Identification of thermolabile positional isomers of N-(2-hydroxybenzyl)-2-(dimethoxyphenyl)ethanamines (NBOH series) using chromatography and mass spectrometry methods.

Among N-((2-substituted)benzyl)phenylethanamines, N-(2-hydroxybenzyl)phenylethanamines are a special type of compounds which are thermolabile and degrade in the course of analysis by means of gas chromatography-mass spectrometry (GC-MS). This can lead to substantial errors, in the identification of legally controlled compounds of this series containing methoxy groups at positions 2 and 5 of the benzene ring of the phenylethyl fragment by GC-MS, which is commonly used in forensic and toxicological laboratories. Exemplified by the five isomeric 2-(dimethoxyphenyl)-N-(2-hydroxybenzyl)ethanamines, it was shown that their derivatization with trifluoroacetic anhydride (same as in the case of the N-(2-methoxybenzyl)-, N-(2-fluorobenzyl)-, N-(2-chlorobenzyl)-, and N-(2-bromobenzyl)substitutes phenylethanamines [NBOMe, NBF, NBCl, and NBBr, respectively] series described earlier) results in only one product, N-monosubstituted derivative, for each positional isomer within a series, which makes it possible to reliably identify each compound by the GC-MS method.

Differences in help-seeking tendency in intimate partner violence between Jewish and Arab women in Israel.

Objective: Intimate partner violence (IPV) has many consequences for the physical and mental health of the victims. One strategy for coping with IPV is to turn to formal and informal sources for help. The purpose of the present study was to examine the differences in help seeking tendency in cases of IPV between Jewish and Arab women in Israel and the connection to their mental health.

Spatial-temporal correlations in the speckle pattern for the characterization of cellular motion within a 3D object.

Dynamic light scattering analysis has been demonstrated recently to be a promising tool for the assessment of structural changes taking place inside opaque tissue samples. Specifically, quantification of velocity and direction of cellular motion inside spheroids and organoids has attracted much attention as a potent indicator in personalized therapy research. Here, we propose a method for the quantitative extraction of cellular motion, velocity, and direction, by applying a concept of speckle spatial-temporal correlation dynamics.

A road map for in vivo evolution experiments with blood-borne parasitic microbes.

Laboratory experiments in which blood-borne parasitic microbes evolve in their animal hosts offer an opportunity to study parasite evolution and adaptation in real time and under natural settings. The main challenge of these experiments is to establish a protocol that is both practical over multiple passages and accurately reflects natural transmission scenarios and mechanisms. We provide a guide to the steps that should be considered when designing such a protocol, and we demonstrate its use via a case study.

Severe post-gastric bypass hypoglycemia in pregnancy.

Post-bariatric surgery hypoglycemia (PBH) is a serious and relatively prevalent complication of bariatric surgery and is often underdiagnosed due to unawareness. PBH can have a profound effect on health and quality of life. Data regarding the natural history and management of PBH during pregnancy are lacking.

Selective Synthesis of Azoloyl -1,2,3-Triazoles and Azolyl Diazoketones: Experimental and Computational Insights.

Here, we report that the reaction of enaminones, from a class of azole series, with sulfonyl azides leads to a difficult-to-separate mixture of two pairs of compounds: (1) 4-azoloyl--1,2,3-triazoles with sulfonamides and (2) azolyl diazoketones with -sulfonamidines, as a result of the implementation of two competing reactions. On one hand, the electron-donating methyl or methoxy group in the aryl para-position of arylsulfonyl azides favors the production of -1,2,3-triazoles together with sulfonamides. On the other hand, the use of highly electrophilic 4-nitrophenylsulfonyl azide promotes the formation of diazoketones and sulfonamidines.

Potential of chromatography and mass spectrometry for the differentiation of three series of positional isomers of 2-(dimethoxyphenyl)-N-(2-halogenobenzyl)ethanamines.

N-(2-substituted benzyl)-2,5-dimethoxyphenethylamines often cause severe poisonings which has led to their legal prohibition in many countries. At the same time, their positional isomers can be studied as potential therapeutic drugs. In this regard, the search for various approaches to differentiate these isomers is an important practical task, the solution of which would guarantee from identification errors during laboratory analysis.

Co-culture hydrogel micro-chamber array-based plate for anti-tumor drug development at single-element resolution.

In response to the need for reliable cellular models that reflect complex tumor microenvironmental properties, and enable more precise testing of anti-cancer therapeutics effects on humans, a co-culture platform for in-vitro model that enhances the physiology of breast cancer (BC) microenvironment is presented. A six well imaging plate wherein each macro-well contains several separate compartments was designed. Three-dimensional (3D) cancer spheroids are generated and cultured in the inner compartment which is embossed with an array of nano-liter micro-chambers made of hydrogel.

Synthesis and determination of analytical characteristics and differentiation of positional isomers in the series of N-(2-methoxybenzyl)-2-(dimethoxyphenyl)ethanamine using chromatography-mass spectrometry.

