Supramolecular D⋯A-layered structures based on germanium complexes with 2,3-dihydroxynaphthalene and N,N′-bidentate ligands

The concept of using redox-active ligands, which has become extremely widespread in organometallic chemistry, is often considered from ‘their effect on the metal center properties’ point of view and ‘how to modify the ligands’. In this paper, we present the reverse side of this effective approach – a dramatic change of redox properties of ligands under the influence of a redox-inert metal. Germanium derivatives based on 2,3-dihydroxynaphthalene (1) and N,N′-bidentate ligands, namely 2,2′-bipyridine (2) and 1,10-phenanthroline (3), were obtained and characterized by CV, UV-vis spectroscopy, DFT calculations and in the case of 3 X-ray diffraction. It was shown that the HOMO of the complexes is almost completely located on the naphthalene fragment while the LUMO is on the N,N-ligands. At the same time, there are no boundary molecular orbitals on the germanium atom, but it forms the axial part of the molecule holding two opposite motifs together. Moreover, it sharply affects the level of HOMO and LUMO. Derivatives 2 and 3 are more easily oxidized compared to 2,3-dihydroxynaphthalene by 0.31–0.34 V (7–8 kcal mol⁻¹) and are more easily reduced compared to N,N-donors by 1.08–1.15 V (25–26.5 kcal mol⁻¹). All this together makes it possible to form a system with a narrow HOMO/LUMO gap (∼2 eV). The crystal structure of 3 consists of alternating monomolecular easily oxidizing and easily reducing layers formed due to intermolecular interactions, in particular π-stacking. In addition, in contrast to 1 that starts to decompose noticeably at the temperatures from 200 °C, 2 and 3 have an extremely high thermal stability. They remain stable with no signs of decomposition and melting up to 400 °С. We believe that this approach to the formation of the supramolecular structure may present prospects for obtaining new functional materials.

The concept of using redox-active ligands is often considered from ‘their effect on the metal center properties’ point of view. We present the reverse side of this approach – change of redox properties of ligands under the influence of metal.     

Two general methods for population pharmacokinetic modeling: non-parametric adaptive grid and non-parametric Bayesian

Population pharmacokinetic (PK) modeling methods can be statistically classified as either parametric or nonparametric (NP). Each classification can be divided into maximum likelihood (ML) or Bayesian (B) approaches. In this paper we discuss the nonparametric case using both maximum likelihood and Bayesian approaches. We present two nonparametric methods for estimating the unknown joint population distribution of model parameter values in a pharmacokinetic/pharmacodynamic (PK/PD) dataset. The first method is the NP Adaptive Grid (NPAG). The second is the NP Bayesian (NPB) algorithm with a stick-breaking process to construct a Dirichlet prior. Our objective is to compare the performance of these two methods using a simulated PK/PD dataset. Our results showed excellent performance of NPAG and NPB in a realistically simulated PK study. This simulation allowed us to have benchmarks in the form of the true population parameters to compare with the estimates produced by the two methods, while incorporating challenges like unbalanced sample times and sample numbers as well as the ability to include the covariate of patient weight. We conclude that both NPML and NPB can be used in realistic PK/PD population analysis problems. The advantages of one versus the other are discussed in the paper. NPAG and NPB are implemented in R and freely available for download within the Pmetrics package from www.lapk.org.     

Oriented conjugates of single-domain antibodies and quantum dots: toward a new generation of ultrasmall diagnostic nanoprobes

Common strategy for diagnostics with quantum dots (QDs) utilizes the specificity of monoclonal antibodies (mAbs) for targeting. However QD-mAbs conjugates are not always well-suited for this purpose because of their large size. Here, we engineered ultrasmall nanoprobes through oriented conjugation of QDs with 13-kDa single-domain antibodies (sdAbs) derived from llama IgG. Monomeric sdAbs are 12 times smaller than mAbs and demonstrate excellent capacity for refolding. sdAbs were tagged with QDs through an additional cysteine residue integrated within the C terminal of the sdAb. This approach allowed us to develop sdAbs-QD nanoprobes comprising four copies of sdAbs coupled with a QD in a highly oriented manner. sdAbs-QD conjugates specific to carcinoembryonic antigen (CEA) demonstrated excellent specificity of flow cytometry quantitative discrimination of CEA-positive and CEA-negative tumor cells. Moreover, the immunohistochemical labeling of biopsy samples was found to be comparable or even superior to the quality obtained with gold standard protocols of anatomopathology practice. sdAbs-QD-oriented conjugates as developed represent a new generation of ultrasmall diagnostic probes for applications in high-throughput diagnostic platforms. FROM THE CLINICAL EDITOR: The authors report the development of sdAbs-QD-oriented conjugates, comprised of single domain antibodies that are 12 times smaller than regular mAb-s and quantum dots. These ultrasmall diagnostic probes represent a new generation of functionalized ODs for applications in high-throughput diagnostic platforms.     

