Vibrational spectroscopy: a promising approach to discriminate neurodegenerative disorders

Neurodegenerative diseases are a growing burden in modern society, thus crucially calling for the development of accurate diagnostic strategies. These diseases are currently incurable, a fact which has been attributed to their late diagnosis, after brain damage has already become widespread. An earlier and improved diagnosis is necessary for the enrolment of patients into clinical trials and can pave the way for the development of therapeutic tactics. Novel analytical techniques, such as mass spectrometry and vibrational spectroscopy, have been able to successfully detect and characterise neurodegenerative disorders. It is critical to globally support and make use of innovative basic research and techniques, which could ultimately lead to the creation of a cost-effective diagnostic test. Minimally invasive samples, such as biological fluids, have also been shown to reveal information for these diseases; utilising them could simplify sample collection/analysis and be more preferable to patients

Infrared Spectroscopy Coupled with a Dispersion Model for Quantifying the Real-Time Dynamics of Kanamycin Resistance in Artificial Microbiota

Overusage of antibiotics leads to the widespread induction of antibiotic-resistance genes (ARGs). Developing an approach to allow real-time monitoring and fast prediction of ARGs dynamics in clinical or environmental samples has become an urgent matter. Vibrational spectroscopy is potentially an ideal technique toward the characterization of the microbial composition of microbiota as it is nondestructive, high-throughput, and label-free. Herein, we employed attenuated total reflection Fourier transform infrared (ATR-FT-IR) spectroscopy and developed a spectrochemical tool to quantify the static and dynamic composition of kanamycin resistance in artificial microbiota to evaluate microbial antibiotic resistance. Second-order differentiation was introduced in identifying the spectral biomarkers, and principal component analysis followed by linear discriminant analysis (PCA-LDA) was used for the multivariate analysis of the entire spectral features employed. The calculated results of the mathematical dispersion model coupled with PCA-LDA showed high similarity to the designed microbiota structure, with no significant difference (P > 0.05) in the static treatments. Moreover, our model successfully predicted the dynamics of kanamycin resistance within artificial microbiota under kanamycin pressures. This work lends new insights into the potential role of spectrochemical analyses in investigating the existence and trends of antibiotic resistance in microbiota

Underlying role of mitochondrial mutagenesis in the pathogenesis of a disease and current approaches for translational research

Mitochondrial diseases have been extensively investigated over the last three decades but many questions regarding their underlying aetiologies remain unanswered. Mitochondrial dysfunction is not only responsible for a range of neurological and myopathy diseases, but is also considered pivotal in a broader spectrum of common diseases such as epilepsy, autism and bipolar disorder. These disorders are a challenge to diagnose and treat as their aetiology might be multifactorial. In this review, the focus is placed on potential mechanisms capable of introducing defects in mitochondria resulting in disease. Special attention is given to the influence of xenobiotics on mitochondria; environmental factors inducing mutations or epigenetic changes in the mitochondrial genome can alter its expression and impair the whole cell’s functionality. Specifically, we suggest that environmental agents can cause damage by generating abasic sites in mitochondrial DNA, which consequently lead to mutagenesis. Abasic sites are observed in DNA after spontaneous loss of a nucleic base (e.g., “apurinic sites” after loss of purines, adenine or guanine) or through base excision repair; if left unrepaired, they can produce mutagenic DNA lesions. Moreover, we describe current approaches for handling mitochondrial diseases, as well as available prenatal diagnostic tests towards eliminating these maternally-inherited diseases. Undoubtedly, more research is required, as current therapeutic approaches mostly employ palliative therapies rather than targeting primary mechanisms or prophylactic approaches. More effort is needed into further unravelling the relationship between xenobiotics and mitochondria as the extent of influence in mitochondrial pathogenesis is increasingly recognised

Differential diagnosis of Alzheimer’s disease using spectrochemical analysis of blood