N-(2-Methoxybenzyl)-2,5-dimethoxyphenethylamines (NBOMes) are synthetic phenethylamine derivatives emerging on the global drug market and reported to be associated with untoward effects in people who use drugs. Its action involves agonism at serotonin 5-HT receptors, affecting cognitive and behavioral processes. However, certain isomers of NBOMes may not show any psychoactive effects.

Analysis of Cancer Cell Invasion and Anti-metastatic Drug Screening Using Hydrogel Micro-chamber Array (HMCA)-based Plates.

Cancer metastasis is known to cause 90% of cancer lethality. Metastasis is a multistage process which initiates with the penetration/invasion of tumor cells into neighboring tissue. Thus, invasion is a crucial step in metastasis, making the invasion process research and development of anti-metastatic drugs, highly significant.

Nitric oxide is cytoprotective to breast cancer spheroids vulnerable to estrogen-induced apoptosis.

Estrogen-induced apoptosis has become a successful treatment for postmenopausal metastatic, estrogen receptor-positive breast cancer. Nitric oxide involvement in the response to this endocrine treatment and its influence upon estrogen receptor-positive breast cancer progression is still unclear. Nitric oxide impact on the MCF7 breast cancer line, before and after estrogen-induced apoptosis, was investigated in 3D culture systems using unique live-cell imaging methodologies.

Rh(II)-mediated domino [4 + 1]-annulation of α-cyanothioacetamides using diazoesters: A new entry for the synthesis of multisubstituted thiophenes.

A new approach towards the synthesis of multisubstituted thiophenes is elaborated based on Rh(II)-catalyzed domino reactions of acyclic diazoesters with α-cyanothioacetamides. It provides a way for the preparation of 5-amino-3-(alkoxycarbonylamino)thiophene-2-carboxylates, 2-(5-amino-2-methoxycarbonylthiophene-3-yl)aminomalonates and (2-cyano-5-aminothiophene-3-yl)carbamates with the preparative yields of up to 67%. It was also shown that α-cyanothioacetamides easily interact with dirhodium carboxylates to give rather stable 2:1 complexes, resulting in an evident decrease in the efficiency of the catalytic process at moderate temperatures (20-30 °C).

Distinguishing of 2-MAPB and 6-MAPB: Solution of the problem.

Differentiation of new psychoactive substance (NPS), 6-(2-methylaminopropyl)benzofuran (6-MAPB), and its positional isomer, 2-(2-methylaminopropyl)benzofuran (2-MAPB), by means of gas chromatography/mass spectrometry (GC/MS) with quadrupole detection is ambiguous. Reliable distinguishing of the two isomers could be achieved by MS/MS spectra recorded after collision-induced dissociation (CID) of precursor ions. Both electron ionization (EI) and electrospray ionization (ESI) methods could be used for these purposes.

Mass spectrometric properties of N-(2-methoxybenzyl)-2-(2,4,6-trimethoxyphenyl)ethanamine (2,4,6-TMPEA-NBOMe), a new representative of designer drugs of NBOMe series and derivatives thereof.

Emergence of new psychoactive substances, hallucinogenic phenethylamines in particular, in illicit market is a serious threat to human health in global scale. We have detected and identified N-(2-methoxybenzyl)-2-(2,4,6-trimethoxyphenyl)ethanamine (2,4,6-TMPEA-NBOMe), a new compound in NBOMe series. Identification was achieved by means of gas chromatography/mass spectrometry (GC/MS), including high-resolution mass spectrometry with tandem experiments (GC/HRMS and GC/HRMS ), ultra-high performance liquid chromatography/high-resolution mass spectrometry with tandem experiments (UHPLC/HRMS and UHPLC/HRMS ), and H and C nuclear magnetic resonance spectroscopy.

Hydrogel microstructure live-cell array for multiplexed analyses of cancer stem cells, tumor heterogeneity and differential drug response at single-element resolution.

Specific phenotypic subpopulations of cancer stem cells (CSCs) are responsible for tumor development, production of heterogeneous differentiated tumor mass, metastasis, and resistance to therapies. The development of therapeutic approaches based on targeting rare CSCs has been limited partially due to the lack of appropriate experimental models and measurement approaches. The current study presents new tools and methodologies based on a hydrogel microstructure array (HMA) for identification and multiplex analyses of CSCs.

Synthetic cannabinoid 3-benzyl-5-[1-(2-pyrrolidin-1-ylethyl)-1H-indol-3-yl]-1,2,4-oxadiazole. The first detection in illicit market of new psychoactive substances.

We were the first to detect 3-benzyl-5-[1-(2-pyrrolidin-1-ylethyl)-1H-indol-3-yl]-1,2,4-oxadiazole (given name BzODZ-EPyr) as a new synthetic cannabinoid, in illegal market of new psychoactive compounds (NPS). The compound was known only from pharmaceutical literature so far. BzODZ-EPyr was identified by means of gas chromatography/mass spectrometry (GC/MS) including high resolution mass spectrometry (GC/HRMS), ultra-high performance liquid chromatography/high resolution tandem mass spectrometry (UHPLC/HRMS(2)), Fourier-transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR) (1)H and (13)C.

