The appropriateness of current UK training in acute internal medicine.

Doctors training in Acute Internal Medicine (AIM) need to provide evidence that they can effectively manage 20 'top' and 40 'other important' acute medical presentations. However, the presentations considered important in the AIM curriculum do not have an empirical evidence base. This study compared real-life presentations against those in the AIM curriculum. Data on all presentations to the acute medical service at The Royal Free Hospital, London, were collected retrospectively for five non-consecutive weeks and prospectively for one week. Five frequently encountered presentations viz: cough, nausea and vomiting, dizziness, hyperglycaemia and lethargy were not amongst those listed as 'top' or 'other important' in the AIM curriculum. Hence, demonstration of competency in these presentations is currently not an explicit requirement.

A set of systematic reviews to help reduce inappropriate prescribing to older people: study protocol.

BACKGROUND: Multimorbidity and polypharmacy are common in older people. Assessment tools or lists of criteria aimed at supporting prescription decisions for older people exist, but have often been based on expert opinion with insufficient consideration of the evidence available. The present paper describes the methods we are using to systematically review the existing evidence on the efficacy and safety of the most commonly prescribed drugs for older people in the management of their chronic medical conditions and to develop recommendations to reduce inappropriate prescriptions for incorporation into the Comprehensive Medication Review (CMR) tool developed by the PRIMA-eDS European project. METHODS: We selected the 20 most relevant drugs/drug classes in terms of prescription volumes and risk of hospitalisation for older people and the most relevant indications for the most common chronic conditions among older people and a total of 35 distinct drug-indication pairs were chosen. Based on clinical considerations we collapsed some indications together, reducing the 35 pairs to a final total of 22 separate systematic reviews (SR). A common methodology will be used for each individual SR, based on the methodological manuals of the Cochrane collaboration and the PRISMA statement for reporting systematic reviews. Our search strategy will have a staged approach where we initially search for systematic reviews and meta-analyses, but if relevant reviews are not found, then search for individual studies (controlled intervention and observational studies). Our pilot work and initial scoping of the literature suggested that very few, relevant individual trials or existing systematic reviews have researched or reported exclusively on older people. Therefore, sufficient data might not be available to perform meta-analysis but we will provide a narrative synthesis describing characteristics and findings of included studies. The collected evidence will be used to construct recommendations on when not to use or to discontinue a drug, or when to reduce its dose. Recommendations will be developed in team meetings using the GRADE methodology to reflect the strength of the recommendation and the quality of the evidence. Recommendations will be built into the CMR tool. DISCUSSION: This protocol has been prepared for a series of systematic reviews which will provide research-based evidence to develop recommendations to reduce inappropriate polypharmacy in older people as part of the CMR tool of the PRIMA-eDS project.

Effectiveness and safety of dipeptidyl peptidase 4 inhibitors in the management of type 2 diabetes in older adults: a systematic review and development of recommendations to reduce inappropriate prescribing.

