Margin Status and Local Recurrence in Phyllodes Tumours of the Breast: A Canadian Series.

BACKGROUND: Phyllodes tumours of the breast are rare fibroepithelial neoplasms with a propensity for recurrence. While surgical excision remains the standard of care, the optimal margin width is an area of active investigation. Recent studies have questioned the necessity for wide, local excision. METHODS: We conducted a retrospective, cohort study of patients with phyllodes tumours treated at our institution between 2003 and 2021. Demographic, histopathological, and recurrence data were captured; malignant phyllodes were excluded. Cox proportional hazard models were used to identify covariates associated with local recurrence. RESULTS: Of 187 patients with phyllodes tumours, 82.9% (n = 155) were classified as benign while 17.1% (n = 32) were borderline. Initial surgical margins were positive in 26.2% (n = 49), < 2 mm in 50.8% (n = 95), and ≥ 2 mm in 23% (n = 43) patients. Among patients with positive margins, 61.2% (n = 30) underwent margin revision. At a median follow-up of 2.9 years, the recurrence rate was 3.7%. On univariate analysis, only a positive margin at the time of initial surgery and not margin width was significantly associated with a higher rate of disease recurrence (hazard ratio [HR] 9.52, 95% confidence interval [CI] 1.85-49.2), as was a size greater than 4 cm on preoperative imaging (HR 10.78, 95% CI 0.97-120.1). Revision of an initially positive margin was not significantly associated with decreased local recurrence (p = 1). CONCLUSIONS: In this large cohort of benign and borderline phyllodes tumours, positive resection margins and not margin width at the initial surgery were associated with a increased recurrence. Individualization of decisions regarding margin reexcision is important.

Long-term outcome of paediatric anti-N-methyl-D-aspartate receptor encephalitis.

AIM: To study long-term clinical and cognitive outcomes of patients with anti-N-methyl-d-aspartate receptor encephalitis (NMDAR-E), an acute autoimmune neurological disease with severe acute presentations. METHOD: In this French multicentre retrospective observational cohort study, patients no older than 18 years with a follow-up of at least 2 years were included. Data from clinical and cognitive assessments were collected. RESULTS: Eighty-one patients were included (57 females, 24 males; median age 10 years 7 months [range 1-18 years], median follow-up 40 months [range 25-53 months]). At last follow-up, 35 patients (45%) had cognitive impairment, 48 (70%) had academic difficulties, and 65 (92%) needed rehabilitation. Seventy-one patients (88%) had a modified Rankin Scale score of no more than 2. A higher number of symptoms at diagnosis was associated with cognitive impairment (p = 0.01), while an abnormal electroencephalogram at diagnosis increased the risk of academic difficulties (p = 0.03). INTERPRETATION: Although most children with NMDAR-E seemed to recover from motor disabilities, more than 45% had cognitive and academic difficulties. The initial severity of symptoms seems to have an impact on cognition and academic performances. WHAT THIS PAPER ADDS: Forty-five per cent of patients had cognitive impairment at ≥2 years diagnosis of anti-N-methyl-d-aspartate receptor encephalitis (NMDAR-E). Seventy per cent of patients had academic difficulties at ≥2 years diagnosis of NMDAR-E. Ninety-two per cent of patients needed rehabilitative care at ≥2 years diagnosis of NMDAR-E. A high number of symptoms at diagnosis were associated with cognitive impairment.

Electrochemical Peptide-Based Sensors for Foodborne Pathogens Detection.

Food safety and quality control pose serious issues to food industry and public health domains, in general, with direct effects on consumers. Any physical, chemical, or biological unexpected or unidentified food constituent may exhibit harmful effects on people and animals from mild to severe reactions. According to the World Health Organization (WHO), unsafe foodstuffs are especially dangerous for infants, young children, elderly, and chronic patients. It is imperative to continuously develop new technologies to detect foodborne pathogens and contaminants in order to aid the strengthening of healthcare and economic systems. In recent years, peptide-based sensors gained much attention in the field of food research as an alternative to immuno-, apta-, or DNA-based sensors. This review presents an overview of the electrochemical biosensors using peptides as molecular bio-recognition elements published mainly in the last decade, highlighting their possible application for rapid, non-destructive, and in situ analysis of food samples. Comparison with peptide-based optical and piezoelectrical sensors in terms of analytical performance is presented. Methods of foodstuffs pretreatment are also discussed.

