere with thyroxine treatment.


Complications associated with the surgical treatment of prostatic abscessation.
Prostatic abscessation in the dog is a disease process in which diagnostic, therapeutic, and postoperative problems are frequently encountered. Several surgical techniques for the treatment of prostatic abscessation in the dog have been reported. However, few studies have described the indications for use of a particular technique or associated postoperative complications.


Thymosin alpha1 suppresses proliferation and induces apoptosis in human leukemia cell lines.
Thymosin alpha1 (Talpha1), a 28-amino acid peptide, is a well-known immune system enhancer for the treatment of various diseases. In the present investigation, the effects of Talpha1 on the proliferation and apoptosis of human leukemia cell lines (HL-60, K562 and K562/ADM) were studied. The proliferation was significantly depressed after 96 h of treatment with Talpha1, and obvious signs of apoptosis, i.e., cell morphology, nuclei condensation and Annexin V binding, were observed thereafter. Moreover, the up-regulation of Fas/Apol (CD95) and decrease in bcl-2 anti-apoptotic gene expression were observed in apoptotic cells. The expression and the function of P-glycoprotein (P-gp) can be slightly inhibited by Talpha1. It is noteworthy that K562 and K562/ADM were more sensitive than HL-60 cells when subjected to Talpha1. Furthermore, HepG-2, the human hepatoma cell line, displayed significant less sensitivity to Talpha1 than all the human leukemia cell lines. D-Tubocurarine (TUB), a nicotinic acetylcholine receptors (nAChRs) antagonist, significantly antagonized the inhibition effects induced by Talpha1, whereas atropine, a muscarinic acetylcholine receptor antagonist, did not exhibit such effects. All the results indicate that Talpha1 was able to significantly suppress proliferation and induce apoptosis in human leukemia cell lines.


Ultrasonic attenuation estimation in-vivo using the difference ratio correction method.
In recent years, B scanners have been widely used clinically. Obviously, it is of particular importance to use the commercial B scanners to characterize tissue by estimating its ultrasonic attenuation in vivo. However, there are a lot of difficulties in doing so because the output of a B scanner is affected by many unknown factors. In this paper, a time domain method named the difference ratio correction (DRC) method is proposed to estimate the ultrasonic attenuation of tissue in vivo. In this method, three tissue-mimicking phantoms with known acoustical properties were employed to eliminate the instrumentation errors of the B scanner and the measuring system and to correct beam diffraction for correct attenuation estimation. Other advantages of this method are that it is very convenient to apply this method clinically and there is no need to change the inner construction of the B scanner because this method only utilizes the video output. Experimental and clinical results have proved the validity of this method.


Clinicopathologic features and treatment of residual early cancers after endoscopic mucosal resection of the stomach.
We sometimes encounter residual or recurrent cancers after endoscopic mucosal resection (EMR) for early gastric cancer. The aim of the present study was to clarify the clinicopathologic characteristics of and optimal treatment for the residual cancers after EMR. Seventy-four patients with early gastric cancer were treated with EMR between 1994 and 2004. These patients were divided into 2 groups as follows: the curative group (n=59) and the noncurative group (n=15). The clinicopathologic data were compared between the 2 groups and the outcomes of additional therapy were reviewed. In the noncurative group, the tumors were located significantly frequently on the upper or middle third of the stomach compared with the curative group (P<0.05). The number of fragments in EMR was significantly larger in the noncurative group than in the curative group (P<0.05). Fifteen patients required additional treatment because of the residual cancer. Nine (75%) of 12 patients requiring surgery underwent laparoscopic surgery. Three patients were treated by endoscopic therapy. EMR with a single fragment and with a sufficient margin is useful for the complete resection of early gastric cancer. When residual cancer occurs, laparoscopic gastrectomy may be a good alternative.


Antitumor effect of adriamycin-encapsulated nanoparticles of poly(DL-lactide-co-glycolide)-grafted dextran.
In this study, we prepared adriamycin (ADR)-encapsulated core-shell type nanoparticles of a poly(DL-lactide-co-glycolide) (PLGA) grafted-dextran (DexLG) copolymer and evaluated its antitumor activity in vitro and in vivo. The particle size of ADR-encapsulated DexLG nanoparticles was around 50-200 nm and the morphology was spherical shapes at transmission electron microscopy (TEM) observation. Since reconstitution of lyophilized nanoparticles is essential to practical use in vivo, ADR-encapsulated DexLG nanoparticles were lyophilized and reconstituted them into deionized water. Although reconstitution process caused increase of particle size, drug release behavior of nanoparticles was not significantly changed before and after reconstitution process. The ADR-encapsulated DexLG nanoparticles were less cytotoxic than free ADR plus empty nanoparticles at in vitro, while empty DexLG nanoparticles did not significantly affect cell viability. Even if free ADR plus empty nanoparticles are most effective to inhibit tumor growth at tumor-induced animal model using CT-26 cells, ADR-encapsulated DexLG nanoparticles showed increased survivability of mice. These results indicated that ADR-encapsulated DexLG nanoparticles are promising vehicles for antitumor drug delivery.