BACKGROUND: Preventable drug-related hospital admissions can be associated with drugs used in diabetes and the benefits of strict diabetes control may not outweigh the risks, especially in older populations. The aim of this study was to look for evidence on risks and benefits of DPP-4 inhibitors in older adults and to use this evidence to develop recommendations for the electronic decision support tool of the PRIMA-eDS project. METHODS: Systematic review using a staged approach which searches for systematic reviews and meta-analyses first, then individual studies only if prior searches were inconclusive. The target population were older people (≥65 years old) with type 2 diabetes. We included studies reporting on the efficacy and/or safety of DPP-4 inhibitors for the management of type 2 diabetes. Studies were included irrespective of DPP-4 inhibitors prescribed as monotherapy or in combination with any other drug for the treatment of type 2 diabetes. The target intervention was DPP-4 inhibitors compared to placebo, no treatment, other drugs to treat type 2 diabetes or a non-pharmacological intervention. RESULTS: Thirty studies (reported in 33 publications) were included: 1 meta-analysis, 17 intervention studies and 12 observational studies. Sixteen studies were focused on older adults and 14 studies reported subgroup analyses in participants ≥65, ≥70, or ≥75 years. Comorbidities were reported by 26 studies and frailty or functional status by one study. There were conflicting findings regarding the effectiveness of DPP-4 inhibitors in older adults. In general, DPP-4 inhibitors showed similar or better safety than placebo and other antidiabetic drugs. However, these safety data are mainly based on short-term outcomes like hypoglycaemia in studies with HbA1c control levels recommended for younger people. One recommendation was developed advising clinicians to reconsider the use of DPP-4 inhibitors for the management of type 2 diabetes in older adults with HbA1c <8.5% because of scarce data on clinically relevant benefits of their use. Twenty-two of the included studies were funded by pharmaceutical companies and authored or co-authored by employees of the sponsor. CONCLUSIONS: Other than the surrogate endpoint of improved glycaemic control, data on clinically relevant benefits of DPP-4 inhibitors in the treatment of type 2 diabetes mellitus in older adults is scarce. DPP-4 inhibitors might have a lower risk of hypoglycaemia compared to other antidiabetic drugs but data show conflicting findings for long-term benefits. Further studies are needed that evaluate the risks and benefits of DPP-4 inhibitors for the management of type 2 diabetes mellitus in older adults, using clinically relevant outcomes and including representative samples of older adults with information on their frailty status and comorbidities. Studies are also needed that are independent of pharmaceutical company involvement.

Efficacy of Codeine When Added to Paracetamol (Acetaminophen) and Ibuprofen for Relief of Postoperative Pain After Surgical Removal of Impacted Third Molars: A Double-Blinded Randomized Control Trial.

PURPOSE: The use of opioids in combination with nonopioids is common practice for acute pain management after third molar surgery. One such combination is paracetamol, ibuprofen, and codeine. The authors assessed the efficacy of codeine when added to a regimen of paracetamol and ibuprofen for pain relief after third molar surgery. MATERIALS AND METHODS: This study was a randomized, double-blinded, placebo-controlled trial conducted in patients undergoing the surgical removal of at least 1 impacted mandibular third molar requiring bone removal. Participants were randomly allocated to a control group (paracetamol 1,000 mg and ibuprofen 400 mg) or an intervention group (paracetamol 1,000 mg, ibuprofen 400 mg, and codeine 60 mg). All participants were treated under intravenous sedation and using identical surgical conditions and technique. Postoperative pain was assessed using the visual analog scale (VAS) every 3 hours (while awake) for the first 48 hours after surgery. Pain was globally assessed using a questionnaire on day 3 after surgery. RESULTS: There were 131 participants (36% men; control group, n = 67; intervention group, n = 64). Baseline characteristics were similar for the 2 groups. Data were analyzed using a modified intention-to-treat analysis and, for this, a linear mixed model was used. The model showed that the baseline VAS score was associated with subsequent VAS scores and that, with each 3-hour period, the VAS score increased by an average of 0.08. The treatment effect was not statistically meaningful, indicating there was no difference in recorded pain levels between the 2 groups during the first 48 hours after mandibular third molar surgery. Similarly, the 2 groups did not differ in their global ratings of postoperative pain. CONCLUSION: Codeine 60 mg added to a regimen of paracetamol 1,000 mg and ibuprofen 400 mg does not improve analgesia after third molar surgery.

Relationship between cardiac diffusion tensor imaging parameters and anthropometrics in healthy volunteers.

