2-(1H-Pyrazol-4-yl)acetic acids as CRTh2 antagonists

High throughput screening identified the pyrazole-4-acetic acid substructure as CRTh2 receptor antagonists. Optimisation of the compounds uncovered a tight SAR but also identified some low nanomolar inhibitors.     

Lipidomics Reveals Early Metabolic Changes in Subjects with Schizophrenia: Effects of Atypical Antipsychotics

There is a critical need for mapping early metabolic changes in schizophrenia to capture failures in regulation of biochemical pathways and networks. This information could provide valuable insights about disease mechanisms, trajectory of disease progression, and diagnostic biomarkers. We used a lipidomics platform to measure individual lipid species in 20 drug-naïve patients with a first episode of schizophrenia (FE group), 20 patients with chronic schizophrenia that had not adhered to prescribed medications (RE group), and 29 race-matched control subjects without schizophrenia. Lipid metabolic profiles were evaluated and compared between study groups and within groups before and after treatment with atypical antipsychotics, risperidone and aripiprazole. Finally, we mapped lipid profiles to n3 and n6 fatty acid synthesis pathways to elucidate which enzymes might be affected by disease and treatment. Compared to controls, the FE group showed significant down-regulation of several n3 polyunsaturated fatty acids (PUFAs), including 20:5n3, 22:5n3, and 22:6n3 within the phosphatidylcholine and phosphatidylethanolamine lipid classes. Differences between FE and controls were only observed in the n3 class PUFAs; no differences where noted in n6 class PUFAs. The RE group was not significantly different from controls, although some compositional differences within PUFAs were noted. Drug treatment was able to correct the aberrant PUFA levels noted in FE patients, but changes in re patients were not corrective. Treatment caused increases in both n3 and n6 class lipids. These results supported the hypothesis that phospholipid n3 fatty acid deficits are present early in the course of schizophrenia and tend not to persist throughout its course. These changes in lipid metabolism could indicate a metabolic vulnerability in patients with schizophrenia that occurs early in development of the disease.     

A Systematic Review of the Relationships between Intimate Partner Violence and HIV/AIDS

Background

Intimate partner violence (IPV) is a significant health problem that has been associated with HIV infection in numerous studies. We aimed to systematically review the literature on relationships between IPV and HIV in order to describe the prevalence of IPV in people with HIV, the prevalence of HIV in people experiencing IPV, the association between IPV and HIV, and evidence regarding mechanisms of risk and interventions.

Methods

Data sources were 10 electronic databases and reference lists. Studies were included if they reported data on the relationship between IPV and HIV. All records were independently reviewed by two authors at the stages of title and abstract review and full text review. Any abstract considered eligible by either reviewer was reviewed in full, and any disagreement regarding eligibility of full texts or data extracted was resolved by discussion.

Results

101 articles were included. Experiencing IPV and HIV infection were associated in unadjusted analyses in most studies, as well as in adjusted analyses in many studies. The findings of qualitative and quantitative studies assessing potential mechanisms linking IPV and HIV were variable. Few interventions have been assessed, but two identified in this review were promising in terms of preventing IPV, though not HIV infection.

Conclusions

Experiencing IPV and HIV infection tend to be associated in unadjusted analyses, suggesting that IPV screening and linkage with relevant programs and services may be valuable. It is unclear whether there is a causal association between experiencing IPV and HIV infection. Research should focus on defining parameters of IPV which are relevant to HIV infection, including type of IPV and period of exposure and risk, on assessing potential mechanisms, and on developing and assessing interventions which build on the strengths of existing studies.     

Detection of Anorectal and Cervicovaginal Chlamydia Trachomatis Infections following Azithromycin Treatment: Prospective Cohort Study with Multiple Time-Sequential Measures of rRNA,DNA, Quantitative Load and Symptoms

Background

Determination of Chlamydia trachomatis (Ct) treatment success is hampered by current assessment methods, which involve a single post-treatment measurement only. Therefore, we evaluated Ct detection by applying multiple laboratory measures on time-sequential post-treatment samples.

Methods

A prospective cohort study was established with azithromycin-treated (1000 mg) Ct patients (44 cervicovaginal and 15 anorectal cases). Each patient provided 18 self-taken samples pre-treatment and for 8 weeks post-treatment (response: 96%; 1,016 samples). Samples were tested for 16S rRNA (TMA), bacterial load (quantitative PCR; Chlamydia plasmid DNA) and type (serovar and multilocus sequence typing). Covariates (including behavior, pre-treatment load, anatomic site, symptoms, age, and menstruation) were tested for their potential association with positivity and load at 3–8 weeks using regression analyses controlling for repeated measures.