Vertebral bone mass, size, and volumetric density in women with spinal fractures.
Bone densitometry provides a measure of bone mass expressed as bone mineral content (BMC) or areal bone mineral density (aBMD). BMC is unadjusted for bone size while aBMD is adjusted for the projected area of the region scanned but not its depth. Because patients with fractures often have reduced bone size, the deficit in BMC or aBMD relative to controls may be partly the result of the comparison of a smaller bone in patients with fractures with a bigger bone in controls without fractures. We asked, what proportion of the deficit in BMC and aBMD found in women with spine fractures relative to controls is attributable to smaller vertebral size? We measured BMC (g), volume (cm3, derived from projected area3/2), aBMD (g/cm2), and volumetric BMD (vBMD, g/cm3) of the third lumbar vertebra by dual-energy X-ray absorptiometry in 270 premenopausal women aged 18-43 years, 163 postmenopausal women with spine fractures aged 54-83 years, and 209 women without fractures aged 54-87 years. The regression of BMC and aBMD on volume in the premenopausal women was used to calculate volume adjusted BMC and aBMD in postmenopausal women with and without fractures (adjusted BMC = observed BMC + [50 - observed volume] x 0.29; adjusted aBMD = observed aBMD + [50 - observed volume] x 0.0044). The data were expressed in the original units and as standard deviation scores (SD) above or below the young normal mean (T scores) or the age predicted mean (Z scores). All results were expressed as mean +/- SEM. Women with spine fractures had reduced BMC (T = -2.35 +/- 0.07 SD, Z = -1.18 +/- 0.06 SD), volume (T = -1.08 +/- 0.08 SD, Z = -0.82 +/- 0.08 SD), aBMD (T = -3. 06 +/- 0.09 SD, Z = -1.14 +/- 0.06 SD) and vBMD (T = -2.67 +/- 0.10 SD, Z = - 0.94 +/- 0.07 SD) (all p < 0.001). About 48% of the difference in BMC between postmenopausal women with and without spine fractures, and about 16% of the difference in aBMD was explained by the difference in vertebral volume between them. When women with and without spine fractures were intentionally matched by aBMD (and age, height, and weight), vertebral volume was reduced (Z = -0.66 +/- 0.13 SD, p < 0.001). When women with and without fractures were intentionally matched by vertebral volume (and age, height, and weight), vBMD was reduced (Z = -1.07 +/- 0.10 SD, p < 0. 001). Women with spine fractures have smaller vertebrae with less bone in the smaller bone. About half the deficit in BMC relative to controls is due to their smaller bone size. The remainder may be due to reduced bone accrual, increased bone loss, or both. Thus, the pathogenesis of bone fragility is heterogeneous. Factors responsible for a deficit in bone mass (due to reduced accrual or excess bone loss) are unlikely to be identified when reduced bone size exaggerates the deficit, and increased bone size obscures it. Understanding the pathogenesis of bone fragility requires acknowledgment of this heterogeneity and the description of its varied morphological basis. This can be achieved by the study of the periosteal and endosteal surfaces of bone because the absolute and relative changes in these surfaces during growth and aging determine skeletal size, its mass, and architecture.


DBU as an N alpha-deprotecting reagent for the fluorenylmethoxycarbonyl group in continuous flow solid-phase peptide synthesis.
The versatility and efficiency of the N alpha-fluorenylmethoxycarbonyl method of solid-phase peptide synthesis have been further enhanced by recent and continuing refinements in side-chain protecting group, linker and amino acid-coupling technology. In contrast, comparatively little work has been carried out on studying and further improving the N alpha-deprotection step. This report demonstrates that, in low concentrations, the non-nucleophilic amidine 1,8-diazabicyclo[5.4.0]undec-7-ene is a preferred alternative to the more commonly employed piperidine for the rapid and efficient cleavage of the N alpha-fluorenylmethoxycarbonyl group in the continuous flow method of solid-phase peptide synthesis. In the cases studied, use of this base did not cause cyclization of Asp(OBut)-Gly or Asn-Gly sequence to succinimide derivatives. At the recommended concentration of 2% 1,8-diazabicyclo[5.4.0]undec-7-ene in dimethylformamide, racemization of resin-bound C-terminal S-trityl cysteine was substantially reduced compared with standard piperidine-mediated deprotection conditions. Additionally, use of the base appears to reduce the extent of broadening of ultraviolet fluorenylmethoxycarbonyl-deprotection peaks occasionally observed when piperidine is employed, indicating that its reaction kinetics and mode of action are different.


Consequences of hypogammaglobulinemia and steroid therapy in severe bronchopulmonary dysplasia.
We retrospectively studied the relation between corticasteroid therapy, hypogammaglobulinemia (HG), and recurrent infections in 37 infants with moderate to severe bronchopulmonary dysplasia (BPD). Nineteen of the 37 patients had tracheostomies because of chronic respiratory failure. We hypothesized that recurrent infections were most prevalent in infants whose IgG levels remained low at one year of age (persistent HG) and in infants receiving high doses of corticosteroids during the first year of life. We further hypothesized that the duration of HG was strongly correlated with the cumulative first year steroid dose. We also studied the response to intravenous gammaglobulin (IVIG) replacement therapy in this population of BPD infants. Our results showed an association between first year corticosteroid dose, duration of HG (r = 0.49, p < 0.003), and frequency of infections (r = 0.51, p < 0.001). We noted a relatively strong correlation between frequency of infections and duration of HG (r = 0.84, p < 0.0001). Twenty-four of 37 (65%) infants showed persistent HG and 49% had evidence of abnormal specific antibody production. Sixty-four percent of infants studied had reduced lymphocyte responsiveness to mitogen stimulation. Nineteen of 37 (51%) infants required IVIG for an average duration of 17.9 months due to recurrent infections. The average number of infections per year decreased from 10.6 to 2.8 (t = 12.32, p < 0.0001). There were no complications associated with IVIG therapy, but one infant died of bronchiolitis obliterans following heart-lung transplantation. Eight of 37 (22%) infants have persistent immunologic dysfunction requiring ongoing IVIG at four years or more of follow-up. We conclude that a substantial number of ill infants with BPD will have immune dysfunction characterized by persistently low IgG levels and reduced specific antibody responsiveness to protein antigens. We speculate that these findings are related to the cumulative dose of corticosteroids received in the first year of life and to the severity of underlying disease.


Malignant childhood neoplasms in the western region of Saudi Arabia.
In a sample of 8 cases of solid malignant neoplasms occurring in children resident in the Western Region of Saudi Arabia the most important finding was a remarkable preponderance of lymphomas when compared with Western series. Other notable differences were the prevalence of Hodgkin's disease in the first decade of life, the different proportions of its subtype, and the occurrence of well-differentiated lymphocytic lymphoma. Included is a case of lympho-epithelioid cellular lymphoma (Lennert's lymphoma) which, as far as we can ascertain, is the youngest reported case. There was a relatively large number of embryonal rhabdomyosarcomas and a paucity of neuroblastomas. Our study, which is concerned with proportional rates (population studies are not yet completed), contributes to the interesting ethnic and geographical differences which exist in the prevalence of childhood lymphomas and other solid malignant neoplasms. The biases that affect studies such as ours are stressed.


