Comment on 'Modeling the conductance and DNA blockade of solid-state nanopores'.

Recently, Kowalczyk et al (2011 Nanotechnology 22 315101) introduced a model for calculating the conductance of an hourglass-shaped nanopore, and the conductance change when DNA is introduced into such a pore. Here, we comment on their model in the context of other literature addressing the same general problem. Existing work includes widespread use of an alternative model, contradicts the authors' claim that the conductance change should be expected not to vary with pore size, and has frequently utilised access resistance.

Clinical field study to evaluate the efficacy and safety of the amino-acetonitrile derivative, monepantel, compared with registered anthelmintics against gastrointestinal nematodes of sheep in Australia.

OBJECTIVE: To determine the efficacy of monepantel, a developmental compound from the amino-acetonitrile derivative class of anthelmintics, against field infections of gastrointestinal nematodes in sheep. PROCEDURES: Comparisons of efficacy (using standard faecal worm egg count reduction tests) and safety (on the basis of visual observations) were made in a large-scale field study in Australia, between groups of sheep treated with either an oral solution of monepantel or a registered anthelmintic. The sheep were naturally infected with the major gastrointestinal nematode genera present in Australia. RESULTS: The post-treatment efficacy results for monepantel were: at 7 days (+/-1 day) efficacy was >98%; at 14 days (+/-1 day) it was generally close to or >99%; and at 21 days (+/-1 day) efficacy was consistently >99%. A high proportion of the targeted nematode populations were confirmed as being resistant to one or more of the currently available anthelmintic classes. CONCLUSIONS: Monepantel when used under field conditions at a minimum dose rate of 2.5 mg/kg was highly effective against mixed-genus natural field infections of the major gastrointestinal nematode genera including Haemonchus, Teladorsagia (Ostertagia), Trichostrongylus, Nematodirus, Chabertia and Oesophagostomum. This result included efficacy against some populations resistant to the currently available broad-spectrum anthelmintics. Few Cooperia spp. were present to allow confirmation of efficacy against this genus. On no occasion after treatment did any commercial anthelmintic-treated groups have significantly lower faecal egg counts than the monepantel-treated groups. Monepantel was safe for the target animals and human operators when used in a field situation.

A large-scale clinical field study to evaluate the efficacy and safety of an oral formulation of the amino-acetonitrile derivative ( AAD ), monepantel , in sheep in New Zealand.

AIM: To evaluate the efficacy and safety of an oral formulation of the novel anthelmintic, monepantel (AAD 1566), in sheep, in comparison with some other anthelmintics currently registered in New Zealand. METHODS: A study was conducted on 18 farms located throughout the North and South Islands of New Zealand. On each farm, sheep naturally infected with the target nematodes were randomly assigned to groups, which were then treated with either monepantel, at a minimum dose rate of 2.5 mg/kg, or one of five other anthelmintics encompassing the range of single-entity and combination formulations that are commercially available in New Zealand, or left untreated as controls. Faecal samples were collected from all sheep pre-treatment (1-3 weeks before treatment), at the time of treatment, and approximately 1, 2 and 3 weeks after treatment (Days 7, 14 and 21). Faecal nematode egg counts (FEC) were measured in all samples, and the efficacy of treatments, as indicated by reductions in FEC, calculated. All sheep were inspected at least daily, to check for any adverse effects of treatment. RESULTS: On all 18 farms, on Days 7, 14 and 21 (54 test points), the efficacy of the monepantel solution was >95%. At Days 7 and 14 post-treatment, efficacies>99% were recorded in 15 flocks. At Day 21 post-treatment, efficacies>98% were recorded in 13 flocks. Monepantel was as effective, or more effective, than the registered anthelmintics with which it was compared. Moreover, it was effective against strains of nematodes resistant to one or more of the currently available broad-spectrum anthelmintics. The monepantel solution used in this study was well tolerated by the sheep, and no adverse events could be attributed to its use. CONCLUSIONS AND CLINICAL RELEVANCE: When administered as an oral formulation under field conditions, at a minimum dose rate of 2.5 mg/kg, monepantel appeared to be highly effective against all the major genera of gastrointestinal nematodes of sheep, including Haemonchus, Teladorsagia (=Ostertagia), Trichostrongylus, Cooperia, Nematodirus, Chabertia and Oesophagostomum. This included strains resistant to the currently available broad-spectrum anthelmintics. Monepantel is the first compound from the recently discovered amino-acetonitrile derivative (AAD) class of anthelmintics to be developed for use in sheep.