BACKGROUND: In vivo cardiac diffusion tensor imaging (cDTI) is uniquely capable of interrogating laminar myocardial dynamics non-invasively. A comprehensive dataset of quantative parameters and comparison with subject anthropometrics is required. METHODS: cDTI was performed at 3T with a diffusion weighted STEAM sequence. Data was acquired from the mid left ventricle in 43 subjects during the systolic and diastolic pauses. Global and regional values were determined for fractional anisotropy (FA), mean diffusivity (MD), helix angle gradient (HAg, degrees/%depth) and the secondary eigenvector angulation (E2A). Regression analysis was performed between global values and subject anthropometrics. RESULTS: All cDTI parameters displayed regional heterogeneity. The RR interval had a significant, but clinically small effect on systolic values for FA, HAg and E2A. Male sex and increasing left ventricular end diastolic volume were associated with increased systolic HAg. Diastolic HAg and systolic E2A were both directly related to left ventricular mass and body surface area. There was an inverse relationship between E2A mobility and both age and ejection fraction. CONCLUSIONS: Future interpretations of quantitative cDTI data should take into account anthropometric variations observed with patient age, body surface area and left ventricular measurements. Further work determining the impact of technical factors such as strain and SNR is required.

A panel of nine cerebrospinal fluid biomarkers may identify patients with atypical parkinsonian syndromes.

BACKGROUND: Patients presenting with parkinsonian syndromes share many clinical features, which can make diagnosis difficult. This is important as atypical parkinsonian syndromes (APSs) such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and corticobasal syndrome (CBS) carry a poor prognosis, compared with patients with Parkinson's disease (PD). In addition, there is overlap between APS and dementia diseases, such as Alzheimer's disease (AD) and frontotemporal dementia (FTD). OBJECTIVE: To use a panel of cerebrospinal fluid (CSF) biomarkers to differentiate patients with APS from PD and dementia. METHODS: A prospective cohort of 160 patients and 30 control participants were recruited from a single specialist centre. Patients were clinically diagnosed according to current consensus criteria. CSF samples were obtained from patients with clinical diagnoses of PD (n=31), PSP (n=33), CBS (n=14), MSA (n=31), AD (n=26) and FTD (n=16). Healthy, elderly participants (n=30) were included as controls. Total τ (t-τ), phosphorylated τ (p-τ), ß-amyloid 1-42 (Aß42), neurofilament light chain (NFL), α-synuclein (α-syn), amyloid precursor protein soluble metabolites α and ß (soluble amyloid precursor protein (sAPP)α, sAPPß) and two neuroinflammatory markers (monocyte chemoattractant protein-1 and YKL-40) were measured in CSF. A reverse stepwise regression analysis and the false discovery rate procedure were used. RESULTS: CSF NFL (p<0.001), sAPPα (p<0.001) and a-syn (p=0.003) independently predicted diagnosis of PD versus APS. Together, these nine biomarkers could differentiate patients with PD from APS with an area under the curve of 0.95 and subtypes of APS from one another. There was good discriminatory power between parkinsonian groups, dementia disorders and healthy controls. CONCLUSIONS: A panel of nine CSF biomarkers was able to differentiate APS from patients with PD and dementia. This may have important clinical utility in improving diagnostic accuracy, allowing better prognostication and earlier access to potential disease-modifying therapies.

Characteristics of progressive supranuclear palsy presenting with corticobasal syndrome: a cortical variant.

AIMS: Since the first description of the classical presentation of progressive supranuclear palsy (PSP) in 1963, now known as Richardson's syndrome (PSP-RS), several distinct clinical syndromes have been associated with PSP-tau pathology. Like other neurodegenerative disorders, the severity and distribution of phosphorylated tau pathology are closely associated with the clinical heterogeneity of PSP variants. PSP with corticobasal syndrome presentation (PSP-CBS) was reported to have more tau load in the mid-frontal and inferior-parietal cortices than in PSP-RS. However, it is uncertain if differences exist in the distribution of tau pathology in other brain regions or if the overall tau load is increased in the brains of PSP-CBS. METHODS: We sought to compare the clinical and pathological features of PSP-CBS and PSP-RS including quantitative assessment of tau load in 15 cortical, basal ganglia and cerebellar regions. RESULTS: In addition to the similar age of onset and disease duration, we demonstrated that the overall severity of tau pathology was the same between PSP-CBS and PSP-RS. We identified that there was a shift of tau burden towards the cortical regions away from the basal ganglia; supporting the notion that PSP-CBS is a 'cortical' PSP variant. PSP-CBS also had less severe neuronal loss in the dorsolateral and ventrolateral subregions of the substantia nigra and more severe microglial response in the corticospinal tract than in PSP-RS; however, neuronal loss in subthalamic nucleus was equally severe in both groups. CONCLUSIONS: A better understanding of the factors that influence the selective pathological vulnerability in different PSP variants will provide further insights into the neurodegenerative process underlying tauopathies.