Competing endogenous RNA network crosstalk reveals novel molecular markers in colorectal cancer.
The competing endogenous RNA networks play a pivotal role in cancer diagnosis and progression. Novel properstrategies for early detection of colorectal cancer (CRC) are strongly needed. We investigated a novel CRC-specific RNA-based integrated competing endogenous network composed of lethal3 malignant brain tumor like1 (L3MBTL1) gene, long non-coding intergenic RNA- (lncRNA RP11-909B2.1) and homo sapiens microRNA-595 (hsa-miRNA-595) using in silico data analysis. RT-qPCR-based validation of the network was achieved in serum of 70 patients with CRC, 40 patients with benign colorectal neoplasm, and 20 healthy controls. Moreover, in cancer tissues of 20 of the 70 CRC cases were involved in the study. The expression of RNA-based biomarker network in both CRC and adjacent non-tumor tissues and their correlation with the serum levels of this network members was investigated. Lastly, the expression levels of the chosen ceRNA was verified in CRC cell line. Our results revealed that the three RNAs-based biomarker network (long non-coding intergenic RNA-[lncRNA RP11-909B2.1], Homo sapiens microRNA-595 [hsa-miRNA-595], and L3MBTL1 mRNA), had high sensitivity and specificity for discriminating CRC from healthy controls and also from benign colorectal neoplasm. The data suggest that among these three RNAs, serum lncRNA RP11-909B2.1 could be a promising independent prognostic factors in CRC. The circulatory RNA based biomarker panel can act as potential biomarker for CRC diagnosis and prognosis.


Effects of disodium fumarate on in vitro rumen microbial growth, methane production and fermentation of diets differing in their forage:concentrate ratio.
The effects of disodium fumarate on microbial growth, CH4 production and fermentation of three diets differing in their forage content (800, 500 and 200 g/kg DM) by rumen micro-organisms in vitro were studied using batch cultures. Rumen contents were collected from four Merino sheep. Disodium fumarate was added to the incubation bottles to achieve final concentrations of 0, 4 and 8 mm-fumarate, and (15)N was used as a microbial marker. Gas production was measured at regular intervals from 0 to 120 h of incubation. Fumarate did not affect (P>0.05) any of the measured gas production parameters. In 17 h incubations, the final pH and the production of acetate and propionate were increased linearly (P<0.001) by the addition of fumarate. Fumarate tended to increase (P=0.076) the organic matter disappearance of the diets and to decrease (P=0.079) the amount of NH3-N in the cultures. Adding fumarate to batch cultures tended (P=0.099) to decrease CH4 production, the mean values of the decrease being 5.4 %, 2.9 % and 3.8 % for the high-, medium- and low-forage diet, respectively. Fumarate tended to increase (P=0.082) rumen microbial growth for the high-forage diet, but no differences (P>0.05) were observed for the other two diets. These results indicate that the effects of fumarate on rumen fermentation depend on the nature of the incubated substrate, the high-forage diet showing the greatest response.


Attenuation of leptin and insulin signaling by SOCS proteins.
Leptin and insulin are key hormones involved in the regulation of energy balance and glucose homeostasis. Development of resistance to the action of these hormones, which can occur with age, obesity and inflammation, appears to have a prime role in the pathogenesis of obesity and type 2 diabetes. Specific members of the suppressor of cytokine signaling (SOCS) family of proteins are now thought to have a role in the development of leptin and insulin resistance owing to their ability to inhibit leptin and insulin signaling pathways. In the case of leptin, current evidence suggests that SOCS3 appears to be of particular importance in the development of leptin resistance, whereas the ability to diminish insulin action has been described for several SOCS proteins (SOCS1, SOCS3, SOCS6 and SOCS7).


Early anomaly detection in smart home: A causal association rule-based approach.
As the world's population grows older, an increasing number of people are facing health issues. For the elderly, living alone can be difficult and dangerous. Consequently, smart homes are becoming increasingly popular. A sensor-rich environment can be exploited for healthcare applications, in particular, anomaly detection (AD). The literature review for this paper showed that few works consider environmental factors to detect anomalies. Instead, the focus is on user activity and checking whether it is abnormal, i.e., does not conform to expected behavior. Furthermore, reducing the number of anomalies using early detection is a major issue in many applications. In this context, anomaly-cause discovery may be helpful in recommending actions that may prevent risk. In this paper, we present a novel approach for detecting the risk of anomalies occurring in the environment regarding user activities. The method relies on anomaly-cause extraction from a given dataset using causal association rules mining. These anomaly causes are utilized afterward for real-time analysis to detect the risk of anomalies using the Markov logic network machine learning method. The detected risk allows the method to recommend suitable actions to perform in order to avoid the occurrence of an actual anomaly. The proposed approach is implemented, tested, and evaluated for each contribution using real data obtained from an intelligent environment platform and real data from a clinical datasets. Experimental results prove our approach to be efficient in terms of recognition rate.


Two-dimensional nuclear magnetic resonance: exploiting spin echoes to maximize information content by suppression of diagonal peaks in homonuclear experiments.
Two-dimensional nuclear magnetic resonance (2D NMR) correlation spectra help visualize inter- or intra-molecular spin connectivity through space or through bonds. This is accomplished by magnetization transfer between interacting ("connected") spins located at different sites in molecules. In homonuclear 2D experiments, cross peaks which demonstrate spin connectivity and result from magnetization transfer between sites are unfortunately invariably accompanied by other peaks that result from magnetization that has not undergone any transfer, viz., diagonal peaks. The latter can often mask close-lying cross peaks. We report here the general principles that constitute a design strategy for diagonal suppression, relying on echo formation. Next, a novel experiment that effects diagonal suppression in the high-resolution mode is demonstrated. Pure phase capability is also introduced. Examples from both 2D exchange and high-resolution 2D correlation spectroscopy are included, and the proposed method is compared with other established as well as recent attempts to accomplish diagonal suppression.


