Sorbent-modified biodegradation studies of the biocidal cationic surfactant cetylpyridinium chloride.

Biodegradability studies for the cationic surfactant cetylpyridinium chloride (CPC) are hampered by inhibitory effects on inoculum at prescribed test concentrations (10-20 mg organic carbon/L). In this study, we used 14C labeled CPC in the 28 d Headspace Test (OECD 310) and demonstrated that CPC was readily biodegradable (10->60% mineralization within a 10 day window) at test concentrations 0.006-0.3 mg/L with CPC as single substrate. Biodegradation efficiency was comparable over this concentration range. CPC inhibited degradation at 1 mg/L and completely suppressed inoculum activity at 3 mg/L. In an extensive sorbent modified biodegradation study we evaluated the balance between CPC bioaccessibility and toxicity. A non-inhibitory concentration of 0.1 mg/L CPC was readily biodegradable with 83% sorbed to SiO2, while biodegradation was slower when 96% was sorbed. SiO2 mitigated inhibitory effects of 1 mg/L CPC, reaching >60% biodegradation within 28 d; inhibitory effects were also mitigated by addition of commercial clay powder (illite) but this was primarily reflected by a reduced lag phase. At 10 mg/L CPC SiO2 was still able to mitigate inhibitory effects, but bioaccessibility seemed limited as only 20% biodegradation was reached. Illite limited bioaccessibility more strongly and was not able to sustain biodegradation at 10 mg/L CPC.

A service evaluation of specialist nurse telephone follow-up of bowel cancer patients after surgery.

INTRODUCTION: the NHS Long Term Plan has called for a reduction in the number of outpatient appointments to reduce pressure on hospital services and increase ease of access for patients. This article presents a service evaluation of an innovative, nurse-led telephone follow-up service for a group of elective bowel cancer patients following surgery. METHODS: the records of patients who underwent surgery over a 2-year period were accessed to determine the number of telephone follow-ups and other investigations. This was used to model the potential cost saving for commissioners against traditional clinic follow-up. Patient satisfaction was assessed by the European Organisation for Research and Treatment of Cancer questionnaire on Outpatient Satisfaction in 30 patients. RESULTS: feedback on the service was overwhelmingly positive, with patients praising the care received from the specialist nurses, but also commenting on increased continuity of care, ease of access and convenience. The service also potentially creates significant savings for commissioners as the agreed tariff for nurse telephone follow-up is significantly less than the outpatient tariff. DISCUSSION: this innovative follow-up system is well liked by patients and should provide savings for commissioners. The hospital also benefits from an increase in capacity to see new or more unwell patients, and a reduction in carbon emissions. Such a service, however, is dependent on people, and although it has functioned effectively in this department for approximately 20 years, it would only be generalisable to other units if staff had appropriate expertise.

A service evaluation of specialist nurse telephone follow-up of bowel cancer patients after surgery.

INTRODUCTION: the NHS Long Term Plan has called for a reduction in the number of outpatient appointments to reduce pressure on hospital services and increase ease of access for patients. This article presents a service evaluation of an innovative, nurse-led telephone follow-up service for a group of elective bowel cancer patients following surgery. METHODS: the records of patients who underwent surgery over a 2-year period were accessed to determine the number of telephone follow-ups and other investigations. This was used to model the potential cost saving for commissioners against traditional clinic follow-up. Patient satisfaction was assessed by the European Organisation for Research and Treatment of Cancer questionnaire on Outpatient Satisfaction in 30 patients. RESULTS: feedback on the service was overwhelmingly positive, with patients praising the care received from the specialist nurses, but also commenting on increased continuity of care, ease of access and convenience. The service also potentially creates significant savings for commissioners as the agreed tariff for nurse telephone follow-up is significantly less than the outpatient tariff. DISCUSSION: this innovative follow-up system is well liked by patients and should provide savings for commissioners. The hospital also benefits from an increase in capacity to see new or more unwell patients, and a reduction in carbon emissions. Such a service, however, is dependent on people, and although it has functioned effectively in this department for approximately 20 years, it would only be generalisable to other units if staff had appropriate expertise.

X-ray diffraction evidence for myosin-troponin connections and tropomyosin movement during stretch activation of insect flight muscle.

