The dynamics of hydro-ecological indicators of rivers in the area of placement mining enterprises of region KMA

The results of the comparative analysis of hydro-chemical status of surface water bodies exposing of mining, on the example of the small rivers of the Belgorod region according to the results of the research carried out in 2007-2014 are presented. It is shown that the production of iron mine (Yakovlevsky mine) is influenced on the hydroecological state of the Vorskla river for over 60 k

Pharmacogenetic variability and the probability of site of action target attainment during tuberculosis meningitis treatment: a physiologically based pharmacokinetic modeling and simulations study

Objective and methodsOur objective was to investigate the role of patient pharmacogenetic variability in determining site of action target attainment during tuberculous meningitis (TBM) treatment. Rifampin and isoniazid PBPK model that included SLCO1B1 and NAT2 effects on exposures respectively were obtained from literature, modified, and validated using available cerebrospinal-fluid (CSF) concentrations. Population simulations of isoniazid and rifampin concentrations in brain interstitial fluid and probability of target attainment according to genotypes and M. tuberculosis MIC levels, under standard and intensified dosing, were conducted.ResultsThe rifampin and isoniazid model predicted steady-state drug concentration within brain interstitial fluid matched with the observed CSF concentrations. At MIC level of 0.25 mg/L, 57% and 23% of the patients with wild type and heterozygous SLCO1B1 genotype respectively attained the target in CNS with rifampin standard dosing, improving to 98% and 91% respectively with 35 mg/kg dosing. At MIC level of 0.25 mg/L, 33% of fast acetylators attained the target in CNS with isoniazid standard dosing, improving to 90% with 7.5 mg/kg dosing.ConclusionIn this study, the combined effects of pharmacogenetic and M. tuberculosis MIC variability were potent determinants of target attainment in CNS. The potential for genotype-guided dosing during TBM treatment should be further explored in prospective clinical studies.Pharmacolog

Изотопный состав зимних атмосферных осадков и снежного покрова в предгорьях Алтая

Over the past three decades, several general circulation models of the atmosphere and ocean (atmospheric and oceanic general circulation models  – GCMs) have been improved by modeling the hydrological cycle with the use of isotopologues (isotopes of water) HDO and H2 18O. Input parameters for the GCM models taking into account changes in the isotope composition of atmospheric precipitation were, above all, the results obtained by the network GNIP – Global Network of Isotopes in Precipitation. At different times, on the vast territory of Russia there were only about 40 simultaneously functioning stations where the sampling of atmospheric precipitation was performed. In this study we present the results of the isotope composition of samples taken on the foothills of the Altai during two winter seasons of 2014/15 and 2015/16. Values of the isotope composition of precipitation changed in a wide range and their maximum fluctuations were 25, 202 and 18‰ for δ18О, dexc and δD, respectively. The weighted-mean values of δ18О and δD of the precipitation analyzed for the above two seasons were close to each other (−21.1 and −158.1‰ for the first season and −21.1 and −161.9‰ for the second one), while dexc values differed significantly. The comparison of the results of isotope analysis of the snow cover integral samples with the corresponding in the time interval the weighted-mean values of precipitation showed high consistency. However, despite the similarity of values of δ18О and δD, calculated for precipitation and snow cover, and the results, interpolated in IsoMAP (from data of the GNIP stations for 1960–2010), the dexc values were close to mean annual values of IsoMAP for only the second winter season. According to the trajectory analysis (the HYSPLIT model), the revealed differences between both, the seasons, and the long-term average values of IsoMAP, were associated with a change of main regions where the air masses carrying precipitation were formed, namely, the North Atlantic (the winter season of 2014/15) and the inland areas with open ice-free water bodies (the season of 2015/16). Thus, with the correct interpretation of the results, the data on the snow cover isotope composition on the Altai foothills can be used as an alternative data sources instead of the GNIP data.Приводятся результаты изотопного анализа состава атмосферных осадков и снежного покрова предгорий Алтая. Показано, что средневзвешенные значения осадков двух зимних сезонов (2014/15 и 2015/16 гг.) для δ18О составили −21,1‰, а для δD −158,1 и −161,9‰ соответственно и хорошо согласуются с изотопным составом интегральных проб снежного покрова. Проявившиеся отличия в dexc, очевидно, связаны со сменой основных регионов формирования воздушных масс, приносящих атмосферные осадки: сменой открытых ото льда акваторий Северной Атлантики на внутриконтинентальные водоёмы. При корректной интерпретации результатов данные изотопного состава атмосферных осадков и снежного покрова в предгорьях Алтая могут быть использованы в ряде моделей МОЦ