Bisphenol A induces cholesterol biosynthesis in HepG2 cells via SREBP-2/HMGCR signaling pathway.
Bisphenol A (BPA), an environmental chemical to which humans are commonly exposed, has been shown to increase cholesterol level but the molecular mechanism is not clear. Since cholesterol biosynthesis plays an important role in elevating cholesterol level, the aim of the present study is to explore the effects of BPA on cholesterol biosynthesis in HepG2 cells and its possible mechanisms. HepG2 cells were treated with different concentrations of BPA for 24 hr, the total cholesterol level and the activity of 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) were measured using commercial enzymatic assay kits, and the mRNA and protein expression levels of sterol regulatory element binding protein-2(SREBP-2) and HMGCR were analyzed by qPCR, Western blotting and immunofluorescence, respectively. After treating HepG2 cells with different concentrations (0.1 nM~10 µM) of BPA for 24 hr, we found that BPA at the environmentally relevant concentrations of 1 nM and 10 nM significantly increased the total cholesterol content, the activity and expression of HMGCR in HepG2 cells, but at 100 nM, 1 µM and 10 µM doses, BPA had no stimulatory effect on cholesterol biosynthesis. The whole dose-response relationship follows non-monotonic dose responses, such as an inverted U-shape. Using human SREBP-2 small interfering RNA, we further discovered that the stimulatory effects of BPA on cholesterol biosynthesis and HMGCR expression could be prevented by blockade of the SREBP-2 pathway. This study provides important implications for understanding the potential lipotoxicity of BPA exposure, and it also indicates that low-dose BPA induces hepatic cholesterol biosynthesis through upregulating the SREBP-2/HMGCR signaling pathway.


Evaluation of microparticles containing doxorubicin suitable for aerosol delivery to the lungs.
The efficacy of microparticulate systems containing anticancer agents may be assessed in vitro prior to evaluation of the effects of targeted and controlled drug release on tumor growth. Particles prepared in a size range suitable for aerosol delivery to the lungs (1-5 microm) would be useful in the treatment of locally occurring tumors. Bovine serum albumin microparticles containing doxorubicin (2.6-microm median diameter) were prepared by an emulsion technique with thermal stabilization. Dialysis was used to assess drug release in citrate phosphate buffer pH 4.0 and phosphate buffer pH 7.4, at 37 degrees C. Sixty percent of the doxorubicin load was released in a 10-h burst at pH 4.0. An additional 20% was released up to 70 h. Fifty percent of the drug was released in 70 h at pH 7.4. S180 murine sarcoma cells were incubated with doxorubicin in solution and in microparticle suspension for 24, 48, and 72 h to evaluate cytotoxicity. Viable cells were recovered in smaller numbers following treatment with doxorubicin microparticles than following treatment with doxorubicin solution. The action of doxorubicin on growth of S180 murine sarcoma cells was enhanced in vitro by delivery in microparticles. A four-fold reduction in the effective dose, at which the rate of cell death exceeds replication, was observed for microparticles (5 microg/ml) than for doxorubicin alone (20 microg/ml). Therefore, the doxorubicin microparticles exhibit potential for greater therapeutic effect than drug alone when evaluated in vitro. Further studies are required to demonstrate the aerodynamic properties of these particles and efficacy in an in vivo tumor model.


Pilot study of transurethral needle ablation (TUNA) in treatment of nonbacterial prostatitis.
Transurethral needle ablation (TUNA) was performed on seven patients with chronic nonbacterial prostatitis who failed to respond to conventional treatments administered for more than half a year. The TUNA procedure heated the prostate to a temperature ranging from 90 degrees to 100 degrees C while the urethral temperature was maintained below 43 degrees C by a protective sheath and irrigation. After treatment, four patients showed complete resolution of symptoms and three a partial improvement. All patients had a decrease in the leukocyte count in expressed prostatic secretions (EPS) 1 month after treatment. Recurrence of abnormal inflammatory cells in the EPS was noted in two patients at 3 months after treatment. The subjective improvement has been maintained during the subsequent follow-up. From these results, TUNA is considered to be an effective, safe, and easy treatment for most patients with nonbacterial prostatitis.


Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia.
Genome-wide association studies have identified common variants that only partially explain the genetic risk for type 2 diabetes (T2D). Using genome-wide association data from 1,376 French individuals, we identified 16,360 SNPs nominally associated with T2D and studied these SNPs in an independent sample of 4,977 French individuals. We then selected the 28 best hits for replication in 7,698 Danish subjects and identified 4 SNPs showing strong association with T2D, one of which (rs2943641, P = 9.3 x 10(-12), OR = 1.19) was located adjacent to the insulin receptor substrate 1 gene (IRS1). Unlike previously reported T2D risk loci, which predominantly associate with impaired beta cell function, the C allele of rs2943641 was associated with insulin resistance and hyperinsulinemia in 14,358 French, Danish and Finnish participants from population-based cohorts; this allele was also associated with reduced basal levels of IRS1 protein and decreased insulin induction of IRS1-associated phosphatidylinositol-3-OH kinase activity in human skeletal muscle biopsies.


Snapshots of lignin oxidation and depolymerization in archaeological wood: an EGA-MS study.
Evolved gas analysis-mass spectrometry (EGA-MS) was used for the first time to study archaeological wood, in order to investigate its chemical degradation. The archaeological wood was from an oak pile from a stilt house found in the Neolithic 'La Marmotta' village (Lake Bracciano, Rome, Italy). The sampling was performed from the external to the internal part of the pile, following the annual growth rings in groups of five. In addition, sound oak wood and isolated wood components (holocellulose and cellulose) were also analyzed, and the results were used to highlight differences because of degradation. Our study demonstrated that EGA-MS provides information on the thermo-chemistry of archaeological wood along with in-depth compositional data thanks to the use of MS. Our investigations not only highlighted wood degradation in terms of differences between carbohydrates and lignin content, but also showed that lignin oxidation and depolymerization took place in the archaeological wood. Mass spectral data revealed differences among the archaeological samples from the internal to the external part of the pile. An increase in the formation of wood pyrolysis products bearing a carbonyl group at the benzylic position and a decrease in the amount of lignin dimers were observed. These were related to oxidation and depolymerization reactions, respectively.