Stretch activation is important in the mechanical properties of vertebrate cardiac muscle and essential to the flight muscles of most insects. Despite decades of investigation, the underlying molecular mechanism of stretch activation is unknown. We investigated the role of recently observed connections between myosin and troponin, called "troponin bridges," by analyzing real-time X-ray diffraction "movies" from sinusoidally stretch-activated Lethocerus muscles. Observed changes in X-ray reflections arising from myosin heads, actin filaments, troponin, and tropomyosin were consistent with the hypothesis that troponin bridges are the key agent of mechanical signal transduction. The time-resolved sequence of molecular changes suggests a mechanism for stretch activation, in which troponin bridges mechanically tug tropomyosin aside to relieve tropomyosin's steric blocking of myosin-actin binding. This enables subsequent force production, with cross-bridge targeting further enhanced by stretch-induced lattice compression and thick-filament twisting. Similar linkages may operate in other muscle systems, such as mammalian cardiac muscle, where stretch activation is thought to aid in cardiac ejection.

Loss of MTBP expression is associated with reduced survival in a biomarker-defined subset of patients with squamous cell carcinoma of the head and neck.

BACKGROUND: Recent genetic studies have implicated p53 mutation as a significant risk factor for therapeutic failure in squamous cell carcinoma of the head and neck (SCCHN). However, in a recent meta-analysis in the literature of p53 from major anatomical subsites (larynx, oral cavity, oropharynx/hypopharynx), associations between patient survival and p53 status were ambiguous. METHODS: The authors examined a cohort of SCCHNs using a previously developed biomarker combination that likely predicts p53 status based on p53/MDM2 expression levels determined by immunohistochemistry (IHC). In addition, the authors generated and validated an antibody to MTBP (an MDM2 binding protein that alters p53/MDM2 homeostasis and may contribute to metastatic suppression) and have incorporated data for MTBP expression into the current analyses. RESULTS: Analysis of expression data for p53 and MDM2 in 198 SCCHN patient samples revealed that the biomarker combination p53 + ve/MDM2-low (likely indicative of p53 mutation) was significantly associated with reduced overall survival (log-rank P = .035) and was an independent prognostic factor (P = .013; HR, 1.705; 95% CI, 1.12-2.60); thus, these data were compatible with earlier genetic analyses. By using IHC for p53 and MDM2 to dichotomize patients, the authors found that loss of MTBP expression was significantly associated with reduced survival (log-rank P = .004) and was an independent prognostic factor (P = .004; HR, 2.78; 95% CI, 1.39-5.54) in p53 + ve/MDM2-low patients. CONCLUSIONS: These results represent the first examination of MTBP expression in human tissues and provide evidence for a p53 status-dependent role for MTBP in suppressing disease progression in SCCHN patients as well as confirming a role for p53 pathway function in delaying disease progression.

Myosin head orientation: a structural determinant for the Frank-Starling relationship.

The cellular mechanism underlying the Frank-Starling law of the heart is myofilament length-dependent activation. The mechanism(s) whereby sarcomeres detect changes in length and translate this into increased sensitivity to activating calcium has been elusive. Small-angle X-ray diffraction studies have revealed that the intact myofilament lattice undergoes numerous structural changes upon an increase in sarcomere length (SL): lattice spacing and the I(1,1)/I(1,0) intensity ratio decreases, whereas the M3 meridional reflection intensity (I(M3)) increases, concomitant with increases in diastolic and systolic force. Using a short (∼10 ms) X-ray exposure just before electrical stimulation, we were able to obtain detailed structural information regarding the effects of external osmotic compression (with mannitol) and obtain SL on thin intact electrically stimulated isolated rat right ventricular trabeculae. We show that over the same incremental increases in SL, the relative changes in systolic force track more closely to the relative changes in myosin head orientation (as reported by I(M3)) than to the relative changes in lattice spacing. We conclude that myosin head orientation before activation determines myocardial sarcomere activation levels and that this may be the dominant mechanism for length-dependent activation.

Molecular dynamics of cyclically contracting insect flight muscle in vivo.

