Clinical Evaluation of Effectiveness and Safety of Combined Use of Dietary Supplements Amberen® and Smart B® in Women with Climacteric Syndrome in Perimenopause.

INTRODUCTION: Perimenopause is a time of transition in a woman's life that links her reproductive years to the cessation of ovulation, or menopause. For many women, this time is characterized by a variety of physiological and lifestyle changes, including increasing irregularity in menstrual bleeding, frequency and severity of vasomotor symptoms, etc. Therapies evaluated specifically for the perimenopausal women are very limited. This study aimed to evaluate the effectiveness and safety of Amberen® (a succinate-based non-hormonal supplement) combined with a Smart B® (vitamin B) complex in women with typical (without complications) mild to moderate climacteric syndrome during perimenopause. METHODS: Women up to 50 years of age, in perimenopause, with vasomotor and psychosomatic symptoms of the climacteric syndrome were enrolled for the study. The trial was randomized, double-blinded, placebo-controlled, comparative, and prospective. RESULTS: A total of 106 participants were enrolled in the trial and, per protocol, 105 completed the trial. We observed statistically significant improvements in most of the Greene Climacteric Scale symptoms, State-Trait Anxiety Inventory (STAI), Hospital Anxiety and Depression Scale (HADS), and Well-being, Activity, and Mood (WAM) scores. The intervention was well tolerated with few adverse effects reported to be mild and transient. CONCLUSION: The use of this dietary supplement is safe and eliminates or improves vasomotor and psychosomatic symptoms of climacteric symptoms in perimenopausal women: it improves sleep and cognitive abilities, lowers depression and anxiety, improves mood and well-being, and positively affects quality of life. GOV IDENTIFIER: NCT03897738.

Gandhia gen. nov.-A New Diatom Genus with Unusual Morphology Split Off from the Genus Navicula Bory.

A new naviculoid diatom genus, Gandhia gen. nov., was described based on a detailed morphological investigation using light and scanning electron microscopy. Gandhia obtecta (Jüttner and Cox) Kulikovskiy, Glushchenko, Iurmanov, M.Thacker, B.Karthick and Kociolek comb. nov. was previously described as a member of the genus Navicula Bory sensu lato. This species differs from other species in the genus Navicula s.l. by the presence of an internal siliceous lamina covering the alveoli and forming the image of longitudinal lines on either side of the axial area, visible in LM. The presence of this siliceous lamina is similar to laminae in genera such as Pinnularia and Gomphoneis. This unusual morphology is not typical for Navicula sensu stricto, as previously noted by other scientists. Additional investigation of Gandhia obtecta comb. nov. and Gandhia ramosissimoides (H.P. Gandhi) Kulikovskiy, Glushchenko, M.Thacker, B.Karthick and Kociolek comb. nov. from waterbodies of the Western Ghats and the Himalayan region was conducted. Comparison with other species with the same morphological features included two additional species in the genus, namely, Gandhia jakovljevicii (Hustedt) Kulikovskiy, Glushchenko, M.Thacker, B.Karthick, and Kociolek comb. nov. and Gandhia lucida (Pantocsek) Kulikovskiy, Glushchenko, M.Thacker, B.Karthick and Kociolek comb. nov. We discuss the biogeographic patterns of the species, including disjuncts between Europe and Asia.

Is Sellaphora the New Navicula? Cymbosellaphora (Cymbellales), a New Genus Based on Taxa Previously Assigned to Sellaphora.