The progressive aging of the world’s population makes a higher prevalence of neurodegenerative diseases inevitable. The necessity for an accurate, but at the same time, inexpensive and minimally invasive, diagnostic test is urgently required, not only to confirm the presence of the disease but also to discriminate between different types of dementia to provide the appropriate management and treatment. In this study, attenuated total reflection FTIR (ATR-FTIR) spectroscopy combined with chemometric techniques were used to analyze blood plasma samples from our cohort. Blood samples are easily collected by conventional venepuncture, permitting repeated measurements from the same individuals to monitor their progression throughout the years or evaluate any tested drugs. We included 549 individuals: 347 with various neurodegenerative diseases and 202 age-matched healthy individuals. Alzheimer’s disease (AD; n = 164) was identified with 70% sensitivity and specificity, which after the incorporation of apolipoprotein ε4 genotype (APOE ε4) information, increased to 86% when individuals carried one or two alleles of ε4, and to 72% sensitivity and 77% specificity when individuals did not carry ε4 alleles. Early AD cases (n = 14) were identified with 80% sensitivity and 74% specificity. Segregation of AD from dementia with Lewy bodies (DLB; n = 34) was achieved with 90% sensitivity and specificity. Other neurodegenerative diseases, such as frontotemporal dementia (FTD; n = 30), Parkinson’s disease (PD; n = 32), and progressive supranuclear palsy (PSP; n = 31), were included in our cohort for diagnostic purposes. Our method allows for both rapid and robust diagnosis of neurodegeneration and segregation between different dementias

Diagnostic Biomarkers for Alzheimer's Disease Using Non-Invasive Specimens

Studies in the field of Alzheimer's disease (AD) have shown the emergence of biomarkers in biologic fluids that hold great promise for the diagnosis of the disease. A diagnosis of AD at a presymptomatic or early stage may be the key for a successful treatment, with clinical trials currently investigating this. It is anticipated that preventative and therapeutic strategies may be stage-dependent, which means that they have a better chance of success at a very early stage-before critical neurons are lost. Several studies have been investigating the use of cerebrospinal fluid (CSF) and blood as clinical samples for the detection of AD with a number of established core markers, such as amyloid beta (Aβ), total tau (T-tau) and phosphorylated tau ( tau), being at the center of clinical research interest. The use of oral samples-including saliva and buccal mucosal cells-falls under one of the least-investigated areas in AD diagnosis. Such samples have great potential to provide a completely non-invasive alternative to current CSF and blood sampling procedures. The present work is a thorough review of the results and analytical approaches, including proteomics, metabolomics, spectroscopy and microbiome analyses that have been used for the study and detection of AD using salivary samples and buccal cells. With a few exceptions, most of the studies utilizing oral samples were performed in small cohorts, which in combination with the existence of contradictory results render it difficult to come to a definitive conclusion on the value of oral markers. Proteins such as Aβ, T-tau and tau, as well as small metabolites, were detected in saliva and have shown some potential as future AD diagnostics. Future large-cohort studies and standardization of sample preparation and (pre-)analytical factors are necessary to determine the use of these non-invasive samples as a diagnostic tool for AD

Aluminium foil as an alternative substrate for the spectroscopic interrogation of endometrial cancer

Biospectroscopy has the potential to investigate and characterise biological samples and could, therefore, be utilised to diagnose various diseases in a clinical environment. An important consideration in spectrochemical studies is the cost-effectiveness of the substrate used to support the sample, as high expense would limit their translation into clinic. In this paper, the performance of low-cost aluminium (Al) foil substrates was compared with the commonly used low-emissivity (low-E) slides. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy was used to analyse blood plasma and serum samples from women with endometrial cancer and healthy controls. The two populations were differentiated using principal component analysis with support vector machines (PCA-SVM) with 100% sensitivity in plasma samples (endometrial cancer=70; healthy controls=15) using both Al foil and low-E slides as substrates. The same sensitivity results (100%) were achieved for serum samples (endometrial cancer=60; healthy controls=15). Specificity was found higher using Al foil (90%) in comparison to low-E slides (85%) and lower using Al foil (70%) in comparison to low-E slides in serum samples. The establishment of Al foil as low-cost and highly-performing substrate would pave the way for large-scale, multi-centre studies and potentially for routine clinical use

Female dynamics in authorship of scientific publications in the Public Library of Science: a 10-year bibliometric analysis of biomedical research