Variant Klinefelter syndrome 47,X,i(X)(q10),Y and normal 46,XY karyotype in monozygotic adult twins.

Klinefelter syndrome (KS; 47, XXY) is characterized by increased body height, hypergonadotrophic hypogonadism, and infertility. We describe a patient with a variant KS (47,X,i(Xq),Y) who has a twin brother with a 46,XY karyotype. Molecular studies showed that the twins were monozygotic. The presence of an isochromosome Xq in one of two monozygotic twins allows precise investigation of its phenotypic effect. The patient was somewhat shorter (3.5 cm) and had a smaller volume of the testes (8 vs. 18 ml) as compared to his twin brother. Furthermore he had increased gonadotrophin levels and an extreme oligoasthenoteratozoospermia (OAT). These data support the view that genes on Xp cause increased body height and genes on Xq cause infertility in KS. To our knowledge this is the first report on a heterokaryotypic monozygotic twin with a variant KS.

A globally applicable location-specific screening model for assessing the relative risk of pesticide leaching.

A screening model of pesticide leaching loss is described which forms part of a multi-criteria risk-based indicator system called PRoMPT (Pesticide Risk Management and Profiling Tool). The leaching model evaluates pesticide fate in soil for any application rate and time of application (including multiple applications), for any land-based location in the world. It considers a generic evaluative environment with fixed dimensions and soil properties. The soil profile is conceptualised as a number of discrete layers. Equilibrium partitioning between adsorbed and dissolved chemical (based on the organic carbon-water partition coefficient [K(OC)]) is assumed in each time step, in each layer. Non-leaching losses are described using first order kinetics. Drainage is assumed to be uniform throughout the soil profile but varies temporally. The drainage rate, which can be augmented by evapotranspiration-adjusted irrigation, is derived from long-term mean monthly water balance model calculations performed for 30 arc-minute grid cells across the entire ice-free land surface of the earth. Although, such predictions are approximate, they do capture the seasonality and relative magnitude of drainage and allow the model to be applied anywhere, without the need for extensive data compilation. PRoMPT predictions are shown to be consistent with those made by more sophisticated models (PRZM, PELMO and PEARL) for the FOCUS groundwater scenarios.

Natural atypical Listeria innocua strains with Listeria monocytogenes pathogenicity island 1 genes.

Identification of bona fide Listeria isolates into the six species of the genus normally requires only a few tests. Aberrant isolates do occur, but even then only one or two extra confirmatory tests are generally needed for identification to species level. We have discovered a hemolytic-positive, rhamnose and xylose fermentation-negative Listeria strain with surprising recalcitrance to identification to the species level due to contradictory results in standard confirmatory tests. The issue had to be resolved by using total DNA-DNA hybridization testing and then confirmed by further specific PCR-based tests including a Listeria microarray assay. The results show that this isolate is indeed a novel one. Its discovery provides the first fully documented instance of a hemolytic Listeria innocua strain. This species, by definition, is typically nonhemolytic. The L. innocua isolate contains all the members of the PrfA-regulated virulence gene cluster (Listeria pathogenicity island 1) of L. monocytogenes. It is avirulent in the mouse pathogenicity test. Avirulence is likely at least partly due to the absence of the L. monocytogenes-specific allele of iap, as well as the absence of inlA, inlB, inlC, and daaA. At least two of the virulence cluster genes, hly and plcA, which encode the L. monocytogenes hemolysin (listeriolysin O) and inositol-specific phospholipase C, respectively, are phenotypically expressed in this L. innocua strain. The detection by PCR assays of specific L. innocua genes (lin0198, lin0372, lin0419, lin0558, lin1068, lin1073, lin1074, lin2454, and lin2693) and noncoding intergenic regions (lin0454-lin0455 and nadA-lin2134) in the strain is consistent with its L. innocua DNA-DNA hybridization identity. Additional distinctly different hemolytic L. innocua strains were also studied.

Developing an index of restorative dental treatment need.