Flight in insects--which constitute the largest group of species in the animal kingdom--is powered by specialized muscles located within the thorax. In most insects each contraction is triggered not by a motor neuron spike but by mechanical stretch imposed by antagonistic muscles. Whereas 'stretch activation' and its reciprocal phenomenon 'shortening deactivation' are observed to varying extents in all striated muscles, both are particularly prominent in the indirect flight muscles of insects. Here we show changes in thick-filament structure and actin-myosin interactions in living, flying Drosophila with the use of synchrotron small-angle X-ray diffraction. To elicit stable flight behaviour and permit the capture of images at specific phases within the 5-ms wingbeat cycle, we tethered flies within a visual flight simulator. We recorded images of 340 micros duration every 625 micros to create an eight-frame diffraction movie, with each frame reflecting the instantaneous structure of the contractile apparatus. These time-resolved measurements of molecular-level structure provide new insight into the unique ability of insect flight muscle to generate elevated power at high frequency.

A near-peer teaching program designed, developed and delivered exclusively by recent medical graduates for final year medical students sitting the final objective structured clinical examination (OSCE).

BACKGROUND: The General Medical Council states that teaching doctors and students is important for the care of patients. Our aim was to deliver a structured teaching program to final year medical students, evaluate the efficacy of teaching given by junior doctors and review the pertinent literature. METHODS: We developed a revision package for final year medical students sitting the Objective Structured Clinical Examination (OSCE). The package was created and delivered exclusively by recent medical graduates and consisted of lectures and small group seminars covering the core areas of medicine and surgery, with a focus on specific OSCE station examples. Students were asked to complete a feedback questionnaire during and immediately after the program. RESULTS: One hundred and eighteen completed feedback questionnaires were analysed. All participants stated that the content covered was relevant to their revision. 73.2% stated that junior doctors delivered teaching that is comparable to that of consultant - led teaching. 97.9% stated the revision course had a positive influence on their learning. CONCLUSIONS: Our study showed that recent medical graduates are able to create and deliver a structured, formal revision program and provide a unique perspective to exam preparation that was very well received by our student cohort. The role of junior doctors teaching medical students in a formal structured environment is very valuable and should be encouraged.

Application of seven different clay types in sorbent-modified biodegradability studies with cationic biocides.

The cationic surfactants cetyltrimethylammonium bromide (CTAB) and cetylpyridinium chloride (CPC) can exert inhibitory effects on micro-organisms responsible for their biodegradation. However, under environmentally relevant exposure scenarios the presence of and sorption to organic and inorganic matter can lead to significant reduction of inhibitory effects. In our studies we investigated silica gel and seven clays as inert sorbents to mitigate these inhibitory effects in a 28 day manometric respirometry biodegradation test. CTAB was not inhibitory to the used inoculum, but we did observe that seven out of eight sorbents increased maximum attainable biodegradation, and four out of eight decreased the lag phase. The strongly inhibitory effect of CPC was successfully mitigated by most sorbents, with five out of eight allowing >50% biodegradation within 28 days. Results further indicate that bioaccessibility of the sorbed fractions in the stirred manometric test systems was higher than in calmly shaken headspace test systems. Bioaccessibility might also be limited depending on characteristics of test chemical and sorbent type, with montmorillonite and bentonite apparently providing the lowest level of bioaccessibility with CPC. Clay sorbents can thus be used as environmentally relevant sorbents to mitigate potential inhibitory effects of test chemicals, but factors that impede bioaccessibility should be considered. In addition to apparently increased bioaccessibility due to stirring, the automated manometric respirometry test systems give valuable and highly cost-effective insights into lag phase and biodegradation kinetics; information that is especially relevant for test chemicals of gradual biodegradability.

Structure of flexible filamentous plant viruses.

Flexible filamentous viruses make up a large fraction of the known plant viruses, but in comparison with those of other viruses, very little is known about their structures. We have used fiber diffraction, cryo-electron microscopy, and scanning transmission electron microscopy to determine the symmetry of a potyvirus, soybean mosaic virus; to confirm the symmetry of a potexvirus, potato virus X; and to determine the low-resolution structures of both viruses. We conclude that these viruses and, by implication, most or all flexible filamentous plant viruses share a common coat protein fold and helical symmetry, with slightly less than 9 subunits per helical turn.

Toxicity mitigation and bioaccessibility of the cationic surfactant cetyltrimethylammonium bromide in a sorbent-modified biodegradation study.