A new diatom genus Cymbosellaphora Kulikovskiy, Glushchenko, Genkal and Kociolek gen. nov., was described with species Cymbosellaphora vietnamensis Glushchenko, Kulikovskiy and Kociolek sp. nov. C. vietnamensis sp. nov. was described from Vietnam and characterized by the presence of morphological features such as valves with naviculoid symmetry, slight dorsiventrality, the presence of tectula as pore occlusions, uniseriate striae, and a very broad mantle. Four species were transferred to the new genus. These are C. absoluta comb. nov., C. circumborealis comb. nov., C. geisslerae comb. nov., and C. laterostrata comb. nov. Previously, these species were members of genera Navicula Bory, Sellaphora Mereschkowsky, and Naviculadicta Lange-Bertalot. The taxonomic history of these species and genera are discussed. The tectulum is known only from the cymbelloid diatoms, and our new genus is placed within the Cymbellaceae. The presence of a tectulum demonstrates that these species cannot be placed in Sellaphora, as indicated in the literature. The recent proposal to transfer a large number of species with different morphologies to the genus Sellaphora is also discussed. Additionally, we compare pore occlusions with tectula between different genera of the Cymbellaceae with naviculoid symmetry.

New and Interesting Taxa from the Diatom Genus Gomphonema Ehrenberg in Shallow, Nearshore Sites on the Eastern Coast of Lake Baikal.

During this investigation, sixteen species from the genus Gomphonema were found in a shallow bay (near Oimur, Kabansky District) located on the eastern shore of Lake Baikal. Eleven of these taxa have been described previously. Five species are described as new to science. We provide ecological information about these Gomphonema species, including their distribution within and outside Lake Baikal, and compare and contrast the new taxa with morphologically similar congeners. The diversity of morphologies present in Lake Baikal among the Gomphonema species suggests there has been both in-lake speciation as well as the introduction of various groups of species. The idea that Lake Baikal may support a high number of endemics by their partitioning niches based on depth is supported by the different groups of gomphonemoid diatoms present.

Molecular and Morphological Investigations of Two Giant Diatom Cymbella Species from the Transbaikal Area (Russia, Siberia) with Comments on Their Distributions.

For the first time, a giant diatom species of the genus Cymbella from Lake Baikal was studied using molecular methods. Molecular and morphological investigations allowed to us to described one new species, Cymbella baicalaspera Glushchenko, Kulikovskiy and Kociolek sp. nov. This species is both morphologically similar and phylogenetically close to a second giant Cymbella species that we investigated here, identified by us as Cymbella himalaspera Jüttner and Van de Vijver in Jüttner et al. 2010. This species was first described from Nepal on the basis of a morphological investigation. Small morphological differences exist between the type population and specimens from Lake Baikal, but otherwise the two are identical. These very interesting results show that some Baikalian diatoms can be distributed more widely and are not only endemic to this ancient lake. Similarity between Cymbella baicalaspera sp. nov. and Cymbella himalaspera on the basis of both morphological features and their close phylogenetic relationships suggested by molecular data indicate they are sister species and an example of sympatric speciation. These results also suggest an early development of a species flock. This species group warrants additional research in terms of. their diversification and biogeography.

Planoplatessa gen. nov.-A New, Neglected Monoraphid Diatom Genus with a Cavum.

A new monoraphid diatom genus, Planoplatessa gen. nov., is described on the basis of a detailed morphological investigation using light and scanning electron microscopy. We transferred Achnanthes joursacensis Héribaud, a species described from fossil deposits in France, to our new genus. We investigated material from Mongolia from Recent populations. This taxon is known from fossils to Recent across the Holarctic. Achnanthes joursacensis was previously transferred to the genera Planothidium and Platessa, but the morphology of A. joursacensis does not share all morphological features with these two genera. We discuss important morphological features for the delimitation of monoraphid genera based on careful morphological and molecular investigations we presented previously. Planoplatessa gen. nov. as a genus is characterized by having uniseriate striae on both the raphe and the rapheless valves, a cavum in rapheless valves only, and straight distal raphe ends on the valve face.

Two new species of Navicula (Bacillariophyta) from Southeast Asia.

We present light and scanning electron microscopical observations on two new species of Navicula Bory sensu stricto from Southeast Asia. Naviculawinoniformis Chudaev, Glushchenko, Kulikovskiy & Kociolek, sp. nov. differs from taxa with similar outline and size by the combination of simple drop-like external raphe endings deflected to the primary valve side, presence of well-developed external longitudinal grooves and relatively low lineolae density. Naviculasparsilineolata Chudaev, Glushchenko, Kulikovskiy & Kociolek, sp. nov. can be discriminated from the taxa of similar valve shape and size by consistently lower lineolae density, and from the majority of them also by the structure of external proximal raphe endings with small projections in proximal parts and larger triangular insertions in distal parts. Some remarks on Navicula species diversity and its distribution in the Southeast Asia are given.