Women are generally underrepresented in science, technology, engineering, and mathematics (STEM). As scientific production reflects scholarly impact and participation in the scientific process, the number of journal publications forms a pertinent measure of academic productivity. This study examined the prevalence and evolution of female representation in prominent author positions across multidisciplinary biomedical research. Publications from seven exemplar cross-specialty journals of the Public Library of Science (PLoS Medicine, PLoS Biology, PLoS One, PLoS Computational Biology, PLoS Genetics, PLoS Pathogens, and PLoS Neglected Tropical Diseases) between January 2010 and December 2020 were extracted from Web of Science. Using Genderize.io, the gender of authors from their first names was estimated using a 75% threshold. The association between female prevalence in first and last authorship and journal was evaluated using a binary logistic regression, and odds ratios were estimated against a 50:50 reference on gender. In 266,739 publications, 43.3% of first authors and 26.7% of last authors were females. Across the ten-year period, female first authorship increased by 19.6% and last authorship by 3.2%. Among all journals, PLoS Neglected Tropical Diseases had the greatest total proportion of female first authors (45.7%) and PLoS Medicine of female last authors (32%), while PLoS Computational Biology had the lowest proportion in these categories (23.7% and 17.2%). First authors were less likely to be females in all PLoS journals (p < 0.05) except for PLoS Neglected Tropical Diseases (odds ratio: 0.84, 95% confidence interval: 0.71–1.00), where the odds of female authorship were not significantly different (p = 0.054). Last authors were not more likely to be females in all PLoS journals (p < 0.001). Overall, women still appear underrepresented as first authors in biomedical publications and their representation as last authors has severely lagged. Efforts towards gender equality in scholarly authorship will contribute to the representation of women in biomedical research and ensure that their potential is not lost

Obstetric outcomes after conservative treatment for cervical intraepithelial lesions and early invasive disease.

BACKGROUND: The mean age of women undergoing local treatment for pre-invasive cervical disease (cervical intra-epithelial neoplasia; CIN) or early cervical cancer (stage IA1) is around their 30s and similar to the age of women having their first child. Local cervical treatment has been correlated to adverse reproductive morbidity in a subsequent pregnancy, however, published studies and meta-analyses have reached contradictory conclusions. OBJECTIVES: To assess the effect of local cervical treatment for CIN and early cervical cancer on obstetric outcomes (after 24 weeks of gestation) and to correlate these to the cone depth and comparison group used. SEARCH METHODS: We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library, 2017, Issue 5), MEDLINE (up to June week 4, 2017) and Embase (up to week 26, 2017). In an attempt to identify articles missed by the search or unpublished data, we contacted experts in the field and we handsearched the references of the retrieved articles and conference proceedings. SELECTION CRITERIA: We included all studies reporting on obstetric outcomes (more than 24 weeks of gestation) in women with or without a previous local cervical treatment for any grade of CIN or early cervical cancer (stage IA1). Treatment included both excisional and ablative methods. We excluded studies that had no untreated reference population, reported outcomes in women who had undergone treatment during pregnancy or had a high-risk treated or comparison group, or both DATA COLLECTION AND ANALYSIS: We classified studies according to the type of treatment and the obstetric endpoint. Studies were classified according to method and obstetric endpoint. Pooled risk ratios (RR) and 95% confidence intervals (CIs) were calculated using a random-effects model and inverse variance. Inter-study heterogeneity was assessed with I2 statistics. We assessed maternal outcomes that included preterm birth (PTB) (spontaneous and threatened), preterm premature rupture of the membranes (pPROM), chorioamnionitis, mode of delivery, length of labour, induction of delivery, oxytocin use, haemorrhage, analgesia, cervical cerclage and cervical stenosis. The neonatal outcomes included low birth weight (LBW), neonatal intensive care unit (NICU) admission, stillbirth, perinatal mortality and Apgar scores. MAIN RESULTS: We included 69 studies (6,357,823 pregnancies: 65,098 pregnancies of treated and 6,292,725 pregnancies of untreated women). Many of the studies included only small numbers of women, were of heterogenous design and in their majority retrospective and therefore at high risk of bias. Many outcomes were assessed to be of low or very low quality (GRADE assessment) and therefore results should be interpreted with caution. Women who had treatment were at increased overall risk of preterm birth (PTB) (less than 37 weeks) (10.7% versus 5.4%, RR 1.75, 95% CI 1.57 to 1.96, 59 studies, 5,242,917 participants, very low quality), severe (less than 32 to 34 weeks) (3.5% versus 1.4%, RR 2.25, 95% CI 1.79 to 2.82), 24 studies, 3,793,874 participants, very low quality), and extreme prematurity (less than 28 to 30 weeks) (1.0% versus 0.3%, (RR 2.23, 95% CI 1.55 to 3.22, 8 studies, 3,910,629 participants, very low quality), as compared to women who had no treatment.The risk of overall prematurity was higher for excisional (excision versus no treatment: 11.2% versus 5.5%, RR 1.87, 95% CI 1.64 to 2.12, 53 studies, 4,599,416 participants) than ablative (ablation versus no treatment: 7.7% versus 4.6%, RR 1.35, 95% CI 1.20 to 1.52, 14 studies, 602,370 participants) treatments and the effect was higher for more radical excisional techniques (less than 37 weeks: cold knife conisation (CKC) (RR 2.70, 95% CI 2.14 to 3.40, 12 studies, 39,102 participants), laser conisation (LC) (RR 2.11, 95% CI 1.26 to 3.54, 9 studies, 1509 participants), large loop excision of the transformation zone (LLETZ) (RR 1.58, 95% CI 1.37 to 1.81, 25 studies, 1,445,104 participants). Repeat treatment multiplied the risk of overall prematurity (repeat versus no treatment: 13.2% versus 4.1%, RR 3.78, 95% CI 2.65 to 5.39, 11 studies, 1,317,284 participants, very low quality). The risk of overall prematurity increased with increasing cone depth (less than 10 mm to 12 mm versus no treatment: 7.1% versus 3.4%, RR 1.54, 95% CI 1.09 to 2.18, 8 studies, 550,929 participants, very low quality; more than 10 mm to 12 mm versus no treatment: 9.8% versus 3.4%, RR 1.93, 95% CI 1.62 to 2.31, 8 studies, 552,711 participants, low quality; more than 15 mm to 17 mm versus no treatment: 10.1 versus 3.4%, RR 2.77, 95% CI 1.95 to 3.93, 4 studies, 544,986 participants, very low quality; 20 mm or more versus no treatment: 10.2% versus 3.4%, RR 4.91, 95% CI 2.06 to 11.68, 3 studies, 543,750 participants, very low quality). The comparison group affected the magnitude of effect that was higher for external, followed by internal comparators and ultimately women with disease, but no treatment. Untreated women with disease and the pre-treatment pregnancies of the women who were treated subsequently had higher risk of overall prematurity than the general population (5.9% versus 5.6%, RR 1.24, 95% CI 1.14 to 1.34, 15 studies, 4,357,998 participants, very low quality).pPROM (6.1% versus 3.4%, RR 2.36, 95% CI 1.76 to 3.17, 21 studies, 477,011 participants, very low quality), low birth weight (7.9% versus 3.7%, RR 1.81, 95% CI 1.58 to 2.07, 30 studies, 1,348,206 participants, very low quality), NICU admission rate (12.6% versus 8.9%, RR 1.45, 95% CI 1.16 to 1.81, 8 studies, 2557 participants, low quality) and perinatal mortality (0.9% versus 0.7%, RR 1.51, 95% CI 1.13 to 2.03, 23 studies, 1,659,433 participants, low quality) were also increased after treatment. AUTHORS' CONCLUSIONS: Women with CIN have a higher baseline risk for prematurity. Excisional and ablative treatment appears to further increases that risk. The frequency and severity of adverse sequelae increases with increasing cone depth and is higher for excision than it is for ablation. However, the results should be interpreted with caution as they were based on low or very low quality (GRADE assessment) observational studies, most of which were retrospective

