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Over the years, the development of microfluidic devices has emerged as a promising platform for point-of-care analysis and diagnostics that covers different areas of application. This can be applied in various fields, such as chemistry and physics. This work carried out a prospective technological survey of microfluidic devices used for detecting heavy metals with paper as the main raw material. The search for patents and articles took place in different databases, using the keywords “microfluidic device AND heavy metal AND paper”. This topic has attracted attention in the academic world, as observed in Scopus, with the publication of 3.361 documents, with the main leaders being the China and United States. The number of patents published according to WIPO is 3.396 and they highlighted countries such as the United States and Australia. In Brazil, there is a growing interest in this area through the development and improvement of these devices. Ao longo dos anos, o desenvolvimento de dispositivos microfluídicos surgiu como uma plataforma promissora para análises e diagnósticos do tipo point-of-care que abrange diversas áreas de aplicação, por exemplo, a química e a física. Neste trabalho, realizou-se o levantamento prospectivo tecnológico de dispositivo microfluídicos utilizado para detecção de metais pesados, tendo o papel como matéria-prima principal. A execução das buscas de patentes e artigos ocorreu em diferentes bases de dados, utilizando as palavras-chave microfluidic device AND heavy metal AND paper. Essa temática tem atraído atenção no meio acadêmico, como observado no Scopus, com o número de publicações de 3.361 documentos, com os países líderes China e Estados Unidos, enquanto o número de patentes publicadas conforme o WIPO é de 3.396, destacando países como Estados Unidos e Austrália. No Brasil, há um crescente interesse nesse cenário por meio do desenvolvimento e do aperfeiçoamento do dispositivo.

Background In the Diagnostic and Statistical Manual of Mental Disorders-Fifth edition (DSM-5), the diagnostic criteria of intellectual disability (ID) include three domains of adaptive deficits: the conceptual, social and practical. Substantial intra-individual differences between domains can be considered an ID domain discrepancy. Method We explored the associations between ID domains, discrepancies and epilepsy in 189 adults (mean age = 47.9; SD = 15.6). Each DSM-5 ID domain was assessed separately, using subscales of the Vineland II for the social and practical domains, and psychological instruments, including intelligence tests, for the conceptual domain. A set of standardised criteria is proposed to identify an ID domain discrepancy. Results An ID domain discrepancy seemed to be present in about one-third of subjects and was particularly present in subjects with moderate ID (53.4%). Impairment in the social domain was most often the reason for the discrepancy. The presence of a discrepancy was significantly related to a focal (localised) epilepsy type (OR = 2.3, P = .028) and a mixed seizure type (OR = 1.4, P = .009). Epilepsy characteristics that are indicative of a more severe and refractory epilepsy, including various seizure types, a high seizure frequency, a combined epilepsy type (both focal and generalised epilepsy) and an early age at onset, were significantly related to more severe impairments in conceptual, social and practical adaptive behaviour (all P values

Significance: Current imaging paradigms for differential diagnosis of suspicious breast lesions suffer from high false positive rates that force patients to undergo unnecessary biopsies. Diffuse optical spectroscopic imaging (DOSI) noninvasively probes functional hemodynamic and compositional parameters in deep tissue and has been shown to be sensitive to contrast between normal and malignant tissues. Aim: DOSI methods are under investigation as an adjunct to mammography and ultrasound that could reduce false positive rates and unnecessary biopsies, particularly in radiographically dense breasts. Methods: We performed a retrospective analysis of 212 subjects with suspicious breast lesions who underwent DOSI imaging. Physiological tissue parameters were z-score normalized to the patient’s contralateral breast tissue and input to univariate logistic regression models to discriminate between malignant tumors and the surrounding normal tissue. The models were then used to differentiate malignant lesions from benign lesions. Results: Models incorporating several individual hemodynamic parameters were able to accurately distinguish malignant tumors from both the surrounding background tissue and benign lesions with area under the curve (AUC) ≥0.85. Z-score normalization improved the discriminatory ability and calibration of these predictive models relative to unnormalized or ratio-normalized data. Conclusions: Findings from a large subject population study show how DOSI data normalization that accounts for normal tissue heterogeneity and quantitative statistical regression approaches can be combined to improve the ability of DOSI to diagnose malignant lesions. This improved diagnostic accuracy, combined with the modality’s inherent logistical advantages of portability, low cost, and nonionizing radiation, could position DOSI as an effective adjunct modality that could be used to reduce the number of unnecessary invasive biopsies.

