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A letter to the editor is presented commenting on the article "Population differences in finger-length ratios: Ethnicity or latitude?" by J.C. Loehlin and colleagues, featured in a 2006 issue of the "Archives of Sexual Behavior."

Optoacoustic imaging has grown in clinical relevance due to inherent advantages in sensitivity, resolution, and imaging depth, but the development of contrast agents is lacking. This study assesses the influence of structural features of squaraine dyes on optoacoustic activity through computational models, in vitro testing, and in vivo experimentation. The squaraine scaffold was decorated with halogens and side-chain extensions. Extension of side chains and heavy halogenation of squaraines both increased optoacoustic signals individually, although they had a more significant effect in tandem. Density functional theory models suggest that the origin of the increased optoacoustic signal is the increase in transition dipole moment and vibrational entropy, which manifested as increased absorbance in near-infrared region (NIR) wavelengths and decreased fluorescence quantum yield. This study provides insight into the structure-function relationships that will lead guiding principles for optimizing optoacoustic contrast agents. Further developments of squaraines and other agents will further increase the relevance of optoacoustic imaging in a clinical setting., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.

A novel electrochemical platform for amaranth determination has been developed using a rapid, easy, inexpensive, and portable molecularly imprinted polymer technique. The MIP platform was fabricated by electropolymerizing melamine as monomer in the presence of amaranth as template on the surface of ZnO-MWCNT/SPCE. Then, amaranth was completely eluted, leaving imprinted cavities in the polymeric film that could effectively recognize amaranth in solution. The electrochemical platform based on a molecularly imprinted polymelamine was analyzed by scanning electron microscopy (SEM), cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and differential pulse voltammetry (DPV). Under optimum conditions, the developed MIP/ZnO-MWCNT/SPCE platform can be properly used for amaranth determination, with high sensitivity of 96.2 µA µM cm -2 , two linear concentration ranges (0.01 to 1 µM and 1 to 1000 µM) and a low limit of detection of 0.003 µM. The anodic peak potential of amaranth was found to be 0.73 V. Additionally, the polymelamine MIP films specifically recognize amaranth molecules, making it possible to detect amaranth in a complex solution with high selectivity, excellent repeatability, reproducibility, and stability. The MIP/ZnO-MWCNT modified screen-printed carbon electrode was successfully applied to determine amaranth in pharmaceutical and water samples, with recovery values ranging from 99.7 to 102% and RSD% values less than 3.2%., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

A multimode sensor (a sensor responding simultaneously to more than one mode, e.g., stochastic mode, amperometric mode, voltammetric mode) based on graphite paste modified with N -methylfulleropyrrolidine was proposed for the determination of butoconazole nitrate in its pharmaceutical formulation. The stochastic mode and square wave voltammetry mode were applied for the determinations. Both the stochastic mode and square wave voltammetry mode were applied for a qualitative and quantitative assay of butoconazole nitrate. The sensor can be used between 1.68 × 10 -6 and 1.68 × 10 4 μmol L -1 when the stochastic mode is used and between 0.168 and 16.80 μmol L -1 when the square wave voltammetry mode is used. The multimode sensor was reliably used for the determination of butoconazole nitrate in its pharmaceutical formulation, Gynofort cream, the recorded recoveries being higher than 99.00%, with RSD (%) values of lower than 2.00%., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Monoacylglycerol lipase (MAGL) constitutes a serine hydrolase that orchestrates endocannabinoid homeostasis and exerts its function by catalyzing the degradation of 2-arachidonoylglycerol (2-AG) to arachidonic acid (AA). As such, selective inhibition of MAGL represents a potential therapeutic and diagnostic approach to various pathologies including neurodegenerative disorders, metabolic diseases and cancers. Based on a unique 4-piperidinyl azetidine diamide scaffold, we developed a reversible and peripheral-specific radiofluorinated MAGL PET ligand [ 18 F]FEPAD. Pharmacokinetics and binding studies on [ 18 F]FEPAD revealed its outstanding specificity and selectivity towards MAGL in brown adipose tissue (BAT) - a tissue that is known to be metabolically active. We employed [ 18 F]FEPAD in PET studies to assess the abundancy of MAGL in BAT deposits of mice and found a remarkable degree of specific tracer binding in the BAT, which was confirmed by post-mortem tissue analysis. Given the negative regulation of endocannabinoids on the metabolic BAT activity, our study supports the concept that dysregulation of MAGL is likely linked to metabolic disorders. Further, we now provide a suitable imaging tool that allows non-invasive assessment of MAGL in BAT deposits, thereby paving the way for detailed mechanistic studies on the role of BAT in endocannabinoid system (ECS)-related pathologies., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Alterations in brain cholesterol homeostasis have been broadly implicated in neurological disorders. Notwithstanding the complexity by which cholesterol biology is governed in the mammalian brain, excess neuronal cholesterol is primarily eliminated by metabolic clearance via cytochrome P450 46A1 (CYP46A1). No methods are currently available for visualizing cholesterol metabolism in the living human brain; therefore, a noninvasive technology that quantitatively measures the extent of brain cholesterol metabolism via CYP46A1 could broadly affect disease diagnosis and treatment options using targeted therapies. Here, we describe the development and testing of a CYP46A1-targeted positron emission tomography (PET) tracer, 18 F-CHL-2205 ( 18 F-Cholestify). Our data show that PET imaging readouts correlate with CYP46A1 protein expression and with the extent to which cholesterol is metabolized in the brain, as assessed by cross-species postmortem analyses of specimens from rodents, nonhuman primates, and humans. Proof of concept of in vivo efficacy is provided in the well-established 3xTg-AD murine model of Alzheimer's disease (AD), where we show that the probe is sensitive to differences in brain cholesterol metabolism between 3xTg-AD mice and control animals. Furthermore, our clinical observations point toward a considerably higher baseline brain cholesterol clearance via CYP46A1 in women, as compared to age-matched men. These findings illustrate the vast potential of assessing brain cholesterol metabolism using PET and establish PET as a sensitive tool for noninvasive assessment of brain cholesterol homeostasis in the clinic.