Findings

By day 9, Ct positivity decreased to 20% and the median load to 0.3 inclusion-forming units (IFU) per ml (pre-treatment: 170 IFU/ml). Of the 35 cases who reported no sex, sex with a treated partner or safe sex with a new partner, 40% had detection, i.e. one or more positive samples from 3–8 weeks (same Ct type over time), indicating possible antimicrobial treatment failure. Cases showed intermittent positive detection and the number of positive samples was higher in anorectal cases than in cervicovaginal cases. The highest observed bacterial load between 3–8 weeks post-treatment was 313 IFU/ml, yet the majority (65%) of positive samples showed a load of ≤2 IFU/ml. Pre-treatment load was found to be associated with later load in anorectal cases.

Conclusions

A single test at 3–8 weeks post-treatment frequently misses Ct. Detection reveals intermittent low loads, with an unknown risk of later complications or transmission. These findings warrant critical re-evaluation of the clinical management of single dose azithromycin-treated Ct patients and fuel the debate on defining treatment failure. Clinicaltrials.gov Identifier: NCT01448876.     

Distribution of rheophil benthos in the mountainous rivers of Tuva with subaerial deltas

The formation and distribution of the benthos population of amphibiotic insects, mainly mayflies (Ephemeroptera) and stoneflies (Plecoptera), inhabiting minor rivers with subaerial deltas have been studied in Central Tuva as an example. It has been revealed that the life of biota, first and foremost benthos, is a complex combination of migration processes, drift, and redrift of the unevenly aged larva of amphibiotic insects, which demonstrate a certain seasonal confinement to various parts of these rivers along their channels coinciding with the seasonal dynamics of watering and food capacity.     

Ecology of yellow wagtail (Motacilla flava L.) in the forest tundra of Western Siberia and factors limiting its northward rage expansion

Based on the long-term studies of the ecology of yellow wagtail in the Lower Ob region and the experimental results, factors determining the penetration of this species into the tundra of the Yamal Peninsula have been analyzed.     

Impact of technogenic systems on the environment and human health in the priamurye and primorye territories

This paper discusses the results of studying the technogenic contamination of ecosystems with the waste of placer gold production in the Priamurye and Primorye territories. Environmental objects were shown to degrade and there was a sharp deterioration in human habitats, posing a threat to human life in mining settlements. Measures for reducing the negative impact of the waste on environmental objects are proposed.     

A model for the hydrological cycle of a forested catchment and assessment of the changes caused in water balance by cuttings

A physicomathematical model of the hydrological cycle in a forested catchment was constructed. This model describes the interception of liquid and solid precipitation by tree crowns; snow accumulation and melting; vertical transfer of moisture in soil and its evaporation; and surface, subsurface, and channeled runoffs. The model was calibrated and verified using the observation data for the completely forested Taezhnyi catchment within the area of the Valdai Water Balance Station. Then the model was used to assess possible changes in the hydrological cycle after clear cuttings in this catchment. The values of model parameters were compared to the corresponding soil characteristics in the adjacent treeless (field) Usad’evskii catchment. Modeling results demonstrate that the average water reserve in the snow cover before melting can increase by 15% after forest cutting in the Taezhnyi catchment. The losses for snow sublimation are reduced almost two-fold. The snow melting intensity increases by 30% and its duration decreases by 10 days. The annual runoff after cutting increases by 7–10%; however, the seasonal distribution of the runoff and the constituents of the water balance change to a greater degree. During spring flood, the maximal water discharge in the forested catchment is 50% smaller than after forest cutting. The duration of spring flood after cutting is reduced by 5–7 days. The changes in the hydrological cycle depending on the age-related alteration in leaf area index were also studied.     

Forests as a national treasure of Russia

This paper analyzes the future of the Russian forest. Its preservation determines, to a large extent, the ethical, economic, and ecological environment of our country. The authors support the idea of a forest being not only a storage place for timber, but a specific state property that, besides its value as raw material, has an enormous ecological and social weight, since it represents a living environment for certain peoples of Russia. The ineffectiveness of the existing forest legislation in Russia was proved through the examples of forest fires. Concrete legislative and administrative solutions are proposed.     

Pyrogenic changes in microelement content in soils and plants from the pine forests of western Transbaikal

The pyrogenic transformation of the microelement content in soils and plants from western Transbaikal (Republic of Buryatia) has been studied. As is found, ground fires, under the studied conditions, lead to the transformation of soil properties and slightly elevated concentrations of Mn, Zn, Cu, and Pb in the surface soil (0–40 cm) and and Mn, Zn, and Pb in plants. It has been also found that the soil Fe: Mn ratio becomes lower. A pyrogenic transformation of vegetation and the soil properties, the elemental composition in particular, is shown to be traced over several years after the fire.