Significance: Particle field holography is a versatile technique to determine the size and distribution of moving or stationary particles in air or in a liquid without significant disturbance of the sample volume. Although this technique is applied in biological sample analysis, it is limited to small sample volumes, thus increasing the number of measurements per sample. In this work, we characterize the maximum achievable volume limit based on the specification of a given sensor to realize the development of a potentially low-cost, single-shot, large-volume holographic microscope.Aim: We present mathematical formulas that will aid in the design and development and improve the focusing speed for the numerical reconstruction of registered holograms in particle field holographic microscopes. Our proposed methodology has potential application in the detection of Schistosoma haematobium eggs in human urine samples.Approach: Using the Fraunhofer holography theory for opaque objects, we derived an exact formula for the maximum diffraction-limited volume for an in-line holographic setup. The proof-of-concept device built based on the derived formulas was experimentally validated with urine spiked with cultured Schistosoma haematobium eggs.Results: Results obtained show that for urine spiked with Schistosoma haematobium eggs, the volume thickness is limited to several millimeters due to scattering properties of the sample. The distances of the target particles could be estimated directly from the hologram fringes.Conclusion: The methodology proposed will aid in the development of large-volume holographic microscopes. (C) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License.

Significance: Processing and diagnosing a set of 12 prostate biopsies using conventional histology methods typically take at least one day. A rapid and accurate process performed while the patient is still on-site could significantly improve the patient’s quality of life. Aim: We develop and assess the feasibility of a one-hour-to-diagnosis (1Hr2Dx) method for processing and providing a preliminary diagnosis of a set of 12 prostate biopsies. Approach: We developed a fluorescence staining, optical clearing, and 3D open-top light-sheet microscopy workflow to enable 12 prostate needle core biopsies to be processed and diagnosed within an hour of receipt. We analyzed 44 biopsies by the 1Hr2Dx method, which does not consume tissue. The biopsies were then processed for routine, slide-based 2D histology. Three pathologists independently evaluated the 3D 1Hr2Dx and 2D slide-based datasets in a blinded, randomized fashion. Turnaround times were recorded, and the accuracy of our method was compared with gold-standard slide-based histology. Results: The average turnaround time for tissue processing, imaging, and diagnosis was 44.5 min. The sensitivity and specificity of 1Hr2Dx in diagnosing cancer were both >90%. Conclusions: The 1Hr2Dx method has the potential to improve patient care by providing an accurate preliminary diagnosis within an hour of biopsy.

Objective: We investigated the effectiveness of a self-help intervention named PERANTARA, which aims to improve adherence to diagnostic procedures among women with breast cancer (BC) symptoms to reduce the time to a definitive diagnosis. Methods: With a cluster randomized crossover design across four hospitals, PERANTARA and treatment as usual (TAU) or TAU only was provided at successive periods in a randomly determined order. The main outcome was the time between the first medical consultation and the definitive diagnosis. Secondary outcomes were BC knowledge, measured by the Breast Cancer Knowledge Test (BCKT); symptoms of anxiety and depression, measured by the Hospital Anxiety and Depression Scale (HADS); quality of life, measured by the World Health Organization Quality of Life-BREF (WHOQOL-BREF); and health status, measured by the EQ-5D-5L. A linear mixed model analysis was conducted to analyse the outcomes. Results: We recruited 132 women with BC symptoms from four hospitals; 67 participants were in the intervention group, and 65 participants were in the control group. PERANTARA reduced the time to definitive diagnosis by 13.3 days (M [SD]: 25.90 [23.20] in the intervention group vs 39.29 [35.10] in the control group; mean difference = −13.26, 95% CI = −24.51 to −2.00, P =.02). No significant difference was found between the groups in BC knowledge, symptoms of anxiety, depression, quality of life, or health status. Conclusions: PERANTARA reduced the time to definitive diagnosis among Indonesian women with BC symptoms. Psychoeducation may be an important addition to regular BC care to prevent undue delays in diagnostic procedures.

In human history, the paper has long been used as a platform to record and preserve information. However, over the decades, paper has found its application in Biomedical Sciences, too. Both paper-based microfluidic devices (μPADs) and paper-based cultures and scaffolds have shown immense potential to be used as a sensor as well as a supporting material for in vitro tissue engineering. μPADs can be used to perform low-cost and fast biomolecular assays at Point-Of-Care (POC). They are being used to detect various biomarkers like viral proteins, metabolites, oncogenes, and antigens; and conditions like Venous Thromboembolism (VTE). On the other hand, the paper has also been used to develop paper-based 3D cultures and scaffolds to test drugs, and monitor cytotoxic effects in vitro cell microenvironments and also as implantable tissues. In this review, we intend to enumerate the development in the field of μPADs, paper-based cell cultures, and paper-based scaffolds and their plethora of applications over the last decade.