The process undertaken to establish an initial pilot index for restorative dental treatment is described. Following consultation with a wide range of clinicians and others, an outline framework for the index was developed and comprised three main components: 1. Patient identified need for treatment: the data from the patient perceived need questionnaire were inconclusive; 2. Complexity of treatment (assessed by clinicians): this was found to be a practical tool capable of being used by a range of dentists. A booklet has been produced which describes the process of using the scoring system; 3. Priority for treatment (assessed by clinicians): three levels of priority were identified; the highest priority was assigned to patients with inherited or developmental defects that justify complex care (eg clefts of the lip and palate). The initial development of the index has had some success in a difficult area. The treatment complexity component is the most developed and may allow both referrers and commissioners of specialist restorative dentistry to determine appropriate use of skilled clinicians' expertise.

Ferulic acid is esterified to glucuronoarabinoxylans in pineapple cell walls.

The ester-linkage of ferulic acid (mainly E) to polysaccharides in primary cell walls of pineapple fruit (Ananas comosus) (Bromeliaceae) was investigated by treating a cell-wall preparation with 'Driselase' which contains a mixture of endo- and exo-glycanases, but no hydroxycinnamoyl esterase activity. The most abundant feruloyl oligosaccharide released was O-[5-O-(E-feruloyl)-alpha-L-arabinofuranosyl](1-->3)-O-beta-D-xylopyranosyl-(1-->4)-D-xylopyranose (FAXX). This indicated that the ferulic acid is ester-linked to glucuronoarabinoxylans in the same way as in the primary walls of grasses and cereals (Poaceae). Glucuronoarabinoxylans are the major non-cellulosic polysaccharides in the pineapple cell walls.

Effectiveness of the boston brace in treatment of large curves in adolescent idiopathic scoliosis.

STUDY DESIGN: This is a retrospective study of 50 patients with adolescent idiopathic scoliosis with curves measuring 35 degrees to 45 degrees who were treated with a Boston brace. OBJECTIVES: The purpose of this study was to determine whether the Boston brace could effectively halt long-term progression in skeletally immature adolescents with idiopathic scoliosis who had a curve between 35 degrees and 45 degrees. SUMMARY OF BACKGROUND DATA: The Boston brace has been shown to be effective in preventing curve progression in adolescent idiopathic scoliosis, but its efficacy in large curves has not been fully studied. METHODS: Fifty adolescents were treated with a Boston brace for idiopathic scoliosis curves of 35-45 degrees (mean, 38.55 degrees ). All were judged to be skeletally immature based on menarcheal status (mean, 2.6 months before menarche), Risser sign (mean, 0.90; range, 0-2), and chronologic age (mean, 13 +/- 1 years). Patients were recalled for long-term follow-up at a mean of 9.7 years (range, 6.23-13.22 years) after brace discontinuation. Three well-matched patient subsets were then identified based on compliance. Group 1 (n = 24) consisted of patients who were compliant with the brace program and wore the brace 18 or more hours per day, Group 2 (n = 14) contained patients who wore the brace 12-18 hours per day, and Group 3 (n = 12) contained patients who wore the brace 0-12 hours per day. RESULTS: There was a significant difference in the amount of initial correction seen in the brace between the groups: 49%, 45%, and 33% curve correction in the brace for Groups 1, 2, and 3, respectively (P < 0.05). At long-term follow-up there was a statistically significant difference between Groups 1, 2, and 3 in the percentage of patients in whom the curve had progressed to more than 45 degrees (P < 0.001), who had more than 5 degrees of curve progression (P < 0. 05), or who had undergone posterior spinal fusion (P < 0.001). CONCLUSIONS: These long-term data confirm that the Boston brace when used 18 or more hours per day is effective in preventing progression of large curves at a mean of 9.8 years after bracing is discontinued.

Oral pH and drinking habit during ingestion of a carbonated drink in a group of adolescents with dental erosion.

OBJECTIVES: To investigate the relationship between dental erosion, oral pH and drinking habit in a group of adolescents. METHODS: Oral pH was measured simultaneously at the surface of four teeth in 11 patients, aged 10-16 years, with erosion and in 10 controls subjects without erosion using antimony electrodes. Measurements were made before, during and after drinking 330 ml of a carbonated drink. The method and timing of drinking the beverage, reported dietary intake of acidic foods and flow rate and buffering capacity of saliva were recorded. RESULTS: The erosion patients reported drinking more carbonated drinks (p<0.01) and drinking directly from a can more frequently than the controls (p<0.05). They also drank twice as quickly (p<0.05). The pH at the buccal surface of a molar remained lower for longer in the erosion patients than in the patients without erosion (p<0.01), whilst the labial surface of the upper central incisor had a longer exposure to low pH in the controls subjects (p<0.05). CONCLUSION: The pattern of oral pH differed between subjects with and without erosion after drinking an acidic beverage. This may be related to observed differences in drinking habit, which could have influenced the pattern of erosion in these subjects.