Electrochemical Fingerprints of Illicit Drugs on Graphene and Multi-Walled Carbon Nanotubes.

Illicit drugs use and abuse remains an increasing challenge for worldwide authorities and, therefore, it is important to have accurate methods to detect them in seized samples, biological fluids and wastewaters. They are recently classified as the latest group of emerging pollutants as their consumption increased tremendously in recent years. Nanomaterials have gained much attention over the last decade in the development of sensors for a myriad of applications. The applicability of these nanomaterials, functionalized or not, significantly increases and it is therefore highly suitable for use in the detection of illicit drugs. We have assessed the suitability of various nanoplatforms, such as graphene (GPH), multi-walled carbon nanotubes (MWCNTs), gold nanoparticles (AuNPs) and platinum nanoparticles (PtNPs) for the electrochemical detection of illicit drugs. GPH and MWCNTs were chosen as the most suitable platforms and cocaine, 3,4-methylendioxymethamfetamine (MDMA), 3-methylmethcathinone (MMC) and α-pyrrolidinovalerophenone (PVP) were tested. Due to the hydrophobicity of the nanomaterials-based platforms which led to low signals, two strategies were followed namely, pretreatment of the electrodes in sulfuric acid by cyclic voltammetry and addition of Tween 20 to the detection buffer. Both strategies led to an increase in the oxidation signal of illicit drugs. Binary mixtures of illicit drugs with common adulterants found in street samples were also investigated. The proposed strategies allowed the sensitive detection of illicit drugs in the presence of most adulterants. The suitability of the proposed sensors for the detection of illicit drugs in spiked wastewaters was finally assessed.

SARS-CoV-2, multiple sclerosis, and focal deficit in a postpartum woman: A case report.

SARS-CoV-2 infections raise many practical concerns in a woman with multiple sclerosis (MS) during the perinatal period. On the other hand, the impact of COVID-19 on patients with MS and disease-modifying therapies (DMTs) is unknown. We report on a female patient who was treated with interferon beta 1a (IFNB-1a) for many years for relapsing-remitting multiple sclerosis (RRMS) until December 2018. She developed COVID 19 infection in April 2020, after giving birth to a healthy baby girl, five weeks before. She developed a mild right hemiparesis 2 weeks later, without cold symptoms. On admission, PCR for SARS-CoV-2 was positive, and she received antivirals and corticotherapy. One month later, specific IgG and IgM antibodies were negative. The patient did not develop immunity to COVID-19 infection. This report raises several problems. The focal deficit could be a real relapse or a pseudo-relapse due to SARS-CoV-2 and postpartum patient vulnerability. The treatment options in this particular case raise many challenges. The absence of antibodies after a SARS-CoV-2 infection raises a big question over the acquired immunity, the increased risk of reinfection, and the subsequent evolution of MS. The standard of care for a woman with MS and COVID-19 infection during the postpartum period must be explored and more precise recommendations must be established in the future.

Tackling the Problem of Sensing Commonly Abused Drugs Through Nanomaterials and (Bio)Recognition Approaches.

We summarize herein the literature in the last decade, involving the use of nanomaterials and various (bio)recognition elements, such as antibodies, aptamers and molecularly imprinted polymers, for the development of sensitive and selective (bio)sensors for illicit drugs with a focus on electrochemical transduction systems. The use and abuse of illicit drugs remains an increasing challenge for worldwide authorities and, therefore, it is important to have accurate methods to detect them in seized samples, biological fluids and wastewaters. They are recently classified as the latest group of "emerging pollutants," as their consumption has increased tremendously in recent years. Nanomaterials, antibodies, aptamers and molecularly imprinted polymers have gained much attention over the last decade in the development of (bio)sensors for a myriad of applications. The applicability of these (nano)materials, functionalized or not, has significantly increased, and are therefore highly suitable for use in the detection of drugs. Lately, such functionalized nanoscale materials have assisted in the detection of illicit drugs fingerprints, providing large surface area, functional groups and unique properties that facilitate sensitive and selective sensing. The review discusses the types of commonly abused drugs and their toxicological implications, classification of functionalized nanomaterials (graphene, carbon nanotubes), their fabrication, and their application on real samples in different fields of forensic science. Biosensors for drugs of abuse from the last decade's literature are then exemplified. It also offers insights into the prospects and challenges of bringing the functionalized nanobased technology to the end user in the laboratories or in-field.