"What shall I do unto this people?" - BIOETHICAL DILEMMAS IN JEWISH THOUGHT ON MEDICAL RESOURCE ALLOCATION: THE COEXISTENCE OF OPPOSING VIEWS.

Life and death decisions have always been part of the medical profession. Modem discussions on resource allocation in health care deal with such critical situations, and seek ethical solutions that will benefit individuals and society as well as conserve scarce resources. Deontological ethics and utilitarianism are opposing ethical views, each with its own theory on solving moral dilemmas.

Identification and analytical characteristics of synthetic cannabinoids with an indazole-3-carboxamide structure bearing a N-1-methoxycarbonylalkyl group.

Illicit new psychoactive substances (NPS) are a serious threat to health throughout the world. Such NPS do not usually pass preliminary pharmacological trials. In 2014, we identified a series of five new synthetic cannabinoids with an indazole-3-carboxamide structure bearing an N-1-methoxycarbonylalkyl group.

Synthetic cannabinoids as designer drugs: new representatives of indol-3-carboxylates series and indazole-3-carboxylates as novel group of cannabinoids. Identification and analytical data.

By means of gas chromatography with mass spectrometry detection (GC-MS), including high resolution mass spectrometry (GC-HRMS) together with ultra-high performance liquid chromatography in combination with high resolution tandem mass spectrometry (UHPLC-HRMS), nuclear magnetic resonance spectroscopy (NMR) and Fourier transform infrared spectroscopy (FT-IR), structure of new synthetic cannabinoids, representatives of indol- and indazole-3-carboxylates groups, used in smoke mixtures, was determined. Obtained analytical data make reliable identification of these compounds in a course of analysis of criminal seizures possible.

Real-time quantification of protein expression and translocation at individual cell resolution using imaging-dish-based live cell array.

Cell populations represent intrinsically heterogeneous systems with a high level of spatiotemporal complexity. Monitoring and understanding cell-to-cell diversity is essential for the research and application of intra- and interpopulation variations. Optical analysis of live cells is challenging since both adherent and nonadherent cells change their spatial location.

3-Naphthoylindazoles and 2-naphthoylbenzoimidazoles as novel chemical groups of synthetic cannabinoids: chemical structure elucidation, analytical characteristics and identification of the first representatives in smoke mixtures.

By means of gas chromatography with mass spectrometry detection (GC-MS), including high resolution mass spectrometry (GC-HRMS) together with ultra-high performance liquid chromatography in combination with high resolution tandem mass spectrometry (UHPLC-HRMS), nuclear magnetic resonance spectroscopy (NMR) and Fourier transform infrared spectroscopy (FT-IR), structure of novel synthetic cannabinoids, namely, 1-(5-fluoropentyl)-1H-indazol-3-yl(naphthalen-1-yl)methanone, naphthalen-1-yl(1-pentyl-1H-benzo[d]imidazol-2-yl)methanone and 1-(5-fluoropentyl)-1H-benzo[d]imidazol-2-yl(naphthalen-1-yl)methanone was established. Analytical data obtained in the paper enable reliable identification of these compounds during qualitative analysis of seizures, including smoke mixtures.

Donut-shaped chambers for analysis of biochemical processes at the cellular and subcellular levels.

In order to study cell-cell variation with respect to enzymatic activity, individual live cell analysis should be complemented by measurement of single cell content in a biomimetic environment on a cellular scale arrangement. This is a challenging endeavor due to the small volume of a single cell, the low number of target molecules and cell motility. Micro-arrayed donut-shaped chambers (DSCs) of femtoliter (fL), picoliter (pL), and nanoliter (nL) volumes have been developed and produced for the analysis of biochemical reaction at the molecular, cellular and multicellular levels, respectively.

Analytical characterization of some synthetic cannabinoids, derivatives of indole-3-carboxylic acid.

By means of gas chromatography with high resolution mass spectrometry (GC-HRMS), ultra-high performance liquid chromatography in combination with high resolution tandem mass spectrometry (UHPLC-HRMS), nuclear magnetic resonance spectroscopy (NMR) and Fourier transform infrared spectroscopy (FT-IR), structure of a series from a novel synthetic cannabinoids, derivatives of indole-3-carboxylic acid, was established. Methods for determination of the compounds in mixtures, involving chromatographic separation with mass-spectroscopic determination, were elaborated. Analytical data obtained in the paper will make reliable identification of synthetic cannabinoids of the new type during forensic examination possible.

A note on eating disorders and appetite and satiety in the orthodox Jewish meal.

The relationship between religion and eating concerns is receiving increasing empirical attention; and because religion seems to be important to many women with eating concerns, there is an interest in investigating the role religion plays and ways that religion might be employed therapeutically. Research has indicated that women who feel loved and accepted by God are buffered from eating disorder risk factors. An aspect of religiosity that is unique to Judaism is Halakhah, the system of Jewish Law and Ethics which informs the life of a religiously observant orthodox Jew.