Identification of aero-allergen sensitization in children seeking treatment for bronchial asthma at a tertiary care hospital for children in Sri Lanka.

OBJECTIVES: Despite a significant rise in asthma globally as well as in Sri Lanka, data regarding allergen sensitization patterns and other risk factors for asthma are not available. Therefore, we set out to determine the allergen sensitization patterns in children with asthma in Sri Lanka. METHODS: Skin prick testing for common indoor aeroallergens (cockroach, cat, dog, house dust mite, moulds) were carried out in 156 children with bronchial asthma at Lady Ridgeway Hospital for Children. RESULTS: 49.1% of the patients were sensitized to at least one allergen and 6.4% were sensitized to three or more allergens. Of the children 37.8% tested positive to house dust mite, 23.7% to cockroach, 5.8% to indoor moulds, 12.2% to cats and 8.9% to dogs. Allergen sensitization was significantly less in children aged four years or younger than in older children (p<0.0001). A family history of asthma or allergic rhinitis (AR) was a significant risk factor (p<0.0001) for allergen sensitization (OR 10.9, 95% CI 3.9 to 30.1). Frequency of symptoms was significantly higher in those who used firewood alone compared to those who used other fuels (OR 2.5, 95% CI 1.1 to 5.8). CONCLUSIONS: Sensitization to aero-allergens was seen in a majority of children with asthma. Sensitization was significantly more in children above 4 years of age. Patients with more frequent symptoms and with AR were more likely to be sensitized to allergens.

Knowledge of diabetes among type 2 diabetes patients attending a primary health care clinic in Sri Lanka.

Patients' knowledge about their illness is considered important in controlling diabetes and preventing complications. A descriptive, cross-sectional study was conducted among patients attending the diabetes clinic of a primary care level hospital in Moratuwa, Sri Lanka. During a 1-month period in 2009 all consenting patients diagnosed with type 2 diabetes who had been attending the clinic for more than 3 months were included in the study. Using an interviewer administered, structured questionnaire 150 patients (135 females, 15 males) answered 25 questions about diabetes knowledge (scored x4 to give score range 0-100). A majority of patients (70.0%) had a good score (> 65) on the knowledge test but critical gaps in knowledge were revealed, especially regarding knowledge about symptoms of poor control and importance of regular follow-up. Although patients with longer duration of diabetes had higher mean knowledge scores, they also had higher fasting blood glucose levels. Education programmes are needed to address critical gaps in patients' knowledge.

Mesial temporal astrocyte tau pathology in the MRC-CFAS ageing brain cohort.

BACKGROUND: Glial tau pathology is seen in certain tauopathies and in ageing. We determined its frequency in ageing mesial temporal lobe and its relationship to other tau pathologies in the MRC-CFAS population-representative neuropathology cohort. METHODS: Mesial temporal lobe, including hippocampus, amygdala, entorhinal cortex and white matter, was examined using immunohistochemistry with the AT8 antibody to phospho-tau and RD3 and RD4 antibodies to 3R and 4R tau isoforms. Gallyas silver stain was used to detect fibrillar aggregates. RESULTS: Thorn-shaped astrocytes (TSA), positive with AT8, RD4 and Gallyas, were present in 49% of cases. They were particularly prevalent in subpial, periventricular and white matter perivascular locations and were less frequent in grey matter. Coiled bodies were seen in 18.8%. TSA were not related to Braak neurofibrillary tangle or hippocampal tangle pathology stages. TSA in grey matter were associated with coiled bodies (p = 0.011) and argyrophilic grains (p = 0.048), which were identified in 11.5% of cases. They did not correlate with dementia. CONCLUSIONS: Astrocyte tau pathology is common in the ageing mesial temporal lobe. Its formation is independent of Alzheimer-type pathology. It is a 4R tauopathy, which may form part of a mesial temporal age-related 4R tauopathy that includes oligodendroglial tau and argyrophilic grains.