Vaccination in multiple sclerosis - Challenging practices (Review).

Infections are an ever-present problem in the medical community, even more so for patients with multiple sclerosis (MS), for whom these infections have been linked to relapses and neurological disabilities. Even though it was believed that MS can be caused by an infection, research does not support this theory. MS is a chronic inflammatory disease considered to be autoimmune. Vaccination is proven to be one of the most effective means to prevent infections, but still it is surrounded by controversy in the general populations, as well as in the MS group. Vaccines are generally considered safe for MS patients. The exceptions from this, which turn into contraindications, are a medical history of allergic reactions to one of the vaccine components and immunosuppressed patients in the particular case of live vaccines. Given the presumed autoimmunity of the disease, some medication for MS is immunosuppressive and any live vaccine should be administered before starting treatment. Although there is still confusion regarding this subject, the current guidelines have clearer recommendations about vaccinations in MS patients and especially in treated MS patients.

Electrochemical analysis of speedball-like polydrug samples.

Increasing global production, trafficking and consumption of drugs of abuse is an emerging threat to people's health and safety. Electrochemical approaches have been proved to be useful for on-site analysis of drugs of abuse. However, less attention has been focused on the analysis of polydrug samples, even though these samples pose severe health concerns, especially when stimulants and depressants are combined, as is the case of speedball, a mixture of cocaine and heroin. In this work, we provide solutions for the selective detection of cocaine (stimulant) in polydrug samples adulterated with heroin and codeine (depressants). The presence of either one of these compounds in cocaine street samples leads to an overlap with the cocaine signal in square-wave voltammetry measurements at unmodified carbon screen-printed electrodes, leading to inconclusive screening results in the field. The provided solutions to this problem consist of two parallel approaches: (i) cathodic pretreatment of the carbon screen-printed electrode surface prior to measurement under both alkaline and neutral conditions and (ii) electropolymerization of orthophenylenediamine on graphene modified carbon screen-printed electrodes prior to measurement under neutral conditions. Both strategies allow simultaneous detection of cocaine and heroin in speedball samples as well as simultaneous detection of cocaine and codeine. Implementing these strategies in portable devices holds great potential for significantly improved accuracy of on-site cocaine screening in polydrug samples.

Fatigue, depression, and quality of life in children with multiple sclerosis: a comparative study with other demyelinating diseases.

AIM: To evaluate fatigue, depression, and quality of life (QoL) of children with multiple sclerosis and compare to other acute demyelinating syndromes (ADS). METHOD: Children followed in the National Referral Centre of rare inflammatory brain and spinal diseases were included in this study. The Expanded Disability Status Scale, the fatigue severity scale, the Multiscore Depression Inventory for Children, and the Pediatric Quality of Life Inventory were used for evaluation. RESULTS: Thirty-seven children (23 females, 14 males) were included in this study. Multiple sclerosis was diagnosed in 26 children and ADS in 11 children. Although not significant, severe fatigue was less frequently reported by patients with multiple sclerosis than children with ADS (44% vs 63%, p=0.2). Depression was reported more often in the multiple sclerosis group compared to the ADS group (24% vs 18%, p=0.6). Concerning the QoL in patients with multiple sclerosis, both parents and children reported poor emotional and school functioning. Physical and social functioning were rated as being good in both groups, and was significantly higher in the children's group (p=0.007). INTERPRETATION: This study highlights the importance of fatigue and depression in children with ADS and particularly in paediatric onset multiple sclerosis. Moreover, difficulties in school and emotional functioning were the main concerns for parents and children in the multiple sclerosis group which need to be taken in account during their care and treatment proposal. WHAT THIS PAPER ADDS: Invisible signs such as fatigue and depression affect all forms of acute demyelinating syndromes (ADS) in children. Depression seems to be higher in children with multiple sclerosis than with other forms of ADS. Fatigue seems to be lower in children with multiple sclerosis than with other forms of ADS. Children with multiple sclerosis and their parents are most concerned with emotional and academic functioning.