Development and performance of a suprathermal electron spectrometer to study auroral precipitations.
The design, development, and performance of Medium-energy Electron SPectrometer (MESP), dedicated to the in situ observation of suprathermal electrons in the auroral ionosphere, are summarized in this paper. MESP employs a permanent magnet filter with a light tight structure to select electrons with proper energies guided to the detectors. A combination of two avalanche photodiodes and a large area solid-state detector (SSD) provided 46 total energy bins (1 keV resolution for 3-20 keV range for APDs, and 7 keV resolution for >20 keV range for SSDs). Multi-channel ultra-low power application-specific integrated circuits are also verified for the flight operation to read-out and analyze the detector signals. MESP was launched from Poker Flat Research Range on 3 March 2014 as a part of ground-to-rocket electrodynamics-electrons correlative experiment (GREECE) mission. MESP successfully measured the precipitating electrons from 3 to 120 keV in 120-ms time resolution and characterized the features of suprathermal distributions associated with auroral arcs throughout the flight. The measured electrons were showing the inverted-V type spectra, consistent with the past measurements. In addition, investigations of the suprathermal electron population indicated the existence of the energetic non-thermal distribution corresponding to the brightest aurora.


A modified Gaines procedure for spondyloptosis.
We present an illustrative case using a modification of the Gaines procedure for the surgical management of patients with spondyloptosis. It involves excision of the inferior half of the body of L5 anteriorly combined with posterior reduction and fusion.


Effect of Arbuscular Mycorrhiza (Glomus etunicatum) on some physiological growth parameters of tomato plant under copper toxicity in solution.
In this study, the effect of the Arbuscular Mycorrhizal fungus Glomus etunicatum on the physiological growth parameters of tomato (Lycopersycium esculentum Mill) plants on the toxicity level of copper was investigated. To explain the physiological growth of these plants, some physiological growth parameters were determined in the shoots and leaves of Arbuscular Mycorrhizal (AM) and non-mycorrhizal (non-AM) plants such as Dry Matter (DM) contents, chlorophyll (chl) content and amount of total sugar. All parameters increased in AM tomato plants compared with those of the non-AM plants. Furthermore, it was determined that P concentration was positively correlated with all chlorophyll and sugar contents. It is concluded that increased P concentration because of the mycorrhizal symbioses, positively affects the physiological performance of tomato plants.


Stimulation of esterified cholesterol accumulation in tissue culture cells exposed to high density lipoproteins enriched in free cholesterol.
Human high density lipoprotein enriched in free cholesterol was obtained by exposing the lipoprotein to lipid dispersions having a free cholesterol/lecithin molar ratio greater than two. The metabolism of cholesterol was studied in tissue culture cells exposed to normal and cholesterol-enriched lipoproteins. Incubation of Fu5-AH rat hepatoma cells in medium containing cholesterol-enriched lipoprotein resulted in the accumulation of cellular cholesterol whereas normal high density lipoprotein produced no change in cellular content. The accumulated sterol was recovered primarily as esterified cholesterol and was derived almost entirely from lipoprotein free cholesterol. The esterification of incorporated free cholesterol and the cellular cholesterol content were directly related to the molar ratio of free cholesterol to phospholipid in the lipoprotein and to the concentration of lipoprotein in the culture medium. Isotopic experiments utilizing lipoprotein labeled with 125I or [4-14C]cholesteryl oleate demonstrated that a large fraction of the cholesterol incorporated from lipoprotein enriched in free cholesterol occurred by mechanisms that did not result in lipoprotein internalization and degradation. The response of other tissue culture cells to cholesterol/phospholipid dispersions is presented. The data indicate that the lipid composition of a lipoprotein can regulate free cholesterol uptake and esterification as well as cellular cholesterol content.


[Secondary bladder amyloidosis with severe recurrent hematuria: transurethral Mickuliz procedure as hemostatic option].
Primary localized amyloidosis of the urinary bladder generally has a benign course. On the contrary, secondary amyloidosis, a consequence of systemic amyloidosis, may have massive bleeding and produce complications such as bladder rupture or life-threatening hemodynamic problems requiring desperate hemostatic procedures such as hypogastric artery embolization or ligature, or cystectomy. We report one case in which hemostasis was achieved by a Mickulicz transurethral bladder tamponage. 58 year old female with very aggressive rheumatoid arthritis and secondary renal amyloidosis under chronic hemodialysis presenting with severe hematuria after hip replacement. An inflamed bladder was found, the biopsy of which showed edema in all layers with blood vessel walls enlarged by amiloyd deposits. After several unsuccessful transurethral hemostatic procedures, intravesical formalin irrigation was carried out together with a Mikulicz type gauze packaging after urethral dilation. The gauze was withdrawn three days later without bleeding recurrence; however she presented subsequent neurological impairment and finally died 14 days after the last urological procedure. Transurethral packaging of the urinary bladder in a woman with massive hematuria is a hemostatic option that we recommend to be used before other more dramatic or invasive options are chosen.


Multiple cantilevers: an alternative to dental implants.
A solution to the problem of missing posterior teeth is presented. The prerequisite for solving this problem is that the remaining teeth must be positioned in one form or another in a triangle, as one can see in Figs. 2, 3 and 4. The tripod effect, in connection with the controlling effect of the mechano-receptors in the periodontal ligaments of the remaining abutment teeth, permit us to construct a functional fixed prosthesis. The feather-edged or knife-edged preparation technique creates long axial walls. Together with the parallel prepared abutment teeth, this must be viewed as the main-retentive feature for fixed prostheses with multiple cantilevers. In extreme situations, where one is uncertain about the outcome of a case, provisional laboratory fabricated restorations are excellent for evaluating the stability of the cross-arch splinted teeth. The whole bridge occasionally shows some mobility. As long as the mobility shows no increase over a period of time, and does not interfere with the patient's chewing ability, a permanent bridge with multiple cantilevers can be inserted. I usually include no more than three cantilevered pontics on each side of the arch in a multiple cantilevered bridge. A second molar is not replaced by a third cantilevered pontic. Its position in the arch may cause an overly strong lever action on the fixed prosthesis.