Biodegradation potential of cationic surfactants may be hampered by inhibition of inoculum at concentrations required to accurately measure inorganic carbon. At >0.3 mg/L cetyltrimethylammonium bromide (CTAB) negatively impacted degradation of the reference compound aniline. We used silicon dioxide (SiO2) and illite as inorganic sorbents to mitigate toxicity of CTAB by lowering freely dissolved concentrations. In an OECD Headspace Test we tested whether 16.8 mg/L CTAB was readily biodegradable in presence of two concentrations of SiO2 and illite. SiO2 adsorbed 85% and 98% CTAB, resulting in concentrations of 2.5 and 0.34 mg/L, mineralized to CO2 >60% within 16 and 23 d, respectively. With 89% and 99% sorbed to illite, 60% mineralization was reached within 9 and 23 d, respectively. However, higher sorbent concentrations increased time needed to reach >60% mineralization. Thus, desorption kinetics likely decreased bioaccessibility. It is therefore essential to determine appropriate concentrations of mitigating sorbents to render a Headspace Test based on carbon analysis suitable to determine ready biodegradability of compounds which might inhibit inoculum. This would avoid use of expensive radiolabeled compounds. However, high sorbent concentrations can reduce bioaccessibility and limit degradation kinetics, particularly for relatively toxic substances that require strong mitigation.

Low temperature traps myosin motors of mammalian muscle in a refractory state that prevents activation.

Myosin motors in the thick filament of resting striated (skeletal and cardiac) muscle are trapped in an OFF state, in which the motors are packed in helical tracks on the filament surface, inhibiting their interactions with actin and utilization of ATP. To investigate the structural changes induced in the thick filament of mammalian skeletal muscle by changes in temperature, we collected x-ray diffraction patterns from the fast skeletal muscle extensor digitorum longus of the mouse in the temperature range from near physiological (35°C) to 10°C, in which the maximal isometric force (T 0) shows a threefold decrease. In resting muscle, x-ray reflections signaling the OFF state of the thick filament indicate that cooling produces a progressive disruption of the OFF state with motors moving away from the ordered helical tracks on the surface of the thick filament. We find that the number of myosin motors in the OFF state at 10°C is half of that at 35°C. At T 0, changes in the x-ray signals that report the fraction and conformation of actin-attached motors can be explained if the threefold decrease in force associated with lowering temperature is due not only to a decrease in the force-generating transition in the actin-attached motors but also to a twofold decrease in the number of such motors. Thus, lowering the temperature reduces to the same extent the fraction of motors in the OFF state at rest and the fraction of motors attached to actin at T 0, suggesting that motors that leave the OFF state accumulate in a disordered refractory state that makes them unavailable for interaction with actin upon stimulation. This regulatory effect of temperature on the thick filament of mammalian skeletal muscle could represent an energetically convenient mechanism for hibernating animals.

The myosin filament superlattice in the flight muscles of flies: A-band lattice optimisation for stretch-activation?

Low-angle X-ray diffraction patterns from relaxed fruitfly (Drosophila) flight muscle recorded on the BioCat beamline at the Argonne Advanced Photon Source (APS) show many features similar to such patterns from the "classic" insect flight muscle in Lethocerus, the giant water bug, but there is a characteristically different pattern of sampling of the myosin filament layer-lines, which indicates the presence of a superlattice of myosin filaments in the Drosophila A-band. We show from analysis of the structure factor for this lattice that the sampling pattern is exactly as expected if adjacent four-stranded myosin filaments, of repeat 116 nm, are axially shifted in the hexagonal A-band lattice by one-third of the 14.5 nm axial spacing between crowns of myosin heads. In addition, electron micrographs of Drosophila and other flies (e.g. the house fly (Musca) and the flesh fly (Sarcophaga)) combined with image processing confirm that the same A-band superlattice occurs in all of these flies; it may be a general property of the Diptera. The different A-band organisation in flies compared with Lethocerus, which operates at a much lower wing beat frequency (approximately 30 Hz) and requires a warm-up period, may be a way of optimising the myosin and actin filament geometry needed both for stretch activation at the higher wing beat frequencies (50 Hz to 1000 Hz) of flies and their need for a rapid escape response.

Detection of functional ligand-binding events using synchrotron x-ray scattering.

Small-molecule ligands that change the structure of a protein are likely to affect its function, whereas those causing no structural change are less likely to be functional. Wide-angle x-ray scattering (WAXS) can be easily carried out on proteins and small molecules in solution in the absence of chemical tags or derivatives. The authors demonstrate that WAXS is a sensitive probe of ligand binding to proteins in solution and can distinguish between nonfunctional and productive binding. Furthermore, similar ligand-binding modes translate into similar scattering patterns. This approach has high potential as a novel, generic, low-throughput assay for functional ligand binding.