Precise Hybrid-Actuation Robotic Fiber for Enhanced Cervical Disease Treatment

Treatment for high-grade precancerous cervical lesions and early-stage cancers, mainly affecting women of reproductive age, often involves fertility-sparing treatment methods. Commonly used local treatments for cervical precancers have shown the risk of leaving a positive cancer margin and engendering subsequent complications according to the precision and depth of excision. An intra-operative device that allows the careful excision of the disease while conserving healthy cervical tissue would potentially enhance such treatment. In this study, we developed a polymer-based robotic fiber measuring 150 mm in length and 1.7 mm in diameter, fabricated using a highly scalable fiber drawing technique. This robotic fiber utilizes a hybrid actuation mechanism, combining electrothermal and tendon-driven actuation mechanisms, thus enabling a maximum motion range of 46 mm from its origin with a sub-100 {\mu}m motion precision. We also developed control algorithms for the actuation methods of this robotic fiber, including predefined path control and telemanipulation, enabling coarse positioning of the fiber tip to the target area followed by a precise scan. The combination of a surgical laser fiber with the robotic fiber allows for high-precision surgical ablation. Additionally, we conducted experiments using a cervical phantom that demonstrated the robotic fiber's ability to access and perform high-precision scans, highlighting its potential for cervical disease treatments and improvement of oncological outcomes