Objectives: To enable non-invasive real-time quantification of vasopressin 1A (V1A) receptors in peripheral organs, we sought to develop a suitable PET probe that would allow specific and selective V1A receptor imaging in vitro and in vivo., Methods: We synthesized a high-affinity and -selectivity ligand, designated compound 17. The target structure was labeled with carbon-11 and tested for its utility as a V1A-targeted PET tracer by cell uptake studies, autoradiography, in vivo PET imaging and ex vivo biodistribution experiments., Results: Compound 17 (PF-184563) and the respective precursor for radiolabeling were synthesized in an overall yield of 49% (over 7 steps) and 40% (over 8 steps), respectively. An inhibitory constant of 0.9 nM towards the V1A receptors was measured, while excellent selectivity over the related V1B, V2 and OT receptor (IC 50 >10,000 nM) were obtained. Cell uptake studies revealed considerable V1A binding, which was significantly reduced in the presence of V1A antagonists. Conversely, there was no significant blockade in the presence of V1B and V2 antagonists. In vitro autoradiography and PET imaging studies in rodents indicated specific tracer binding mainly in the liver. Further, the pancreas, spleen and the heart exhibited specific binding of [ 11 C]17 ([ 11 C]PF-184563) by ex vivo biodistribution experiments., Conclusion: We have developed the first V1A-targeted PET ligand that is suitable for subtype-selective receptor imaging in peripheral organs including the liver, heart, pancreas and spleen. Our findings suggest that [ 11 C]PF-184563 can be a valuable tool to study the role of V1A receptors in liver diseases, as well as in cardiovascular pathologies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Monoacylglycerol lipase (MAGL) is a 33 kDa serine protease primarily responsible for hydrolyzing 2-arachidonoylglycerol into the proinflammatory eicosanoid precursor arachidonic acid in the central nervous system. Inhibition of MAGL constitutes an attractive therapeutic concept for treating psychiatric disorders and neurodegenerative diseases. Herein, we present the design and synthesis of multiple reversible MAGL inhibitor candidates based on a piperazinyl azetidine scaffold. Compounds 10 and 15 were identified as the best-performing reversible MAGL inhibitors by pharmacological evaluations, thus channeling their radiolabeling with fluorine-18 in high radiochemical yields and favorable molar activity. Furthermore, evaluation of [ 18 F] 10 and [ 18 F] 15 ([ 18 F]MAGL-2102) by autoradiography and positron emission tomography (PET) imaging in rodents and nonhuman primates demonstrated favorable brain uptakes, heterogeneous radioactivity distribution, good specific binding, and adequate brain kinetics, and [ 18 F] 15 demonstrated a better performance. In conclusion, [ 18 F] 15 was found to be a suitable PET radioligand for the visualization of MAGL, harboring potential for the successful translation into humans.