FATIGA, DEPRESIÓN Y CALIDAD DE VIDA EN NIÑOS CON ESCLEROSIS MÚLTIPLE: UN ESTUDIO COMPARATIVO CON OTRAS ENFERMEDADES DESMIELINIZANTES: OBJETIVO: evaluar fatiga, depresión y calidad de vida (CDV) de niños con esclerosis múltiple y comparar con otros síndromes desmielinizantes agudos (SDA). METODO: Se incluyeron en el estudio los niños seguidos en el centro de referencia de enfermedades espinales y cerebrales inflamatorias raras. Se usaron para la evaluación la Escala de Estado de Discapacidad Expandida, la escala de severidad de fatiga, el inventario de puntaje múltiple de depresión para niños, y el inventario de calidad de vida pediátrico. RESULTADOS: Se incluyeron en este estudio 37 niños (23 niñas, 14 niños). Se diagnosticó esclerosis múltiple en 26 niños y SDA en 11 niños. Aunque no fue significativo, la fatiga se reportó en menor frecuencia en pacientes con esclerosis múltiple que en niños con SDA (44% vs 63%, p=0,2). Se reporto con más frecuencia depresión en el grupo de esclerosis múltiple en comparación con el grupo de SDA (24% vs 18%, p=0,6). En lo que concierne a la calidad de vida en pacientes con esclerosis múltiple, tanto los padres como los niños reportaron funciones emocionales y escolares disminuidas. Las funciones físicas y sociales fueron puntuadas como buenas en ambos grupos, y fue significativamente más alta en el grupo de los niños. (p=0,007). INTERPRETACION: este estudio resalta la importancia de la fatiga y la depresión en niños con SDA y particularmente con el inicio infantil de esclerosis múltiple. Además, las dificultades en la escuela y el funcionamiento emocional fueron las principales preocupaciones de los padres y los niños en el grupo de esclerosis múltiple que deben tenerse en cuenta durante el planeamiento de atención de la salud y tratamiento.

FADIGA, DEPRESSÃO E QUALIDADE DE VIDA EM CRIANÇAS COM ESCLEROSE MÚLTIPLA: UM ESTUDO COMPARATIVO COM OUTRAS DOENÇAS DESMIELINIZANTES: OBJETIVO: Avaliar fadiga, depressão e qualidade de vida (QV) de crianças com esclerose múltipla, e comparar com outras síndromes desmielinizantes agudas (SDA). MÉTODO: Crianças acompanhadas em um centro de referência nacional de doenças inflamatórias cerebrais e espinhais raras foram incluídas no estudo. A Escala Expandidade de Estado da Deficiência, a escala de severidade da fadiga, o Inventário multiescore de depressão para crianças, e o Inventário Pediátrico de Qualidade de Vida foram usados na avaliação. RESULTADOS: Trinta e sete crianças (23 do sexo feminino, 14 do sexo masculino) foram incluídas neste estudo. A esclerose múltipla foi diagnosticada em 26 crianças e SDA em 11 crianças. Embora não significativa, a fadiga severa foi menos frequentemente reportada por pacientes com esclerose múltipla do que em crianças com SDA (44% vs 63%, p=0,2). A depressão foi reportada mais frequentemente no grupo com esclerose múltipla comparado ao grupo com SDA. (24% vs 18%, p=0,6). Com relação à QV em pacientes com esclerose múltipla, pais e crianças reportaram pobre funcionamento emocional e escolar. O funcionamento físico e social foram pontuados como bons em ambos os grupos, sendo significativamente maior no grupo de crianças (p=0,007). INTERPRETAÇÃO: Este estudo destaca a importância da fadiga e depressão em crianças com SDA e particularmente nos casos de esclerose múltipla de início pediátrico. Além disso, dificuldades no funcionamento escolar e emocional foram as principais preocupações dos pais e crianças no grupo com esclerose múltipla, o que deve ser levado em conta durante a proposta de cuidado e tratamento.

Unraveling the Mechanisms Behind the Complete Suppression of Cocaine Electrochemical Signals by Chlorpromazine, Promethazine, Procaine, and Dextromethorphan.