Glass ionomer cements: a review of composition, chemistry, and biocompatibility as a dental and medical implant material.

Glass ionomer cements are a group of materials based on the acid/base reaction between poly(alkenoic) acid and an ion-leachable silicate glass. The material was developed in dentistry as a tooth restorative material that released fluoride ions over an extended time, bonded to tooth structure, and was very biocompatible. Its use in dentistry was initially limited by its slow setting time and lack of strength; however, modern formulations of the material have yielded materials with properties that are clinically useful in dentistry. Its biocompatibility, osteoconductive behavior, and ability to bond to bone and metals have generated interest in the material for medical applications. Glass ionomer cements in medicine have been used as bone cements, implants to replace ossicular bones of the inner ear, as well as other craniofacial implants. The early release of fluoride and aluminum ions and release of polyacids have been implicated in tissue biocompatibility in medical use. Additional material development is necessary to optimize its properties for use in medicine. This article reviews the literature written on the composition, chemistry, fluoride release, biocompatibility, and medical uses of glass ionomer cements.

Vitallium.

Vitallium is a base metal alloy that has been used in dentistry and medicine since 1929. This article will focus on the historical perspectives of Vitallium and include the dental and medical applications used today. The physical and chemical properties of Vitallium will be discussed, with particular emphasis on the biocompatibility of the metal. Finally, the future uses of Vitallium will be examined, as will the potential dangers in fabricating prostheses using this base metal alloy.

Unreliable medical information on birth certificates.

OBJECTIVE: To compare selected maternal, obstetric and newborn medical information on live birth certificates to medical record abstracted data. STUDY DESIGN: The Florida Department of Health provided a computer tape containing the Hillsborough County Florida live birth certificate data for July 1, 1992, through December 31, 1996. This information was compared to selected maternal, obstetric and newborn medical data abstracted from the hospital records of women who delivered in that county. RESULTS: Three hospitals provided care for 75% (44,654) of all deliveries in the county in the study period. There were no differences in age, race, gravidity or parity of patients between the data sets. There was no concurrence between the number of patients on the state-compiled birth certificate data and the medical record data in 8 maternal medical complications, 5 complications of labor and delivery, 3 obstetric procedures, 3 abnormal neonatal conditions or 7 congenital anomalies from any hospitals. There was no difference between the three hospitals in the incidence of mismatches. CONCLUSION: The medical information on the birth certificates from this county was discrepant from that abstracted directly from the patients' medical records. Caution is required in drawing conclusions from these data sets.

Visual failure in the elderly and dysphagia.

A 91-year-old man presented with a history of acute dysphagia. Clinical examination found reduced oxygen saturations and lung basal crepitations. Blood tests revealed mild anaemia, leukocytosis and acute renal failure. Chest X-ray demonstrated two oesophageal foreign bodies (FBs) and consolidation at the left lung base. Dysphagia resolved following the removal of two coins at oesophagogastroduodenoscopy, the man did not recall ingesting coins. His coin ingestion was attributed to poor visual acquity and he was referred for eye examination and advised to keep coins separate from food and medication. Children and the aged are likely to swallow FBs; causes of ingestion include reduced ability to chew and/or distinguish between objects. Most FBs pass spontaneously, however those that become stuck are likely to impact in the oesophagus. It is important to consider visual acuity for both compliance with medication and to prevent ingestion of FBs.

Isolated lower limb medium-vessel vasculitis: a new entity?

A 47-year-old female was referred with bilateral ischaemic lesions affecting her toes with associated gangrene. Systemic examination was normal and her medical history was unremarkable. Close examination of the hands revealed splinter haemorrhages. Her feet were dusky in colour and the toes were dark and weeping, each becoming gangrenous, with erythema around the metatarsal phalangeal joint. Dorsalis pedis and posterior tibial pulses were intact with strong Doppler signals. Investigations for surgical pathology and malignancy were all negative as were routine blood tests and tests for autoimmune and viral markers. Vasculitis was diagnosed when her toes showed improvement with steroids, however, attempts to reduce the steroid dose were unsuccessful and azathioprine was introduced. Despite immunosuppression and immunomodulators, her toes deteriorated and were amputated. Histology revealed findings consistent with a medium-vessel vasculitis which antineutrophil cytoplasmic antibody was negative. A similar vasculitis has not been formally reported in the literature.