Dielectric resonator-based side-access probe for muscle fiber EPR study.

We present a novel dielectric resonator (DR)-based resonant structure that accommodates aqueous sample capillaries in orientations that are either parallel (i.e., side-access) or perpendicular to the direction of an external (Zeeman) magnetic field, B(0). The resonant structure consists of two commercially available X-band DRs that are separated by a Rexolite spacer and resonate in the fundamental TE(01delta) mode. The separator between the DRs is used to tune the resonator to the desired frequency and, by appropriately drilled sample holes, to provide access for longitudinal samples, notably capillaries containing oriented, spin-labeled muscle fibers. In contrast to the topologically similar cylindrical TE(011) cavity, the DR-based structure has distinct microwave properties that favor its use for parallel orientation of lossy aqueous samples. For perpendicular orientation of a dilute (6.25 microM) aqueous solution of IASL spin label, the S/N ratio was at least one order of magnitude better for the side-access DR-based structure than for a standard TE(102) cavity. EPR spectra acquired for maleimide spin-labeled myosin filaments also revealed ca. 10 times better S/N ratio than those obtained with a standard TE(102) cavity. For the side-access DR with sample capillaries oriented either parallel or perpendicular to the external magnetic field, the Q- and filling factors are in good agreement with the theoretical estimates derived from the distribution of magnetic (H(1)) and electric (E(1)) components.

The role of the esophagus in dental erosion.

OBJECTIVE: The aim of this study was to measure lower esophageal sphincter pressure, sphincter length, and esophageal motility in patients with dental erosion and compare the results with measurements made in patients without gastroesophageal reflux or dental erosion. STUDY DESIGN: Lower esophageal sphincter length and esophageal motility were measured in 39 patients (age range, 15-74 years) with dental erosion through use of static esophageal pressure monitoring; the data were compared with those from 10 control subjects (age range, 26-46 years) with nonparametric statistical tests. RESULTS: Median lower esophageal sphincter pressure was 9 mmHg (range, 0-26 mmHg) in the patients with erosion and 9.5 mmHg (range, 0 -14 mmHg) in the controls; there was no statistically significant difference between the two subject groups. Similarly, there was no statistically significant difference in esophageal length between the subject groups. There was a statistically significant difference between the groups (P =.01) in the measurement of esophageal motility; the median value was 8% (range, 0% to 100%) in the patients with erosion and 0% (range, 0% to 18%) in the controls. CONCLUSIONS: It appears that esophageal motility in patients with dental erosion is more likely to be associated with low amplitude changes than with sphincter pressure alone. Poor esophageal motility may therefore be a risk factor in regurgitation erosion.

A literature review of the techniques to measure tooth wear and erosion.

This paper reviews methods to measure tooth wear especially those more recently introduced as a result of improvements in technology. The review searched methods to measure tooth wear and dental erosion from large epidemiological investigations, in vitro and in vivo studies. There seems to be wide variation in techniques used to measure tooth wear and erosion. In vitro techniques may have little direct clinical relevance but can lead to new and more accurate clinical methods. In vivo studies have problems with reference points and accurate validation of the techniques. There is a need for a simple, reliable technique to quantify tooth wear due to erosion.

The role of saliva in regurgitation erosion.

It has been suggested that salivary characteristics are important in the progression of erosion. The aim of this investigation was to measure salivary parameters in 22 patients with erosion, 10 with normal (non-pathological) levels of reflux (Group I) and 12 with previously diagnosed pathological levels of gastro-oesophageal reflux (Group II). A further 10 subjects without evidence of erosion and no history of reflux disease acted as controls (Group III). No statistically significant differences in salivary flow rate, buffering power or the concentrations of calcium, phosphorus and fluoride were detected. The results suggest that variation in the characteristics of unstimulated and stimulated saliva collected during waking hours do not have a major role in erosion.

Results and morbidity in a consecutive series of patients undergoing spinal fusion for neuromuscular scoliosis.