The present work investigates the challenges accompanied by the electrochemical cocaine detection in physiological conditions (pH 7) in the presence of chlorpromazine, promethazine, procaine, and dextromethorphan, frequently used cutting agents in cocaine street samples. The problem translates into the absence of the cocaine oxidation signal (signal suppression) when in a mixture with one of these compounds, leading to false negative results. Although a solution to this problem was provided through earlier experiments of our group, the mechanisms behind the suppression are now fundamentally investigated via electrochemical and liquid chromatography quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS) strategies. The latter was used to confirm the passivation of the electrodes due to their interaction with promethazine and chlorpromazine. Electron transfer mechanisms were further identified via linear sweep voltammetry. Next, adsorption experiments were performed on the graphite screen printed electrodes both with and without potential assistance in order to confirm if the suppression of the cocaine signals is due to passivation induced by the cutting agents or their oxidized products. The proposed strategies allowed us to identify the mechanisms of cocaine suppression for each cutting agent mentioned. Suppression due to procaine and dextromethorphan is caused by fouling of the electrode surface by their oxidized forms, while for chlorpromazine and promethazine the suppression of the cocaine signal is related to the strong adsorption of these (nonoxidized) cutting agents onto the graphite electrode surface. These findings provide fundamental insights in possible suppression and other interfering mechanisms using electrochemistry in general not only in the drug detection sector.

Electrochemical sensing of cocaine in real samples based on electrodeposited biomimetic affinity ligands.

A selective electrochemical sensor for direct detection of cocaine was developed based on molecularly imprinted polymers electropolymerized onto graphene-modified electrodes. Palladium nanoparticles were integrated in the sensing layer for the benefit of enhancing the communication between the imprinted sites and the electrode and improving their homogeneous distribution. The molecularly imprinted polymer was synthesized by cyclic voltammetry using p-aminobenzoic acid as a high affinity monomer selected by computational modeling, and cocaine as a template molecule. Experimental parameters related to the electrochemical deposition of palladium nanoparticles, pH, composition of the electropolymerization mixture, extraction and rebinding conditions were studied and optimized. Under optimized conditions, the oxidation peak current varied linearly with cocaine concentration in the range of 100-500 µM, with a detection limit of 50 µM (RSD 0.71%, n = 3). The molecularly imprinted sensor was able to detect cocaine in saliva and river water with good recoveries after sample pretreatment and was successfully applied for screening real street samples for cocaine.

Electrochemical Strategies for Adulterated Heroin Samples.

Electrochemical strategies to selectively detect heroin in street samples without the use of complicated electrode modifications were developed for the first time. For this purpose, heroin, mixing agents (adulterants, cutting agent, and impurities), and their binary mixtures were subjected to square wave voltammetry measurements at bare graphite electrodes at pH 7.0 and pH 12.0, in order to elucidate the unique electrochemical fingerprint of heroin and mixing agents as well as possible interferences or reciprocal influences. Adjusting the pH from pH 7.0 to pH 12.0 allowed a more accurate detection of heroin in the presence of most common mixing agents. Furthermore, the benefit of introducing a preconditioning step prior to running square wave voltammetry on the electrochemical fingerprint enrichment was explored. Mixtures of heroin with other drugs (cocaine, 3,4-methylenedioxymethamphetamine, and morphine) were also tested to explore the possibility of their discrimination and simultaneous detection. The feasibility of the proposed electrochemical strategies was tested on realistic heroin street samples from forensic cases, showing promising results for fast, on-site detection tools of drugs of abuse.

Electrochemical Biosensors as Potential Diagnostic Devices for Autoimmune Diseases.

An important class of biosensors is immunosensors, affinity biosensors that are based on the specific interaction between antibodies and antigens. They are classified in four classes based on the type of employed transducer: electrochemical, optical, microgravimetric, and thermometric and depending on the type of recognition elements, antibodies, aptamers, microRNAs and recently peptides are integrating parts. Those analytical devices are able to detect peptides, antibodies and proteins in various sample matrices, without many steps of sample pretreatment. Their high sensitivity, low cost and the easy integration in point of care devices assuring portability are attracting features that justify the increasing interest in their development. The use of nanomaterials, simultaneous multianalyte detection and integration on platforms to form point-of-care devices are promising tools that can be used in clinical analysis for early diagnosis and therapy monitoring in several pathologies. Taking into account the growing incidence of autoimmune disease and the importance of early diagnosis, electrochemical biosensors could represent a viable alternative to currently used diagnosis methods. Some relevant examples of electrochemical assays for autoimmune disease diagnosis developed in the last several years based on antigens, antibodies and peptides as receptors were gathered and will be discussed further.