Mycobacterium tuberculosis Cluster with Developing Drug Resistance, New York, New York, USA, 2003–2009

In 2004, identification of patients infected with the same Mycobacterium tuberculosis strain in New York, New York, USA, resulted in an outbreak investigation. The investigation involved data collection and analysis, establishing links between patients, and forming transmission hypotheses. Fifty-four geographically clustered cases were identified during 2003–2009. Initially, the M. tuberculosis strain was drug susceptible. However, in 2006, isoniazid resistance emerged, resulting in isoniazid-resistant M. tuberculosis among 17 (31%) patients. Compared with patients with drug-susceptible M. tuberculosis, a greater proportion of patients with isoniazid-resistant M. tuberculosis were US born and had a history of illegal drug use. No patients named one another as contacts. We used patient photographs to identify links between patients. Three links were associated with drug use among patients infected with isoniazid-resistant M. tuberculosis. The photographic method would have been more successful if used earlier in the investigation. Name-based contact investigation might not identify all contacts, particularly when illegal drug use is involved

Pre-detection history of extensively drug-resistant tuberculosis in KwaZulu-Natal, South Africa

Antimicrobial-resistant (AMR) infections pose a major threat to global public health. Similar to other AMR pathogens, both historical and ongoing drug-resistant tuberculosis (TB) epidemics are characterized by transmission of a limited number of predominant Mycobacterium tuberculosis (Mtb) strains. Understanding how these predominant strains achieve sustained transmission, particularly during the critical period before they are detected via clinical or public health surveillance, can inform strategies for prevention and containment. In this study, we employ whole-genome sequence (WGS) data from TB clinical isolates collected in KwaZulu-Natal, South Africa to examine the pre-detection history of a successful strain of extensively drug-resistant (XDR) TB known as LAM4/KZN, first identified in a widely reported cluster of cases in 2005. We identify marked expansion of this strain concurrent with the onset of the generalized HIV epidemic 12 y prior to 2005, localize its geographic origin to a location in northeastern KwaZulu-Natal ∼400 km away from the site of the 2005 outbreak, and use protein structural modeling to propose a mechanism for how strain-specific rpoB mutations offset fitness costs associated with rifampin resistance in LAM4/KZN. Our findings highlight the importance of HIV coinfection, high preexisting rates of drug-resistant TB, human migration, and pathoadaptive evolution in the emergence and dispersal of this critical public health threat. We propose that integrating wholegenome sequencing into routine public health surveillance can enable the early detection and local containment of AMR pathogens before they achieve widespread dispersal.The National Institute of Allergy and Infectious Disease and National Institutes of Health.https://www.pnas.orgpm2020Medical Microbiolog

Investigation on Mycobacterium tuberculosis Diversity in China and the Origin of the Beijing Clade

Contains fulltext : 124314.pdf (publisher's version ) (Open Access

Structure-based design of MptpB inhibitors that reduce multi-drug-resistant mycobacterium tuberculosis survival and infection burden in vivo

Mycobacterium tuberculosis protein-tyrosine-phosphatase B (MptpB) is a secreted virulence factor that subverts antimicrobial activity in the host. We report here the structure-based design of selective MptpB inhibitors that reduce survival of multidrug-resistant tuberculosis strains in macrophages and enhance killing efficacy by first-line antibiotics. Monotherapy with an orally bioavailable MptpB inhibitor reduces infection burden in acute and chronic guinea pig models and improves the overall pathology. Our findings provide a new paradigm for tuberculosis treatmen

The dynamics of hydro-ecological indicators of rivers in the area of placement mining enterprises of region KMA

The results of the comparative analysis of hydro-chemical status of surface water bodies exposing of mining, on the example of the small rivers of the Belgorod region according to the results of the research carried out in 2007-2014 are presented. It is shown that the production of iron mine (Yakovlevsky mine) is influenced on the hydroecological state of the Vorskla river for over 60 k