Ornithine transcarbamylase and arginase I deficiency are responsible for diminished urea cycle function in the human hepatoblastoma cell line HepG2.
A possible cell source for a bio-artificial liver is the human hepatblastoma-derived cell line HepG2 as it confers many hepatocyte functions, however, the urea cycle is not maintained resulting in the lack of ammonia detoxification via this cycle. We investigated urea cycle activity in HepG2 cells at both a molecular and biochemical level to determine the causes for the lack of urea cycle expression, and subsequently addressed reinstatement of the cycle by gene transfer. Metabolic labelling studies showed that urea production from 15N-ammonium chloride was not detectable in HepG2 conditioned medium, nor could 14C-labelled urea cycle intermediates be detected. Gene expression data from HepG2 cells revealed that although expression of three urea cycle genes Carbamoyl Phosphate Synthase I, Arginosuccinate Synthetase and Arginosuccinate Lyase was evident, Ornithine Transcarbamylase and Arginase I expression were completely absent. These results were confirmed by Western blot for arginase I, where no protein was detected. Radiolabelled enzyme assays showed that Ornithine Transcarbamylase functional activity was missing but that Carbamoyl Phosphate Synthase I, Arginosuccinate Synthetase and Arginosuccinate Lyase were functionally expressed at levels comparable to cultured primary human hepatocytes. To restore the urea cycle, HepG2 cells were transfected with full length Ornithine Transcarbamylase and Arginase I cDNA constructs under a CMV promoter. Co-transfected HepG2 cells displayed complete urea cycle activity, producing both labelled urea and urea cycle intermediates. This strategy could provide a cell source capable of urea synthesis, and hence ammonia detoxificatory function, which would be useful in a bio-artificial liver.


A rational attitude toward serum alanine aminotransferase measurement by blood banks, based on a longitudinal study of a cohort of repeat blood donors.
A cohort of 879 blood donors was followed over a 3-year period. Of the 3858 units of blood collected, 112 (2.9%), obtained from 64 donors, had an alanine aminotransferase (ALT) activity over 45 IU per L; of these, 39 had a single ALT elevation. The incidence of ALT increase was 2.01 per 100 units, or 5.1 per 100 donors, per year. The pattern of elevated ALT was followed in 72 donors, 54 of whom were from the 64 cited above. At the second blood donation (BD2), about 5 months later, 62.5 percent had a normal ALT value, and most (91%) retained those values at blood donation 3 (BD3). However, 19 (70.3%) of the 27 whose ALT levels had not returned to normal at BD2 had an increased value at BD3. These results led to the formulation of the following algorithm to improve the management of blood donors; at the first donation, the ALT assay is done after the blood collection, but, at the next donation, the ALT level is measured before donation if the preceding ALT activity had been abnormal. If ALT is elevated, blood is not collected. Three consecutive ALT elevations are a criterion for permanent exclusion of the donor.


Effects of pitavastatin (LIVALO Tablet) on high density lipoprotein cholesterol (HDL-C) in hypercholesterolemia.
Low high-density lipoprotein cholesterol (HDL-C) is an important clinical risk factor for cardiovascular disease (CVD). Statins have been known to have a potent HDL-C-elevating effect in addition to low-density lipoprotein cholesterol (LDL-C)-lowering effects. The database of LIVALO effectiveness and safety (LIVES) Study, a large-scale (n=20,279), long-term (104 weeks), prospective post-marketing surveillance of hypercholesterolemic patients treated with pitavastatin, was used to evaluate and analyze effects on plasma lipids, especially focusing on HDL-C. Total cholesterol (TC) (-21.0%) and LDL-C (-31.3%) were significantly reduced. The decrease in triglyceride (TG) was significant in hypertriglyceridemic patients. HDL-C was elevated by 5.9% and 24.6% in all and in patients with low HDL-C levels (less than 40 mg/dL) at baseline, respectively (p<0.0001). In time-course analysis, elevation of HDL-C in the low HDL-C group was enhanced by 14.0% and 24.9% at 12 weeks and 104 weeks, respectively. A significant increase in HDL-C by pitavastatin treatment was also observed after switching from other statins. Multivariable analysis showed that BMI, diabetes, liver disease, and pre-treated other cholesterol-lowering drugs emerged as significant factors influencing HDL-C. Pitavastatin had stable clinical effects on LDL-C, TG, and HDL-C for 104 weeks. It was noteworthy that HDL-C in patients with low HDL-C was continuously increased by this agent during the period tested.


Depression in later life: A closer look at the gender gap.
Gender differences in depressive symptoms have been extensively documented, with women reporting a higher number of depressive symptoms than men. However, studies offer different explanations for why such a gap exists. The goal of the current paper is to analyze how much of the observed gender gap in depression may be attributed to (1) compositional versus (2) reporting differences or (3) differences in reactivity to adversities. We contribute to this literature by testing, net of compositional differences, whether the relationship between reporting behavior and depressive symptoms is gendered and whether accounting for the possibility of gender-specific reactivity alters the structure of the gender gap at older ages. Our results show that the observed gender gap in depression (1) only partially derives from compositional differences; (2) is not an artifact of a gender-specific reporting style; and remarkably (3) men appear more sensitive to adversities.