OBJECTIVE: Even when medical treatments are limited, supporting patients' coping strategies could improve their quality of life. Greater understanding of patients' coping strategies, and influencing factors, can aid developing such support. We examined the prevalence of coping strategies and associated variables.METHODS: We used sociodemographic and baseline data from the ACTION trial, including measures of Denial, Acceptance, and Problem-focused coping (COPE; Brief COPE inventory), of patients with advanced cancer from six European countries. Clinicians provided clinical information. Linear mixed models with clustering at hospital level were used.RESULTS: Data from 675 patients with stage III/IV lung (342, 51%) or stage IV colorectal (333, 49%) cancer were used; mean age 66 (10 SD) years. Overall, patients scored low on Denial and high on Acceptance and Problem-focused coping. Older age was associated with higher scores on Denial than younger age (β = 0.05; CI[0.023; 0.074]), and patients from Italy (β = 1.57 CI[0.760; 2.388]) and Denmark (β = 1.82 CI[0.881; 2.750]) scored higher on Denial than patients in other countries.CONCLUSIONS: Patients with advanced cancer predominantly used Acceptance and Problem-focused coping, and Denial to a lesser extent. Since the studied coping strategies of patients with advanced cancer vary between subpopulations, we recommend taking these factors into account when developing tailored interventions to support patients' coping strategies.

Significance: Hyperspectral imaging (HSI) is an emerging optical technique that has a double function of spectroscopy and imaging. Aim: Near-infrared hyperspectral imaging (NIR-HSI) (900 to 1700 nm) with the help of chemometrics was investigated for gastric cancer diagnosis. Approach: Mean spectra and standard deviation of normal and cancerous pixels were extracted. Principal component analysis (PCA) was used to compress the dimension of hypercube data and select the optimal wavelengths. Moreover, spectral angle mapper (SAM) was utilized as chemometrics to discriminate gastric cancer from normal. Results: Major spectral difference of cancerous and normal gastric tissue was observed around 975, 1215, and 1450 nm by comparison. A total of six wavelengths (i.e., 975, 1075, 1215, 1275, 1390, and 1450 nm) were then selected as optimal wavelengths by PCA. The accuracy using SAM is up to 90% according to hematoxylin–eosin results. Conclusions: These results suggest that NIR-HSI has the potential as a cutting-edge optical diagnostic technique for gastric cancer diagnosis with suitable chemometrics.

Quasi-static ultrasound elastography (USE) is an imaging modality that measures deformation (i.e. strain) of tissue in response to an applied mechanical force. In USE, the strain modulus is traditionally obtained by deriving the displacement field estimated between a pair of radio-frequency data. In this work we propose a recurrent network architecture with convolutional long-short-term memory decoder blocks to improve displacement estimation and spatio-temporal continuity between time series ultrasound frames. The network is trained in an unsupervised way, by optimising a similarity metric between the reference and compressed image. Our training loss is also composed of a regularisation term that preserves displacement continuity by directly optimising the strain smoothness, and a temporal continuity term that enforces consistency between successive strain predictions. In addition, we propose an open-access in vivo database for quasi-static USE, which consists of radio-frequency data sequences captured on the arm of a human volunteer. Our results from numerical simulation and in vivo data suggest that our recurrent neural network can account for larger deformations, as compared with two other feed-forward neural networks. In all experiments, our recurrent network outperformed the state-of-the-art for both learning-based and optimisation-based methods, in terms of elastographic signal-to-noise ratio, strain consistency, and image similarity. Finally, our open-source code provides a 3D-slicer visualisation module that can be used to process ultrasound RF frames in real-time, at a rate of up to 20 frames per second, using a standard GPU.