A novel approach to managing circumferential entrapment of a child's tongue within a plastic lid.

BACKGROUND: The increased popularity of reusable drinking bottles may have safety implications when used by children. This paper discusses the lessons learnt from managing two cases of children presenting to our ENT department who required surgical intervention for complications arising from their use. CASE REPORT: This paper presents a case series of two five-year-old children who attended the emergency department with circumferential entrapment of their tongue within plastic drinking bottle lids of similar design. The unique anaesthetic and surgical challenges surrounding these cases are discussed. CONCLUSION: These represent the only reported cases of circumferential entrapment of the tongue by a foreign body requiring general anaesthesia where orotracheal intubation was contraindicated. A creative general anaesthetic approach was taken using ketamine and Optiflow high-flow nasal oxygen therapy. A reproducible surgical technique using powered cutting instruments is also discussed.

Complicated Dengue Fever and Its Treatment Dilemmas: A Single-Center Experience in Sri Lanka.

Dengue is an arboviral infection that affects humanscausing significant morbidity and mortality in tropical countries. Our first patient who had diabetes presented with shock and was managed as dengue hemorrhagic fever with superadded sepsis which required noradrenalin plus broad-spectrum intravenous antibiotics. The second patient developed severe bradycardia during the ascending limb of the critical phase with hemodynamic stability, which recovered on discharge. Third patient presented with severe and rapid leaking; we used intravenous albumin as an alternative colloid with good outcome. The fourth patient was a pregnant mother at term, and she went into spontaneous labor during the latter half of the critical phase. The fifth patient developed dengue hemorrhagic fever complicated with probable haemophagocytic lymphohistiocytosis. She was treated with intravenous steroids andimmunoglobulin, yet succumbed on day 7. Conclusion. Dengue is an extremely challenging and dynamic disease, which can lead to many unusual complications.A high index of suspicion is key to diagnose and treat promptly.

Renal, Cardiac, and Autonomic Effects of Catheter-Based Renal Denervation in Ovine Heart Failure.

[Figure: see text].

Hippocampal tau pathology is related to neuroanatomical connections: an ageing population-based study.

Deposits of abnormally phosphorylated tau protein are found in numerous neurodegenerative disorders; the 'tauopathies', which include Alzheimer's and Pick's diseases, but tau pathology is also found in the ageing brain. Variation in tau pathology in brain ageing and its relationship to development of tauopathies and cognitive impairment remains unclear. We aimed to determine the extent and pattern of spread of tau pathology in the hippocampus, a susceptible region important in dementia and milder states of memory impairment, using hippocampal samples from the elderly population-based Medical Research Council Cognitive Function and Ageing Study neuropathology cohort. Tau deposition was assessed in hippocampal anatomical sub-regions using the AT8 antibody to phosphorylated tau and isoform-specific antibodies to 3 and 4-repeat tau (RD3 and RD4). Abeta pathology was also assessed. In this population sample, which includes the full ageing spectrum from individuals with no cognitive impairment to those with dementia satisfying clinico-pathology criteria for Alzheimer's disease, we have demonstrated a high prevalence at death of tau pathology. AT8, Abeta, RD3 and RD4 showed similar regional distribution and increased RD3 was noted in late-stage ghost tangles. Abeta was shown to be a poor explanatory variable for tau pathology. Tau deposition progressed in a hierarchical manner. Hippocampal input regions and projection zones (such as lateral entorhinal cortex, CA1/subiculum border and outer molecular layer of dentate) were initially affected, with anterograde progression though the hippocampal circuitry. Six hippocampal tau anatomical stages were defined, each linking projectionally to their adjacent stages, suggesting spread of tau malfunction through neuroanatomical pathways in hippocampal ageing. These stages were significantly associated with dementia, and may provide a clinically useful tool in the clinico-pathological assessment of dementia and mild cognitive impairment.