Achnanthidium tinea sp. nov. - a new monoraphid diatom (Bacillariophyceae) species, described on the basis of molecular and morphological approaches.

A new monoraphid diatom species Achnanthidium tinea Tseplik, Kulikovskiy, Kociolek & Maltsev, sp. nov. is described from Indonesia. The species is described on the basis of molecular and morphological analyses. According to molecular data the new species belongs to the clade that includes strains of Achnanthidium minutissimum, Achnanthidium saprophilum and Achnanthidium digitatum. Morphologically, the new species differs quite significantly from other species of the same genus because of linear-elliptic valves with almost parallel sides and strongly radiate striae and a butterfly-shaped fascia on the raphe valve. The morphology and phylogeny of the new species are discussed, and thoughts on the current state of the taxonomy of the genus Achnanthidium are expressed. Our work shows the importance of using molecular data in diatom systematics and also demonstrates the need to investigate rarely studied regions of our planet.

Preoperative Typing of Thyroid and Parathyroid Tumors with a Combined Molecular Classifier.

In previous studies, we described a method for detecting and typing malignant tumors of the thyroid gland in fine-needle aspiration biopsy samples via analysis of a molecular marker panel (normalized HMGA2 mRNA level; normalized microRNA-146b, -221, and -375 levels; mitochondrial-to-nuclear DNA ratio; and BRAFV600E mutation) in cytological preparations by quantitative PCR. In the present study, we aimed to estimate the specificity of the typing of different thyroid tumors by the proposed method. Fine-needle aspiration cytological preparations from 278 patients were used. The histological diagnosis was known for each sample. The positive and negative predictive values of the method assessed in this study were, respectively, 100% and 98% for papillary thyroid carcinoma (n = 63), 100% and 100% for medullary thyroid carcinoma (n = 19), 43.5% and 98% for follicular carcinoma (n = 15), and 86% and 100% for Hürthle cell carcinoma (n = 6). Thus, we demonstrate that the diagnostic panel, including the analysis of microRNA expression, mRNA expression, the BRAFV600E mutation, and the mitochondrial-to-nuclear DNA ratio, allows the highly accurate identification of papillary thyroid carcinoma, medullary thyroid carcinoma, and Hürthle cell carcinoma but not malignant follicular tumors (positive predictive value was below 50%).

Achnanthidiumgladius sp. nov. (Bacillariophyceae) - a new monoraphid diatom species from Indonesia.

A new monoraphid diatom species Achnanthidiumgladius sp. nov. is described from Indonesia. The description is based on molecular data (18SV4), morphological analysis and comparison with similar species. According to molecular data, Achnanthidiumgladius sp. nov. is closely related to Achnanthidiumminutissimum. Morphologically, the new species differs from similar species by the absence of a fascia on raphe valve, cell size, and striae density and pattern. The new species is only known from the type locality in Indonesia. Comparison with close related species is given.

Four new species from the diatom (Bacillariophyceae) genus Adlafia Moser, Lange-Bertalot & Metzeltin from waterbodies of Vietnam.

Four species of the diatom genus Adlafia were found from waterbodies of Vietnam and described as new to science. Their formal descriptions are presented herein and they are illustrated by light and scanning electron micrographs. These new species are: A. lamdongiensis Glushch., Kulik. & Kociolek, sp. nov., A. babeiensis Glushch., Kulik. & Kociolek, sp. nov., A. vietnamensis Glushch., Kulik. & Kociolek, sp. nov. and A. dauiensis Glushch., Kulik. & Kociolek, sp. nov. These species are then compared to other similar taxa. Our new findings add to the number of species in this interesting genus and contribute to our understanding of the unique diatom flora found in Vietnam.