Despite advances in intraoperative surgical imaging, reliable discrimination of critical tissue during surgery remains challenging. As a result, decisions with potentially life-changing consequences for patients are still based on the surgeon's subjective visual assessment. Hyperspectral imaging (HSI) provides a promising solution for objective intraoperative tissue characterisation, with the advantages of being non-contact, non-ionising and non-invasive. However, while its potential to aid surgical decision-making has been investigated for a range of applications, to date no real-time intraoperative HSI (iHSI) system has been presented that follows critical design considerations to ensure a satisfactory integration into the surgical workflow. By establishing functional and technical requirements of an intraoperative system for surgery, we present an iHSI system design that allows for real-time wide-field HSI and responsive surgical guidance in a highly constrained operating theatre. Two systems exploiting state-of-the-art industrial HSI cameras, respectively using linescan and snapshot imaging technology, were designed and investigated by performing assessments against established design criteria and ex vivo tissue experiments. Finally, we report the use of our real-time iHSI system in a clinical feasibility case study as part of a spinal fusion surgery. Our results demonstrate seamless integration into existing surgical workflows., Journal of Physics D: Applied Physics, 54 (29), ISSN:0022-3727, ISSN:1361-6463

Elastography imaging is a promising tool—in both research and clinical settings—for diagnosis, staging, and therapeutic treatments of various life-threatening diseases (including brain tumors, breast cancers, prostate cancers, and Alzheimer’s disease). Large variation in the physical (elastic) properties of tissue, from normal to diseased stages, enables highly sensitive characterization of pathophysiological states of the diseases. On the other hand, over the last decade or so, photoacoustic (PA) imaging—an imaging modality that combines the advantageous features of two separate imaging modalities, i.e., high spatial resolution and high contrast obtainable, respectively, from ultrasound- and optical-based modalities—has been emerging and widely studied. Recently, recovery of elastic properties of soft biological tissues—in addition to prior reported recovery of vital tissue physiological information (Hb, HbO2, SO, and total Hb), noninvasively and nondestructively, with unprecedented spatial resolution (μm) at penetration depth (cm)—has been reported. Studies demonstrating that combined recovery of mechanical tissue properties and physiological information—by a single (PA) imaging unit—pave a promising platform in clinical diagnosis and therapeutic treatments. We offer a comprehensive review of PA imaging technology, focusing on recent advances in relation to elastography. Our review draws out technological challenges pertaining to PA elastography (PAE) imaging, and viable approaches. Currently, PAE imaging is in the nurture stage of its development, where the technology is limited to qualitative study. The prevailing challenges (specifically, quantitative measurements) may be addressed in a similar way by which ultrasound elastography and optical coherence elastography were accredited for quantitative measurements.

International audience; The incidence of arbovirus infections has increased dramatically in recent decades, affecting hundreds of millions of people each year. The Togaviridae family includes the chikungunya virus (CHIKV), which is typically transmitted by Aedes mosquitoes and causes a wide range of symptoms from flu-like fever to severe arthralgia. Although conventional diagnostic tests can provide early diagnosis of CHIKV infections, access to these tests is often limited in developing countries. Consequently, there is an urgent need to develop efficient, affordable, simple, rapid, and robust diagnostic tools that can be used in point-of-care settings. Early diagnosis is crucial to improve patient management and to reduce the risk of complications. A glass-fiber laser-cut microfluidic device (paper-based analytical device [PAD]) was designed and evaluated in a proof of principle context, for the analysis of 30 µL of patient serum. Biological raw materials used for the functionalization of the PAD were first screened by MAC-ELISA (IgM capture enzyme-linked immunosorbent assay) for CHIKV Immunoglobulin M (IgM) capture and then evaluated on the PAD using various human samples. Compared with viral lysate traditionally used for chikungunya (CHIK) serology, CHIKV pseudo-particles (PPs) have proven to be powerful antigens for specific IgM capture. The PAD was able to detect CHIKV IgM in human sera in less than 10 minutes. Results obtained in patient sera showed a sensitivity of 70.6% and a specificity of around 98%. The PAD showed few cross-reactions with other tropical viral diseases. The PAD could help health workers in the early diagnosis of tropical diseases such as CHIK, which require specific management protocols in at-risk populations.

Infective endocarditis is a severe disease with high mortality. Despite a global trend towards an increase in staphylococcal aetiologies, in older patients and a decrease in viridans streptococci, we have observed in recent studies great epidemiologic disparities between countries. In order to evaluate these differences among Mediterranean countries, we performed a PubMed search of infective endocarditis case series for each country. Data were available for 13 of the 18 Mediterranean countries. Despite great differences in diagnostic strategies, we could classify countries into three groups. In northern countries, patients are older (>50 years old), have a high rate of prosthetic valves or cardiac electronic implantable devices and the main causative agent is Staphylococcus aureus. In southern countries, patients are younger (