Curcumin loaded zinc oxide nanoparticles for activity-enhanced antibacterial and anticancer applications.

Zinc oxide nanoparticles and curcumin have been shown to be excellent antimicrobial agents and promising anticancer agents, both on their own as well as in combination. Together, they have potential as alternatives/supplements to antibiotics and traditional anticancer drugs. In this study, different morphologies of zinc oxide-grafted curcumin nanocomposites (ZNP-Cs) were synthesized and characterized using SEM, TGA, FTIR, XRD and UV-vis spectrophotometry. Antimicrobial assays were conducted against both Gram negative and Gram-positive bacterial stains. Spherical ZnO-curcumin nanoparticles (SZNP-Cs) and rod-shaped ZnO-curcumin nanoparticles showed the most promising activity against tested bacterial strains. The inhibition zones for these curcumin-loaded ZnO nanocomposites were consistently larger than their bare counterparts or pure curcumin, revealing an additve effect between the ZnO and curcumin components. The potential anticancer activity of the synthesized nanocomposites was studied on the rhabdomyosarcoma RD cell line via MTT assay, while their cytotoxic effects were tested against human embryonic kidney cells using the resazurin assay. SZNP-Cs exhibited the best balance between the two, showing the lowest toxicity against healthy cells and good anticancer activity. The results of this investigation demonstrate that the nanomatrix synthesized can act as an effective, additively-enhanced combination delivery/therapeutic agent, holding promise for anticancer therapy and other biomedical applications.

Risk of blood splashes to the eye during surgery.

BACKGROUND: With the advent of a new infectious era involving the HIV and hepatitis B and C viruses, concern has arisen about transmission of these viruses through ocular blood splashes during surgery. The purpose of the study was to determine the risk of ocular blood splashes to surgeons and their assistants during surgery. METHOD: Surgeons and assistants in several surgical disciplines were requested to wear facemasks with a transparent plastic visor. The visors were collected postoperatively and inspected for macroscopic and microscopic blood splashes. RESULTS: Fifty-nine per cent of the surgeons and assistants refused to wear facemasks with a visor. The incidence of blood splashes in those who participated was 45%. There was a trend for blood splashes to be more common during major surgery and during elective surgery. Surgeons and assistants were subject to similar risk. CONCLUSION: This study confirms the significant risk of ocular blood splashes during surgery, while also suggesting that both surgeons and assistants lack appreciation of the risk.

Effect of networked hybridized nanoparticle reinforcement on the thermal conductivity and mechanical properties of natural rubber composites.

Thermal conductivity of natural rubber (NR) was enhanced by incorporating novel conductive hybrid nanofillers, namely polyaniline grafted carbon black (PANI/CB) nanoparticles and carbon black nanoparticles linked with carbon microfiber (CF/CB) composites. The PANI/CB hybrid fillers were synthesized using an in situ method, where aniline monomers were initially adsorbed onto carbon black spherical domains and, afterwards, it was polymerized in the presence of an oxidizer. Final rubber composites were prepared through melt mixing, where PANI/CB and CF/CB filler loading was kept at 40 parts per hundred of rubber (phr). The thermal conductivity values of the rubber composites with CF/CB (20 : 20) and PANI/CB (20 : 20) yield were 0.45 W m-1 K-1 and 0.31 W m-1 K-1, respectively and the thermal conductivity improved significantly compared to the control (0.25 W m-1 K-1) sample. The higher thermal conductivity values of CF/CB and PANI/CB incorporated composites suggest that the generated networked structure of CF and PANI nanofibers with CB nanoparticles has immensely contributed to enhancing the heat dissipation compared to that of the neat CB rubber composite. Scanning electron micrographs (SEM) confirmed the attachment of the synthesized PANI onto the spherical CB nanoparticles and interconnected morphology of CF/CB and PANI/CB hybrid fillers. The synthesized PANI/CB hybrid filler was further characterized using Fourier-transform infrared (FTIR) spectroscopy to evaluate the chemical properties. Furthermore, thermogravimetric analysis revealed the higher thermal stability of CF/CB (20 : 20) and PANI/CB (20 : 20) composites compared to the control. Moreover, the addition of CF/CB (20 : 20) and PANI/CB (20 : 20) improved the mechanical properties such as ultimate tensile strength, modulus at break, resilience and abrasion resistance significantly and well above the minimum required standard mechanical parameters in the tyre industry. These reinforced composites show great potential to be used as heat dissipating rubber composites in the tyre industry.