Carcinoembryonic antigen levels correlated with advanced disease in medullary thyroid cancer.

BACKGROUND: Medullary thyroid cancer (MTC) cells are capable of secreting various tumor markers including calcitonin and carcinoembyronic antigen (CEA). The purpose of this study is to determine whether abnormal CEA levels may be used as a tumor marker to predict the severity of disease in MTC. METHODS: A retrospective analysis was completed for 33 patients with MTC who had preoperative serum CEA levels. Univariate and multivariate analyses were used to quantify the relationship between serum CEA levels and tumor stage and prognosis. RESULTS: On multivariate analysis, elevated preoperative CEA levels were significantly associated with the size and stage of tumor, distant metastasis, decreased biochemical cure, and mortality. There was a significant association between tumor size greater than 37 mm and elevated CEA levels (> 271 ng/ml). There was also a positive correlation with increased cancer stage (> 377 ng/ml), distant metastasis (> 405 ng/ml), and contralateral compartment location of lymph node metastasis (> 162 ng/ml). When pre-operative CEA levels are > 500 ng/ml, patient mortality was 67%. CONCLUSION: In this study, both pre-operative calcitonin and CEA levels were significantly correlated with the extent of disease in MTC. While calcitonin has a linear relationship with disease progression, abnormal CEA levels were a better indicator of advanced disease. CEA levels > 271 ng/ml are significant for advanced tumor size and staging, metastasis to the central compartment, and decreased chance of biochemical cure. CEA levels greater than 500 ng/ml are associated with significant patient mortality.

Tackling Poor Specificity of Cocaine Color Tests by Electrochemical Strategies.

This paper presents electrochemical strategies for the fast screening of cocaine and most common cutting agents found in seized drug samples. First, a study on the performance of Scott color tests on cocaine and a wide range of cutting agents is described. The cutting agents causing false positive or false negative results when in mixture with cocaine are identified. To overcome the lack of specificity of color tests, we further propose a fast screening strategy by means of square wave voltammetry on disposable graphite screen printed electrodes, which reveals the unique fingerprint of cocaine and cutting agents. By employing a forward and backward scan and by a dual pH strategy, we enrich the electrochemical fingerprint and enable the simultaneous detection of cocaine and cutting agents. The effectiveness of the developed strategies was tested for the detection of cocaine in seized cocaine samples and compared with the color tests. Moreover, we prove the usefulness of square wave voltammetry for predicting possible interfering agents in color tests, based on the reduction peak of cobalt thiocyanate. The developed electrochemical strategies allow for a quick screening of seized cocaine samples resulting in a selective identification of drugs and cutting agents.

Polymer platforms for selective detection of cocaine in street samples adulterated with levamisole.

Accurate drug detection is of utmost importance for fighting against drug abuse. With a high number of cutting agents and adulterants being added to cut or mask drugs in street powders the number of false results is increasing. We demonstrate for the first time the usefulness of employing polymers readily synthesized by electrodeposition to selectively detect cocaine in the presence of the commonly used adulterant levamisole. The polymers were selected by computational modelling to exhibit high binding affinity towards cocaine and deposited directly on the surface of graphene-modified electrodes via electropolymerization. The resulting platforms allowed a distinct electrochemical signal for cocaine, which is otherwise suppressed by levamisole. Square wave voltammetry was used to quantify cocaine alone and in the presence of levamisole. The usefulness of the platforms was demonstrated in the screening of real street samples.

Levamisole: a Common Adulterant in Cocaine Street Samples Hindering Electrochemical Detection of Cocaine.