STUDY DESIGN: A retrospective clinical and radiographic review. OBJECTIVES: To provide current data on the results and complications of patients who have undergone spinal fusion for neuromuscular scoliosis at a center with physicians experienced in these types of cases. SUMMARY OF BACKGROUND DATA: The reported complication rate in the management of neuromuscular scoliosis ranges from 44% to 62% in the recent literature. This literature is that of 1991 or earlier reflecting operative techniques of the mid-1980s, and it has been used to argue against the efficacy of neuromuscular spinal fusions. METHODS: A retrospective chart and radiographic review of 50 consecutive spinal fusions for neuromuscular scoliosis was performed at Connecticut Children's Medical Center between January 1990 and January 1994. The three most common diagnoses were spastic quadriplegic cerebral palsy (20 patients), myelomeningocele (13 patients), and muscle disease (8 patients). There were 38 posterior spinal fusions including two kyphectomies and 12 anteroposterior spinal fusions. The Luque-Galveston technique was used in 39 of 50 patients. The average age at surgery was 13 years and 6 months, with an average follow-up of 40 months (minimum, 24 months). RESULTS: Before surgery, the mean major scoliosis measured 72 degrees, with mean best bend or traction view of 35 degrees. At most recent follow-up, the mean scoliosis magnitude was 25 degrees (mean correction, 65%). There were 17 minor complications in 14 patients and three major complications (deep wound infections) in three myelomeningocele patients. Rod breakage was noted in two patients, one of whom had an asymptomatic pseudarthrosis. There were no neurologic complications or deaths, and none of the complications affected the final results. CONCLUSIONS: The data in the current study support the authors' belief that with current surgical techniques and perioperative management in an experienced center, the results for patients undergoing spinal fusion for neuromuscular scoliosis have been improved, and major complications have been minimized.

Dose proportionality and pharmacokinetics of oral transmucosal fentanyl citrate.

BACKGROUND: The pharmacokinetics of a single dose (15 microg/kg) of oral transmucosal fentanyl citrate (OTFC) have been characterized. A range of doses may eventually be used in clinical practice. The goal of this study was to determine if the pharmacokinetics of OTFC are dose proportional for doses ranging from 200 to 1,600 microg. METHODS: Twelve healthy male volunteers were studied on four different occasions, receiving 200, 400, 800, and 1,600 microg OTFC in a double-blind, randomized protocol. Venous blood samples were collected at selected times during and after dosing for a 24-h period and assayed for fentanyl using a radioimmunoassay. Maximum concentration, time to maximum concentration, area under the curve, and elimination half-life were determined for each dose administered. In addition, respiratory rate, need for verbal prompting to breathe, and supplemental oxygen requirements were noted. RESULTS: Mean fentanyl concentration time curves were similarly shaped with increasing doses. Both peak concentrations and area under the curve increased linearly with an increase in dose, whereas time to reach peak serum concentrations did not vary significantly between doses. Except for the 200-microg dose, the apparent elimination half-life remained relatively constant (358-386 min). The incidence of low respiratory rate, supplemental oxygen requirement, and number of breathing prompts significantly increased with increasing doses. CONCLUSIONS: Oral transmucosal fentanyl citrate exhibits dose-proportional pharmacokinetics over the dose range of 200-1,600 microg.

The road to specialization.

This paper describes the history and current status of specialization within dental practice in the UK.

[Studies on the causative factors of cervical wedge-shaped defect of human teeth from three dimensions].

OBJECTIVE: To investigate causative factors of cervical wedge-shaped defect of human teeth and the significance of methods for measurement of the defect. METHODS: Experimental cervical defects on 9 pairs of premolars were created by cross-brushing, erosion, or fatigue of occlusion force separately or combinedly and measured in depth and area of profile as well as in volume. RESULTS: 1. Profile depth of defects caused by three factors separately showed no statistical difference, but the profile depth caused by combining factors was much more than that caused by each individual factor; 2. The hardness of enamel and dentin in defect area was lower than that in normal area of tooth samples; 3. Measurement from one-dimension (depth) and two-dimension (area) showed only low relation in profile depth, however, measured three-dimensionally (volume) there existed moderate relationship. CONCLUSION: For study of cervical defect, the profile depth is feasible provided that is a large sample group and without equipment for volume measuring; if the sample size is limited and there is sophiscated instrument for volume measuring, the 3-dimensional measurement is the most sensitive one.

Etiology and management of tooth wear: the association of drugs and medicaments.

Teeth are sometimes worn excessively by erosion (chemical damage), abrasion (physical damage) or attrition (wear between opposing teeth). The most important role of self-prescribed or physician-prescribed drugs is the management of conditions which cause regurgitation erosion.