Facile and low-cost synthesis of pure hematite (α-Fe2O3) nanoparticles from naturally occurring laterites and their superior adsorption capability towards acid-dyes.

Hematite nanoparticles have a broad range of outstanding applications such as in wastewater treatment, electrolytic studies, and photoelectrochemical and superparamagnetic applications. Therefore, the development of facile and novel methods to synthesize hematite nanoparticles using low-cost raw materials is an important and timely requirement. In this study, we have developed a facile economical route to synthesize hematite nanoparticles, directly from the naturally occurring material laterite. Laterite is a rock that is rich in Fe and Al with extensive distribution in large mineable quantities in many countries around the world, though not yet utilized for major industrial applications. In this method, ferric ions in the laterite were leached out using acid and the solution obtained was hydrolyzed with slow-release hydroxyl ions which were acquired by aqueous decomposition of urea. The resulted precursor was calcined to obtain hematite nanoparticles. Characterization data shows that the final product is comprised of spherical hematite nanoparticles with a narrow particle size vs. frequency distribution with an average particle diameter of 35 nm. The synthesized product has a purity of over 98%. Furthermore, the synthesized nanoparticles show an excellent adsorption percentage as high as 70%, even when the initial dye concentration in water is 5000 ppm and the amount of material is minimal, towards acid dyes which are excessively used in textile based industries. Such acid dyes are a threat to the environment when they are released into water bodies by industries in massive quantities. Therefore synthesized hematite nanoparticles are ideal to treat dye wastewater in industrial effluents because such nanoparticles are low cost and economical, and the synthesis procedure is rather facile and effective.

Expression of BRI2 mRNA and protein in normal human brain and familial British dementia: its relevance to the pathogenesis of disease.

INTRODUCTION: Two different disease-specific mutations in the BRI2 gene, situated on chromosome 13, have been identified as giving rise to familial British dementia (FBD) and familial Danish dementia (FDD). Each mutation results in extension of the open reading frame generating the disease-specific precursor proteins which are cleaved by furin-like proteolysis releasing the amyloidogenic C-terminal peptides ABri and ADan in FBD and FDD, respectively. MATERIAL AND METHODS: To understand the mechanism of the formation of amyloid lesions in FBD, we studied the origin of the precursor proteins and furin in the human brain. We used control brains, cases of sporadic Alzheimer's disease (AD), variant AD with cotton wool plaques and FBD to study BRI2 mRNA expression using in situ hybridization. Furin and BRI2 protein expression was investigated using Western blotting and immunohistochemistry. RESULTS: BRI2 mRNA and BRI2 protein are widely expressed primarily by neurones and glia and are deposited in the amyloid lesions in FBD. They were, however, not expressed by cerebrovascular components. Furin expression showed a similar pattern except that it was also present in cerebrovascular smooth muscle cells. CONCLUSIONS: These findings suggest that neurones and glia and are a major source of BRI2 protein and that in FBD, the mutated precursor protein may undergo furin cleavage within neurones to produce the amyloid peptide ABri. The failure to demonstrate BRI2 in blood vessels under the conditions tested suggests that vascular amyloid peptide production does not contribute significantly to cerebral amyloid angiopathy (CAA) in FBD and FDD, lending indirect support to the drainage hypothesis of CAA.