The present work investigates the electrochemical determination of cocaine in the presence of levamisole, one of the most common adulterants found in cocaine street samples. Levamisole misleads cocaine color tests, giving a blue color (positive test) even in the absence of cocaine. Moreover, the electrochemical detection of cocaine is also affected by the presence of levamisole, with a suppression of the oxidation signal of cocaine. When levamisole is present in the sample in ratios higher than 1:1, the cocaine signal is no longer detected, thus leading to false negative results. Mass spectrometry and nuclear magnetic resonance were used to investigate if the signal suppression is due to the formation of a complex between cocaine and levamisole in bulk solution. Strategies to eliminate this suppressing effect are further suggested in this manuscript. In a first approach, the increase of the pH of the sample solution from pH 7 to pH 12 allowed the voltammetric determination of cocaine in the presence of levamisole in a concentration range from 10 to 5000 µM at nonmodified graphite disposable electrodes with a detection limit of 5 µM. In a second approach, the graphite electrode was cathodically pretreated, resulting in the presence of oxidation peaks of both cocaine and levamisole, with a detection limit for cocaine of 3 µM over the linear range of concentrations from 10 to 2500 µM. Both these strategies have been successfully applied for the simultaneous detection of cocaine and levamisole in three street samples on unmodified graphite disposable electrodes.

Biosensors for Alzheimer's disease biomarker detection: A review.

Alzheimer's disease (AD) is a chronic disease amongst people aged 65 and older. Increasing evidence has illustrated that early diagnosis holds the key to effective treatment of AD. A variety of detection techniques have been developed. Biosensors are excellent analytical tools which have applications in detecting the biomarkers of AD. This review includes appropriate bioreceptors to achieve highly sensitive and selective quantification of AD biomarkers by using transducers. AD biomarkers such as tau protein, amyloid ß peptides and apolipoprotein E4, are firstly summarized. The most commonly used bioreceptors, including aptamers and antibodies, are also reviewed. We introduce aptamers specific to AD biomarkers, list the sequences of aptamers designed to capture AD biomarkers and compare the properties of aptamers with those of antibodies with regard to their efficiency as bio-recognition elements. We discuss the recent progress of aptamer systems' applications in AD biomarkers in biosensing. The review also discusses novel strategies used for signal amplification in sensing AD biomarkers.

The T4/T3 quotient as a risk factor for differentiated thyroid cancer: a case control study.

BACKGROUND: The incidence of thyroid nodules is increasing among patients in North America. Few of these nodules harbour malignancy, thus further research is required to identify predictive markers of malignant thyroid disease. This study set out to understand the relationship between the levels of fT4 and fT3 and differentiated thyroid cancer. METHODS: A case-control study was conducted with 142 cases and 86 controls from the McGill University Teaching Hospitals. All patients underwent thyroid surgery. Cases were defined as patients with malignant nodules confirmed on final pathology and controls were defined as patients with benign nodules. The serological levels of TSH, fT4 and fT3 were measured preoperatively. Odds ratios were determined for each parameter and logistic regressions were calculated between markers and probability of malignancy. Additionally, fT4 values were divided by fT3 values (fT4/fT3 quotient) for each patient and an odds ratio was calculated. RESULTS: Amongst cases, the mean TSH was 2.25 ± 0.360U/mL, fT4 was 14.8 ± 0.689pmol/L, and fT3 was 4.65 ± 0.463pmol/L. Amongst controls, the mean TSH was 2.36 ± 1.68U/mL, fT4 was 14.3 ± 1.71pmol/L, and fT3 was 5.27 ± 0.957pmol/L. Patients in the control group were more likely to have low TSH, while patients in the case group would have high fT4 and patients in the control group were more likely to have a low fT4. The OR for patients with TSH >4.4U/mL was 2.13 (0.97, 4.65), and for patients with TSH <0.4U/mL was 0.46 (0.22, 0.95). The OR for patients with fT4 > 16pmol/L was 2.10 (1.09, 4.06), and for patients with fT4 < 10pmol/L was 0.45 (0.20, 0.98). The OR for patients with fT3 > 5.5pmol/L was 0.39 (0.14, 1.28). The OR for patients with fT3 < 3pmol/L was 1.83 (0.25, 13.69). The average fT4/fT3 was 3.39 ± 0.206 for cases and 2.93 ± 0.467 for controls. The fT4/fT3 quotient was considered high if it was >3.3 (OR =6.00 (2.94, 12.25)). CONCLUSION: In this study, a direct relationship between high levels of fT4 and malignancy was uncovered. Furthermore, low levels of TSH and fT4 increased the likelihood that a nodule was benign. In this study a fT4/fT3 ratio >3.3 increased the risk of malignancy by 3.6 times (p-value =0.0013).