Background The recent emergence of Chikungunya Virus (CHIKV) in the Americas constitutes a major public health problem on this continent, where the mosquito vector is widespread. The rapid diagnosis of suspected cases is essential for the monitoring and control of this ongoing outbreak. However, this requires reliable tools that are difficult to establish in areas without specialized laboratories. Objectives The aim was to evaluate the performances of serum samples spotted onto filter paper for molecular and serological diagnosis of Chikungunya infection. Study design Analyses were performed from frozen sera and serum spotted onto filter paper provided from 121 Chikungunya suspected cases collected at a biological laboratory on Saint-Martin Island. Results This approach performed well in comparisons with standard methods, with a sensitivity of 100% and a specificity of 93.6% for the combined technical approaches (RT-PCR and serological results). Comparisons of serum samples spotted onto filter paper and frozen samples showed a concordance rate of 94.8% in molecular tests and 98.2% in serological tests. Conclusions This simple sampling technique could overcome the problems of the lack of efficient CHIKV diagnosis tools in remote regions, providing good results regardless of the molecular or serological approach used. This simple filter paper-based method can be used to diagnose both chikungunya and dengue infections, as previously demonstrated following transport at ambient temperature to specialized laboratories. Given the set-up costs and high performance of this method, it could be recommended for the monitoring and control of Chikungunya virus expansion in the Americas and in other affected regions.

We investigated the effect that two common types of cationic polyelectrolytes used in papermaking might have on the performance of paper diagnostics using blood typing as an example. The results were analyzed in terms of red blood cells (RBC) retention and antibody–antigen specificity. Two questions were addressed: (1) can poly(amido-amine) epichlorohydrin (PAE) typically used for paper wet strength affect the diagnostic performance? (2) can high molecular weight cationic polyacrylamide (CPAM) employed as retention aid enhance or affect the selectivity and sensitivity of paper diagnostics? A series of paper varying in type of fibers and drying process were constructed with PAE and tested for blood typing performance. Residual PAE has no significant effect on blood typing paper diagnostics under normal conditions. Positives are unaffected with PAE, while negatives lose slight sharpness as some RBCs are unselectively retained. CPAM, the most common retention aid, can also be used to retain cells and biomolecules on paper. Paper towel was treated with CPAM solutions varying in polymer concentration and charge density and tested for blood typing. We found that CPAM dried on paper can retain RBC. CPAM affects the negative tests by retaining non-specifically individual RBC on fibers. RBC retention increases non-linearly with the CPAM charge density and concentration. As expected, wet CPAM retain RBCs at concentrations higher than 0.1 wt%. As paper diagnostics are becoming a reality, more realistic papers than the Whatman filter paper will be engineered. This study provides guidance on how best use the required polymeric wet-strength and retention agents.

Paper-based sensors are a new alternative technology for fabricating simple, low-cost, portable and disposable analytical devices for many application areas including clinical diagnosis, food quality control and environmental monitoring. The unique properties of paper which allow passive liquid transport and compatibility with chemicals/biochemicals are the main advantages of using paper as a sensing platform. Depending on the main goal to be achieved in paper-based sensors, the fabrication methods and the analysis techniques can be tuned to fulfill the needs of the end-user. Current paper-based sensors are focused on microfluidic delivery of solution to the detection site whereas more advanced designs involve complex 3-D geometries based on the same microfluidic principles. Although paper-based sensors are very promising, they still suffer from certain limitations such as accuracy and sensitivity. However, it is anticipated that in the future, with advances in fabrication and analytical techniques, that there will be more new and innovative developments in paper-based sensors. These sensors could better meet the current objectives of a viable low-cost and portable device in addition to offering high sensitivity and selectivity, and multiple analyte discrimination. This paper is a review of recent advances in paper-based sensors and covers the following topics: existing fabrication techniques, analytical methods and application areas. Finally, the present challenges and future outlooks are discussed.

This article describes a prototype system for quantifying bioassays, and for exchanging the results of the assays digitally with physicians located off-site. The system uses paper-based microfluidic devices for running multiple assays simultaneously, camera phones or portable scanners for digitizing the intensity of color associated with each colorimetric assay, and established communications infrastructure for transferring the digital information from the assay site to an off-site laboratory for analysis by a trained medical professional; the diagnosis then can be returned directly to the healthcare provider in the field. The microfluidic devices were fabricated in paper using photolithography, and were functionalized with reagents for colorimetric assays. The results of the assays were quantified by comparing the intensities of the color developed in each assay with those of calibration curves. An example of this system quantified clinically relevant concentrations of glucose and protein in artificial urine. The combination of patterned paper, a portable method for obtaining digital images, and a method for exchanging results of the assays with off-site diagnosticians offers new opportunities for inexpensive monitoring of health, especially in situations that require physicians to travel to patients (e.g., in the developing world, in emergency management, and during field operations by the military) to obtain diagnostic information that might be obtained more effectively by less valuable personnel.