Succinate-Based Dietary Supplement for Menopausal Symptoms: A Pooled Analysis of Two Identical Randomized, Double-Blind, Placebo-Controlled Clinical Trials.

BACKGROUND: To evaluate the efficacy of a succinate-based dietary supplement (SBDS; Amberen) in symptomatic menopausal women using a larger sample size derived by pooling data from two identical trials. METHODS: Raw data were pooled from two identical randomized, multicenter, double-blinded, placebo-controlled, 90-day clinical trials. Women aged 42-60 years with mild to moderate vasomotor and psychosomatic menopausal symptoms were included (114 in the treatment group and 113 in the placebo group). Symptoms were assessed by the Greene Climacteric Scale and State-Trait Anxiety Inventory. Changes in body mass index, body weight, waist and hip circumferences, and plasma levels of follicle stimulating hormone, luteinizing hormone, estradiol, leptin, and apolipoproteins A1 and B were also evaluated. RESULTS: SBDS use resulted in significant improvements in several endpoints including alleviation of 16 of 21 menopausal symptoms (p ≤ 0.05, Greene Scale) and a decrease in anxiety (p < 0.0001, State-Trait Anxiety Inventory) when compared to placebo. Significant reductions were observed in weight, body mass index, and waist and hip circumferences in the supplement cohort. Evaluation of physiological parameters showed a significant increase in serum estradiol levels compared to baseline (p < 0.0001) among users of the SBDS. Levels of follicle stimulating hormone and luteinizing hormone decreased slightly in both groups, without significant differences between the groups. Leptin levels decreased with statistical significance in the SBDS cohort compared to placebo (p=0.027). For those with initial leptin concentrations above the reference range, leptin decreased significantly in the SBDS group compared to the baseline (p < 0.0001) and to placebo (p=0.027). CONCLUSIONS: The pooled analysis reaffirms the outcomes from the individual trials. A nonhormonal, succinate-based dietary supplement is shown to relieve menopausal symptoms when compared to a placebo regimen in a randomized, double-blinded clinical trial.

Phylogenetic analysis of Bacillus anthracis strains from Western Siberia reveals a new genetic cluster in the global population of the species.

BACKGROUND: Anthrax is a zoonotic disease caused by the gram-positive bacterium Bacillus anthracis. The most anthrax-endemic regions of Russia are Siberia and North Caucasus. Previously, genotyping of Russian B.anthracis isolates was carried out using canSNP and MLVA data; these methods yield lower resolution results compared to whole genome SNP analysis (wgSNP). In this research, we have used wgSNP method for genotyping of 10 B.anthracis isolates, obtained during 1961-2016 in Russia on territory of Western Siberia. RESULTS: We have analyzed 185 B.anthracis genomes available in GenBank database and genomes of 10 isolates obtained in this study to determine the place of Russian isolates in the global phylogeny of B.anthracis. For the studied genomes we have detected 7203 SNPs, which were used for building a phylogenetic reconstruction with Maximum Likelihood Method. Results of the phylogenetic analysis indicate that Russian strains belong to three different genetic groups. Three strains belong to genetic group "Ames", two strains - to "STI" group. Five strains belong to the main genetic line B, and four of them form a subcluster, described for the first time, which we have named "Siberia". CONCLUSIONS: In this study, the data on genetic diversity of B.anthracis strains on the territory of Western Siberia is presented for the first time. As a result of complex phylogenetic analysis, the place of these isolates was determined in the global phylogenetic structure of the B.anthracis population. We describe a new cluster in the main genetic line B for the first time.

Genotyping and phylogenetic location of one clinical isolate of Bacillus anthracis isolated from a human in Russia.