Isotope composition of winter precipitation and snow cover in the foothills of the Altai

Over the past three decades, several general circulation models of the atmosphere and ocean (atmospheric and oceanic general circulation models  – GCMs) have been improved by modeling the hydrological cycle with the use of isotopologues (isotopes of water) HDO and H2 18O. Input parameters for the GCM models taking into account changes in the isotope composition of atmospheric precipitation were, above all, the results obtained by the network GNIP – Global Network of Isotopes in Precipitation. At different times, on the vast territory of Russia there were only about 40 simultaneously functioning stations where the sampling of atmospheric precipitation was performed. In this study we present the results of the isotope composition of samples taken on the foothills of the Altai during two winter seasons of 2014/15 and 2015/16. Values of the isotope composition of precipitation changed in a wide range and their maximum fluctuations were 25, 202 and 18‰ for δ18О, dexc and δD, respectively. The weighted-mean values of δ18О and δD of the precipitation analyzed for the above two seasons were close to each other (−21.1 and −158.1‰ for the first season and −21.1 and −161.9‰ for the second one), while dexc values differed significantly. The comparison of the results of isotope analysis of the snow cover integral samples with the corresponding in the time interval the weighted-mean values of precipitation showed high consistency. However, despite the similarity of values of δ18О and δD, calculated for precipitation and snow cover, and the results, interpolated in IsoMAP (from data of the GNIP stations for 1960–2010), the dexc values were close to mean annual values of IsoMAP for only the second winter season. According to the trajectory analysis (the HYSPLIT model), the revealed differences between both, the seasons, and the long-term average values of IsoMAP, were associated with a change of main regions where the air masses carrying precipitation were formed, namely, the North Atlantic (the winter season of 2014/15) and the inland areas with open ice-free water bodies (the season of 2015/16). Thus, with the correct interpretation of the results, the data on the snow cover isotope composition on the Altai foothills can be used as an alternative data sources instead of the GNIP data

Los clústeres como mecanismo para resolver los problemas socioeconómicos de la Ucrania posterior al conflicto

The purpose of the article was to analyze the cluster strategy in various countries of the world and to highlight the legal instruments that can be used in the process of creation and operation of clusters in Ukraine, taking into account the existing post-conflict socio-economic problems. The research methods used were: analysis, synthesis, consistency, comparison, generalization and prognosis, etc. The main models of cluster development in the world practice are analyzed. The characteristics of the state strategy in the field of regional clustering in the USA, Canada, Italy, Germany, Austria, France, Finland, Japan and China are studied. The authors focused on the legal instruments used in the process of creation and operation of clusters in different countries of the world, which it is advisable to borrow and implement in the Ukrainian legislation. Finally, the following problems of cluster creation in Ukraine have been identified: the lack of a legislative framework; a state strategy to support clusters, as well as incentives for investors. It is concluded that clusters in a difficult socio-economic situation in Ukraine should help to attract investments and develop the economy of regions affected by hostilities.El propósito del artículo fue analizar la estrategia de clústeres en varios países del mundo y resaltar los instrumentos legales que se pueden utilizar en el proceso de creación y operación de clústeres en Ucrania, teniendo en cuenta los problemas socioeconómicos existentes del posconflicto. Los métodos de investigación empleados fueron: análisis, síntesis, consistencia, comparación, generalización y pronóstico, etc. Se analizan los principales modelos de desarrollo de clúster en la práctica mundial. Se estudian las características de la estrategia estatal en el campo de la agrupación regional en EE. UU., Canadá, Italia, Alemania, Austria, Francia, Finlandia, Japón y China. Los autores se centraron en los instrumentos legales utilizados en el proceso de creación y funcionamiento de clústeres en diferentes países del mundo, que es recomendable tomar prestados e implementar en la legislación ucraniana. Finalmente, se han identificado los siguientes problemas de creación de clústeres en Ucrania: la falta de un marco legislativo; una estrategia estatal para apoyar los clústeres, así como incentivos para los inversores. Se concluye que los clústeres en una situación socioeconómica difícil en Ucrania deberían ayudar a atraer inversiones y desarrollar la economía de las regiones afectadas por las hostilidades