As a serine hydrolase, monoacylglycerol lipase (MAGL) is principally responsible for the metabolism of 2-arachidonoylglycerol (2-AG) in the central nervous system (CNS), leading to the formation of arachidonic acid (AA). Dysfunction of MAGL has been associated with multiple CNS disorders and symptoms, including neuroinflammation, cognitive impairment, epileptogenesis, nociception and neurodegenerative diseases. Inhibition of MAGL provides a promising therapeutic direction for the treatment of these conditions, and a MAGL positron emission tomography (PET) probe would greatly facilitate preclinical and clinical development of MAGL inhibitors. Herein, we design and synthesize a small library of fluoropyridyl-containing MAGL inhibitor candidates. Pharmacological evaluation of these candidates by activity-based protein profiling identified 14 as a lead compound, which was then radiolabeled with fluorine-18 via a facile S N Ar reaction to form 2-[ 18 F]fluoropyridine scaffold. Good blood-brain barrier permeability and high in vivo specific binding was demonstrated for radioligand [ 18 F] 14 (also named as [ 18 F]MAGL-1902). This work may serve as a roadmap for clinical translation and further design of potent 18 F-labeled MAGL PET tracers., Competing Interests: The authors have no conflicts of interest to declare., (© 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Introduction: According to WHO, in worldwide cancer mortality statistics, the first place is occupied by bronchopulmonary cancer. This reason has led us to carry out the present pilot study, was with the participation of the Clinics of Carol Davila University of Medicine and Pharmacy Bucharest in order to apply a technique developed earlier by Stefan-van Staden, for early detection of this type of cancer, initiate a personalized diagnosis, and implicitly apply a personalized treatment in order to increase the life expectancy among these patients. In recent years, there has been a tendency to find fast non-invasive screening methods for the early diagnosis of cancer. Therefore, the present pilot study proposed simultaneous detection of tumor markers (NSE and CEA) by different methods: (1) ELISA kits, (2) the method developed earlier by Stefan-van Staden-which used stochastic sensors, and (3) IHC. All selected patients selected by Dr Claudiu-Eduard Nistor, were suspected of microcellular bronchopulmonary cancer. Tumor tissue samples were collected by conventional and minimally invasive surgical techniques. The results obtained for the detection of markers in blood using ELISA, and stochastic methods (based on stochastic sensors) were correlated with the results obtained using anatomopathological and immunohistochemical analysis of the tumor tissues., Experimental: Stochastic sensors have been used to analyze NSE in blood samples and whole tissues. The IHC was performed for analyzing tumor tissue using standard procedures. ELISA has been used as a standard method to determine specific biomarkers in whole blood samples., Results and Discussion: A good correlation was found for results obtained using stochastic and ELISA methods, and IHC for blood and tissue analysis. Statistical evaluation of the data showed that the results of whole blood analysis are correlating very good with the analysis of pulmonary tumor tissue. Therefore, the stochastic method can be used for the detection and for the pursuit of therapeutic efficiency., Conclusions: The data obtained, as well as the statistics, showed that the proposed method can be used as a screening method for fast and early detection of microcellular bronchopulmonary, being minim invasive. It can also be used for monitoring the therapeutic efficiency of the prescribed medication.

Dysfunction of monoacylglycerol lipase (MAGL) is associated with several psychopathological disorders, including drug addiction and neurodegenerative diseases. Herein we design, synthesize, and evaluate several irreversible fluorine-containing MAGL inhibitors for positron emission tomography (PET) ligand development. Compound 6 (identified from a therapeutic agent) was advanced for 18 F-labeling via a novel spirocyclic iodonium ylide (SCIDY) strategy, which demonstrated high brain permeability and excellent specific binding. This work supports further development of novel 18 F-labeled MAGL PET probes.

Testosterone is the principal endogenous androgenic-anabolic steroid in humans. The levels of testosterone in the human body are correlated with many hormonal disorders (hypogonadism, impotence, etc) mostly in men, and with many types of diseases such as: prostate cancer, metabolic syndrome, obesity, cardiovascular diseases and so on. Testosterone is extensively used among sportsmen willing to increase strength, aggressiveness, and recovery; making it the most commonly reported substance in steroid abuse. Fast, easy and cheap methods for the evaluation of testosterone are extremely needed in clinics and hospitals. This review is dedicated to surveying recent determination methods of testosterone from different biological samples such as: serum, saliva, plasma, urine or fingernail samples. After a brief description of the role of this steroid hormone in the biomedical field, various types of determination methods are described. The most important methods are immunoassays, liquid chromatography tandem massspectrometry and electrochemical methods. Different types of sensors were designed for the rapid assessment of testosterone: immunosensors, biosensors, stochastic or multimode sensors. One can conclude that to date, the available methods of analysis can cover a wide concentration range, able to detect testosterone from children`s saliva, where the levels are the lowest (using stochastic sensors), to whole blood, where electrochemical, immunological and chromatographic methods can be used., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Following the recognition of a measles case in a hospital in The Netherlands, health care workers (HCW) from the premises were screened by a commercial enzyme immunoassay (EIA) for measles IgG to identify persons at risk for measles. At least 10% of the HCW were tested measles IgG-negative. As this was considered an unusually high proportion, we hypothesized suboptimal sensitivity of EIAs, especially in medical personnel that had vaccine-induced immunity rather than antibodies resulting from natural infection., Objectives: To determine (vaccine-induced) measles immunity in HCW, using different EIAs compared to the plaque reduction neutralization (PRN) test, the best surrogate marker for vaccine efficacy and immune protection., Study Design: Sera from HCW were tested for measles IgG antibodies in three commercial EIAs, in a bead-based multiplex immunoassay (MIA) and in the PRN test, and evaluated against age and vaccination history of the HCW., Results: Of the 154 HCW, born between 1960 and 1995, 153 (99.4%) had protective levels of measles antibodies (PRN> 120mIU/ml). The three EIAs failed to detect any measles IgG antibodies in approximately 10% of the HCW, while this percentage was approximately 3% for the MIA. Negative IgG results rose to 19% for individuals born between 1975 and 1985, pointing to an age group largely representing vaccinated persons from the first measles vaccination period in The Netherlands., Conclusion: The results show limitations in the usefulness of current EIA assays for determining protective measles antibodies in persons with a vaccination history., (Copyright © 2015 Elsevier B.V. All rights reserved.)