BACKGROUND: Anthrax is a zoonotic disease caused by the Gram-positive bacterium Bacillus anthracis. In Russia, there are more than 35 thousand anthrax stationary unfavourable sites. At the same time, there is very little published information about the isolates of B. anthracis from the territory of Russia. In this study, we report the use of whole genome sequencing (WGS) and bioinformatics analysis to characterize B. anthracis 81/1 strain isolated in Russia in 1969 from a person during an outbreak of the disease in the Stavropol region. RESULTS: We used 232 B. anthracis genomes, which are currently available in the GenBank database, to determine the place of the Russian isolate in the global phylogeny of B. anthracis. The studied strain was characterized by PCR-based genetic methods, such as Multiple-Locus Variable-Number Tandem Repeat Analysis (MLVA), canonical single nucleotide polymorphisms (canSNP), as well as the method of full-genomic analysis of nucleotide polymorphisms (wgSNP). The results indicate that the Russian B. anthracis 81/1 strain belongs to Trans-Eurasion (TEA) group, the most representative in the world. CONCLUSIONS: In this study, the full genomic sequence of virulent B. anthracis strain from Russia was characterized for the first time. As a result of complex phylogenetic analysis, the place of this isolate was determined in the global phylogenetic structure of the B. anthracis population, expanding our knowledge of anthrax phylogeography in Russia.

Omega-3 Long-Chain Polyunsaturated Fatty Acids and Preeclampsia: Trials Say "No," but Is It the Final Word?

Preeclampsia is a dangerous disorder of pregnancy, defined as hypertension with proteinuria. Its nature remains elusive, and measures of prevention and treatment are limited. Observational studies have suggested that preeclampsia is associated with low intake of omega-3 long-chain polyunsaturated fatty acids (LCPUFA). In recent decades, researchers studied LCPUFA supplementation as a measure to prevent preeclampsia. Most of these trials and later systematic reviews yielded negative results. However, these trials had several important limitations associated with heterogeneity and other issues. Recent research suggests that preeclampsia trials should take into consideration the gender of the fetus (and thus sexual dimorphism of placenta), the positive effect of smoking on preeclampsia prevalence, and the possibility that high doses of LCPUFA mid-term or later may promote the disorder instead of keeping it at bay. In this review, we discuss these issues and future prospects for LCPUFA in preeclampsia research.

Design, synthesis and biological evaluation of novel 5-oxo-2-thioxoimidazolidine derivatives as potent androgen receptor antagonists.

A series of novel highly active androgen receptor (AR) antagonists containing spiro-4-(5-oxo-3-phenyl-2-thioxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile core was designed based on the SAR studies available from the reported AR antagonists and in silico modeling. Within the series, compound (R)-6 (ONC1-13B) and its related analogues, including its active N-dealkylated metabolite, were found to be the most potent molecules with the target activity (IC50, androgen-sensitive human PCa LNCaP cells) in the range of 59-80 nM (inhibition of PSA production). The disclosed hits were at least two times more active than bicalutamide, nilutamide and enzalutamide within the performed assay. Several compounds were classified as partial agonists. Hit-compounds demonstrated benefit pharmacokinetic profiles in rats. Comparative SAR and 3D molecular docking studies were performed for the hit compounds elucidating the observed differences in the binding potency.

Discovery of novel highly potent hepatitis C virus NS5A inhibitor (AV4025).

A series of next in class small-molecule hepatitis C virus (HCV) NS5A inhibitors with picomolar potency containing 2-pyrrolidin-2-yl-5-{4-[4-(2-pyrrolidin-2-yl-1H-imidazol-5-yl)buta-1,3-diynyl]phenyl}-1H-imidazole cores was designed based on the SAR studies available for the reported NS5A inhibitors. Compound 13a (AV4025), with (S,S,S,S)-stereochemistry (EC50 = 3.4 ± 0.2 pM, HCV replicon genotype 1b), was dramatically more active than were the compounds with two (S)- and two (R)-chiral centers. Human serum did not significantly reduce the antiviral activity (<4-fold). Relatively favorable pharmacokinetic features and good oral bioavailability were observed during animal studies. Compound 13a was well tolerated in rodents (in mice, LD50 = 2326 mg/kg or higher), providing a relatively high therapeutic index. During safety, pharmacology and subchronic toxicity studies in rats and dogs, it was not associated with any significant pathological or clinical findings. This compound is currently being evaluated in phase I/II clinical trials for the treatment of HCV infection.