Prevalence and correlates of prostatitis in the health professionals follow-up study cohort.
Prostatitis is an ill-defined condition whose symptoms overlap with benign prostatic hyperplasia (BPH). Little is known about the prevalence and correlates of prostatitis, or factors that distinguish prostatitis from BPH. We examined these issues in a large, nationwide sample of healthy men. In 1992, 31,681 United States health professionals without prostate cancer provided information on urological diagnoses, lower urinary tract symptoms, and demographic, clinical and lifestyle factors. We calculated age adjusted odds ratios and 95% confidence intervals for these correlates predicting a history of prostatitis. We also compared characteristics of men with prostatitis to those with BPH. The prevalence of a self-reported history of prostatitis was 16%. Men reporting a history of BPH had 7.7-fold greater odds of a history of prostatitis, those with moderate or severe lower urinary tract symptoms had 1.8 and 2.8-fold greater odds, respectively, those with a history of sexually transmitted disease had 1.8-fold greater odds and those reporting stress at home or work had 1.5- and 1.2-fold greater odds, respectively. The 2,163 men with prostatitis alone were younger and had less severe urinary tract symptoms (but a similar pattern of symptoms) than the 4,575 men with BPH alone. Self-reported prostatitis was common among healthy men of all ages but there was considerable overlap with self-reported BPH. Prostatitis had several identifiable correlates that may aid in its recognition.


Stabilization of cytochrome P450j messenger ribonucleic acid in the diabetic rat.
Cytochrome P450j, an enzyme involved in nitrosamine metabolism, is expressed in hepatic, pulmonary, and renal tissues and its level is elevated in ethanol- and acetone-treated rats as well as in diabetic rats induced by either streptozotocin or alloxan. Although P450j protein is substantially elevated by all inducing regimens, only in diabetic rats is P450j mRNA increased 10-fold. Nuclear run-on transcription analysis showed that this mRNA increase is not due to transcriptional activation but is due to specific stabilization of the P450j mRNA.


A reappraisal of Richter's syndrome. Development of two phenotypically distinctive cell lines in a case of chronic lymphocytic leukemia.
Richter's syndrome, the development of a malignant lymphoma in a patient with preexisting chronic lymphocytic leukemia (CLL) is an infrequent but well-documented phenomenon generally thought to represent a monoclonal proliferation of B-lymphocytes arising from the CLL. A heterogeneous population of cells consisting of sheets of transformed lymphocytes in combination with clusters of bizarre, atypical histiocytes developed in a patient with a history of longstanding CLL. Immunocytochemistry using a panel of monoclonal and polyclonal antibodies by immunoperoxidase techniques identified the presence of both B-lymphocytic and monocytic-histiocytic cell lines of differentiation. A mechanism of multiple differentiation is proposed to account for the dual cell population observed in this patient. Review of the literature appears to indicate that this phenomenon often may be involved in cases diagnosed as Richter's syndrome. The demonstration of cellular heterogeneity in the current case underscores the need for establishing a more precise definition for the histologic characterization of the terminal malignancy in Richter's syndrome.


Potent and rapid antigonococcal activity of the venom peptide BmKn2 and its derivatives against different Maldi biotype of multidrug-resistant Neisseria gonorrhoeae.
The emergence of multidrug-resistant strains of Neisseria gonorrhoeae constitutes a serious threat to public health and necessitates the discovery of new types of antimicrobial agents. Among the 18 clinical isolates of N. gonorrhoeae with susceptible to spectinomycin, ceftriaxone and cefixime, 14 isolates were resistance to penicillin, tetracycline and ciprofloxacin, while 2 isolates were susceptible to tetracycline and another was penicillin intermediate isolate. Significant differences between laboratory strain and multidrug resistant strains were revealed by means of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry profiling and bioinformatics examination using the MALDI BioTyper software. However, Maldi Biotyper was not successfully separated ciprofloxacin-penicillin resistance and ciprofloxacin-tetracycline resistance from ciprofloxacin-penicillin-tetracycline resistant N. gonorrhoeae isolates. BmKn2 is a basic, alpha-helical peptide with no disulfide-bridge venom peptides that was first isolated from Buthus martensii Kasch. A panel of BmKn2 scorpion venom peptide and its derivatives of varying length and characteristics were synthesized chemically and evaluated for their ability to inhibit the growth of clinical N. gonorrhoeae isolates. Synthetic BmKn2 displayed potent activity against 18 clinical isolates of N. gonorrhoeae with MIC50 values of 6.9-27.6 μM. BmKn2 exerted its antibacterial activity via a bactericidal mechanism. Cyclic BmKn1 did not show antigonococcal activity. Decreasing the cationicity and helix percentage at the C-terminus of BmKn2 reduced the potency against N. gonorrhoeae. Taken together, the BmKn1 peptide can be developed as a topical therapeutic agent for treating multidrug-resistant strains of N. gonorrhoeae infections.


Business models and leadership styles in small medical device and bio-science businesses--examples in a region and their implications.
This paper reviews the leadership styles and business models found in small technologically based businesses operating in the healthcare sector within one of the UK regions, the East Midlands. The most frequently encountered business model strands were 1) mixed economies: that fund development with service income; cross-sectoral product portfolios; and decoupled business portfolios led by a single entrepreneur and 2) scale sensitive "stay small" models including the avoidance of venture capital; "early exit"; and virtual business strands. There was found to be little correlation between leadership style and business model for the small number of businesses surveyed. The avoidance of venture capital is in direct contrast to adjacent regions.


Power of the Past, Celebrate the Present, Force of the Future, Part 3: Interview With NASN Leaders.
For Part 3 of the NASN School Nurse series exploring NASN's past, present, and future, Lindsey Minchella interviews NASN President, Nina Fekaris and President-elect, Laurie Combe to discuss their school nursing perspective and philosophies. These three school nursing leaders discuss what is responsible for their long tenure as school nurses, changes witnessed in student health over the years, how NASN makes a difference for students and school nurses, the future of school nursing, and the power of NASN members' voices to improve student health and academic outcomes.


Recovery of Acid-Gas-Degraded Zeolitic Imidazolate Frameworks by Solvent-Assisted Crystal Redemption (SACRed).
The acid stability of zeolitic imidazolate frameworks (ZIFs) is an important issue hindering their application. Acid-gas damage of ZIFs has been considered irreversible. However, we demonstrate a methodology called solvent-assisted crystal redemption (SACRed) to reverse acid-gas damage to ZIFs with a high degree of structural and functional recovery. For example, post-SACRed ZIF-8 is shown to be structurally and chemically near-identical with the original pristine ZIF-8 that suffered a large loss of surface area, porosity, and crystallinity during acid-gas exposure. We also provide mechanistic insight into the recovery process using deuterium-labeled linkers and 2H NMR spectroscopy. SACRed treatments could allow large extensions in the lifetime of ZIF-based membranes and adsorbents that degrade over time.