Introduction In 2000–2004 there were, on average, 93 8 new cases of colorectal cancer (CRC) diagnosed per annum in Northern Ireland, accounting for 13.9% of all cancers. The two week “red flag” referral system aims to detect 90% of patients with CRC for prompt treatment. The aim of this study is to examine the impact of the “red flag” referral system on identification of patients with CRC, time to treatment and stage of disease. Methods A random sample of 200 patients referred via the “red flag” system was identified from the local cancer patient tracker database. Data pertaining to demographics, time to hospital appointment, appropriateness of referral and diagnosis were collected. For patients identified with CRC, the stage of disease and time to first definitive treatment were also documented. Results Of the 200 patients, 56% were female. The age range was 27–93 years. Eighty three percent were seen within 14 days of referral. Referrals adhered to the guidelines in 45% of cases. There were 4 pancreatic cancers, 1 endometrial cancer, 1 ovarian cancer and 1 myelodysplasia diagnosed. Three patients were diagnosed with CRC (1.5%). Of these, 1 was palliative and the remaining 2 commenced definitive management within 6 days of decision to treat. Conclusion The “red flag” referral system does not appear to be effective in identifying patients with CRC but did identify patients with other types of cancer. Less than half of the referrals adhered to the guidelines. A review of this system should be undertaken.

The collection of dried blood spots (DBS) on filter paper provides a powerful approach for the development of large-scale, population-based screening programs. DBS methods are particularly valuable in developing countries and isolated rural regions where resources are limited. Large numbers of field specimens can be economically collected and shipped to centralized reference laboratories for genetic and (or) serological analysis. Alternatively, the dried blood can be stored and used as an archival resource to rapidly establish the frequency and distribution of newly recognized mutations, confirm patient identity or track the origins and emergence of newly identified pathogens. In this report, we describe how PCR-based technologies are beginning to interface with international screening programmes for the diagnosis and genetic characterization of human immunodeficiency virus type 1 (HIV-1). In particular, we review recent progress using DBS specimens to resolve the HIV-1 infection status of neonates, monitor the genetic evolution of HIV-1 during early infancy and establish a sentinel surveillance system for the systematic monitoring of HIV-1 genetic variation in Asia.

Cryogenic transmission electron microscopy (cryo-EM) was used to explore the self-assembly of recombinant murine amelogenin (rM179) in vitro.Our cryo-EM data showed that amelogenin self-assembly is a strongly pH-dependent process. At pH 4.4 the main fraction of the protein exists in a monomeric form, although some peculiar structures consisting of chains of monomers were also observed. At pH 5.8 large nanospheres comprising ring-like structures ∼50 nm in diameter were the most abundant particle class. Similarly, at pH 8.0 amelogenins self-assembled into ring-like oligomers of different sizes, which subsequently assembled into nanospheres 15–20 nm in diameter. Furthermore, at pH 7.2, which is close to a physiological pH, branched chains of nanospheres were observed. Our results show that amelogenin assembly is a multistep hierarchical process and provides new insight into the control of enamel mineralization.

Contains fulltext : 52943.pdf (Publisher’s version ) (Closed access) BACKGROUND: Neurofilament (NF) proteins are major cytoskeletal constituents of neurons. Increased CSF NF levels may reflect neuronal degeneration. OBJECTIVE: To investigate the diagnostic value of CSF NF analysis to discriminate in relatively young dementia patients between frontotemporal lobe degeneration (FTLD) and early onset Alzheimer's disease (EAD; onset < or = 65 years of age), and in elderly dementia patients between dementia with Lewy bodies (DLB) and late onset AD (LAD; onset > 65 years of age). METHODS: In CSF of 28 FTLD, 37 EAD, 18 DLB and 33 LAD patients, and 26 control subjects, we analysed NF light chain (NFL), phosphorylated NF heavy chain (pNFH), amyloid beta42 protein (Abeta42), total tau and tau phosphorylated at threonine 181 (p-tau181). RESULTS: CSF NFL levels were higher in FTLD patients compared with EAD patients (p