Role of Marine Snows in Microplastic Fate and Bioavailability.
Microplastics contaminate global oceans and are accumulating in sediments at levels thought sufficient to leave a permanent layer in the fossil record. Despite this, the processes that vertically transport buoyant polymers from surface waters to the benthos are poorly understood. Here we demonstrate that laboratory generated marine snows can transport microplastics of different shapes, sizes, and polymers away from the water surface and enhance their bioavailability to benthic organisms. Sinking rates of all tested microplastics increased when incorporated into snows, with large changes observed for the buoyant polymer polyethylene with an increase in sinking rate of 818 m day-1 and for denser polyamide fragments of 916 m day-1. Incorporation into snows increased microplastic bioavailability for mussels, where uptake increased from zero to 340 microplastics individual-1 for free microplastics to up to 1.6 × 105 microplastics individual-1 when incorporated into snows. We therefore propose that marine snow formation and fate has the potential to play a key role in the biogeochemical processing of microplastic pollution.


Stent fabric fatigue of grafts supported by Z-stents versus ringed stents: an in vitro buckling test.
Stent-grafts externally fitted with a Z-shaped stents were compared to devices fitted with ringed stents in an in vitro oscillating fatigue machine at 200 cycles per minute and a pressure of 360 mmHg for scheduled durations of up to 1 week. The devices fitted with Z-stents showed a considerably lower endurance limit to buckling compared to the controls. The contact between the apexes of adjacent Z-stents resulted in significant damage to the textile scaffolds and polyester fibers due to the sharp angle of the Z-stents. The ringed stents did not cause any fraying in the textile scaffolds.


[Clinical observation of different needle retention times for acute lumbar sprain treated with float needle].
To observe the difference of the clinical effects of different needle retention times for acute lumbar sprain treated with float needle. One hundred and twenty patients with acute lumbar sprain were randomly divided into a 6 h group, a 12 h group, a 24 h group and a western medication group, 30 cases in each one. In the three float needle groups, plastic hose was detained near the pressure pain point on the lumbar after subcutaneous scattering with float needle. The needle retention time was 6 h, 12 h and 24 h respectively. In the western medication group, 75 mg voltaren tablet was adopted orally every day and the treatment was given for four days. Visual analogue scale (VAS) and Oswestry dysfunction index (ODI) about low back pain were observed before and after treatment. Also, the comprehensive effect was assessed after treatment. After treatment, the VAS scores and the ODI scores were improved obviously than those before treatment in all groups (all P< 0. 05). In the three float needle groups, the VAS scores and the ODI scores were superior to those in the western medication group (all P<0. 05). The differences in VAS scores and ODI scores among the three float needle groups were not statistically significant after treatment (all P>0. 05). The effective rate in the 6 h, 12 h and 24 h group was 93. 3% (28/30), 90. 0% (27/30) and 93. 3% (28/30) respectively, which were better than 73. 3% (22/30) in the western medication group (all P<0. 05). The effect of float needle for acute lumbar sprain is better than voltaren, and there is no apparent difference in retention times.


Improved survival at 2 and 5 years in the LMCE1 unselected group of 72 children with stage IV neuroblastoma older than 1 year of age at diagnosis: is cure possible in a small subgroup?
The objectives of this study were to determine (1) the role of selection before bone marrow transplantation (BMT), (2) the role of vincristine, melphalan, and total body irradiation (TBI) as consolidation of induction therapy for stage IV over 12 months at diagnosis, and (3) the role of immunomagnetic purging in metastatic neuroblastoma. Among 72 consecutive unselected patients, 10 were not grafted (four died at induction: two in complete remission [CR], two in partial remission [PR]); three had bone marrow progression before harvest; one had uncontrolled progression; and two had parental refusal). Sixty-two patients were grafted (23 in CR/very good PR [VGPR] and 39 in PR). Among the 62, 33 were consolidated with at least 90% excision of their initial tumor excised (53.2%), 15 with catecholamine secretions (24.2%), 22 with minor bone marrow involvement (35.5%), and 31 with positive bone scan (50%). Median observation time is 59 months. Progression-free survival (PFS) for the 10 excluded patients was 20% at 2 years and 0% at 4 years. PFS for the grafted population (n = 62) is 40% at 2 years, 20% at 4 years, and 13% at 7 years. No difference was observed between patients grafted in CR/VGPR or in PR. However, a group of 19 children was grafted resulting in complete normalization of metastasis (regardless of primary-site tumor status). In this group, PFS at 59 months was 38% with no relapses up to 7 years post-BMT. A group of 31 patients with no bone involvement at BMT was also identified. PFS at 5 years is 30% compared with 12% for bone-positive patients at BMT. Moreover, the 11 children presenting at diagnosis with no bone involvement (Evans stage IVS or stage C Memphis) and consolidated with BMT had PFS at 5 years of 50% with no late relapses. A subgroup of stage IV neuroblastoma patients older than 1 year of age at diagnosis may be curable with this therapeutic approach, and the use of multivariate analyses to search for prognostic factors is warranted in currently existing international registries.


Transformation of bacteria with plasmid DNA by electroporation.
The possibility of electric field-mediated transformation ("electroporation") of a gram-positive bacterium (Enterococcus faecalis) and two gram-negative bacteria (Escherichia coli and Pseudomonas putida) with plasmid DNA was investigated. E. faecalis protoplasts could be transformed by electroporation with a transformation frequency of 10(4) to 10(5) transformants/micrograms plasmid. Untreated--i.e., washed--cells of E. coli could be transformed with rates of 1 X 10(5) transformants/micrograms plasmid DNA. Transformation rates for P. putida cells were up to 3 X 10(4) if the method developed for E. coli was used. Detailed protocols for these systems, including the results of various optimization experiments, are given.