Research into the Strength of an Open Wagon with Double Sidewalls Filled with Aluminium Foam

The research is concerned with the use of double walls filled with aluminium foam for an open wagon in order to decrease the dynamic stresses during the operational modes. The research presents the strength calculation for the bearing structure of an open wagon with consideration of the engineering solutions proposed. It was found that the maximum equivalent stresses appeared in the bottom section of the centre sill behind the back support; they amounted to about 315 MPa and did not exceed the allowable values. The maximum displacements were detected in the middle section of the centre sill and amounted to 9.6 mm. The maximum deformations were 1.17 × 10⁻². The research also presents the strength calculation for a weld joint in the maximum loaded zones of the bearing structure of an open wagon and gives the results of a modal analysis of the bearing structure of the improved open wagon. It was found that the critical oscillation frequencies did not exceed the allowable values. The results of the research may be useful for those who are concerned about designing innovative rolling stock units and improving the operational efficiency of railway transport.     

The potential for bridging: HIV status awareness and risky sexual behaviour of injection drug users who have non-injecting permanent partners in Ukraine

Objective

To quantify potential bridging of HIV transmission between the injection drug using subpopulation to the non-injection drug using population through unprotected heterosexual sex.

Design

Secondary analysis of cross-sectional data.

Methods

A sub-sample of participants who reported having a permanent partner who are not injection drug users and have not injected drugs in the past (N=1379) was selected from a survey implemented in 26 Ukrainian cities in 2011. This study evaluates the association between consistent condom use and awareness of HIV status as measured by rapid testing during the study (known/unknown HIV+, known/unknown HIV− and undetermined) among a sub-sample of male injection drug users (IDUs) who have a non-injecting permanent partner. Poisson regression, with robust variance estimates, was utilized to identify associations while adjusting for other factors.

Results

Reported consistent condom use varied between 15.5% (unknown HIV−) and 37.5% (known HIV+); average use was 19.3%. In multivariate analysis, males who were aware of their HIV+ status were more likely to report recent consistent condom use compared to those who were unaware of their HIV+ status. This association remains after adjustment for age, region, education level, years of injection, alcohol use, self-reported primary drug use and being an NGO client (prevalence ratio=1.65; 95% CI 1.03–2.64). No such association was found for those who were HIV−.

Conclusions

Our results regarding HIV-positive male IDUs reinforce previous findings that HIV testing and counselling may be an effective means of secondary prevention. Further research is needed to understand how to effectively promote safer sex behaviours for IDUs who are currently HIV−.     

Non-inferiority of short-term urethral catheterization following fistula repair surgery: study protocol for a randomized controlled trial

Background

Contraception is a major component of reproductive health. Assessing the levels of contraceptive awareness and use helps to identify potential areas of intervention. Hence, this study was conducted to assess awareness, practice and associated factors of modern contraceptives among street women in North-West Ethiopia.

Methods

A cross-sectional study was conducted on 204 street women from Gondar and Bahir Dar cities. Participants were recruited from “cluster” sites such as main road sides, isolated slum areas, around Churches and/or Mosques (in the mornings of Sundays and other religious feast days) and streets where street women usually reside and/or sleep. Data were collected using a pre-tested and structured interview questionnaire in local language (Amharic) after informed verbal consent. Data were then entered into SPSS version 16.0 for analysis. Binary logistic regression models were fit to assess associations and control confounding. Associations were measured by the Odds ratio and its 95% confidence interval.

Results

The mean (±SD) age of participants was 30.9 (± 8.7) years. Majority (90.7%) had ever heard about modern contraceptives. Nearly half (47.1%) had ever used and a third (34.3%) were current users. Three quarter of the current users (74.3%) were using injectables while 10% were on long acting or permanent methods. Marital status (AOR=2.81), family size (AOR=2.67) and age of 25–34 years (AOR=3.45) were associated with modern contraceptive use.

Conclusions

Current contraceptive use among street women is satisfactory considering their life styles and living conditions. However, further research is required to explain perceptions and hidden barriers.     

In their own voices: Breaking the vicious cycle of addiction,treatment and criminal justice among people who inject drugs in Ukraine

Aims: To understand how perceived law enforcement policies and practices contribute to the low rates of utilisation of opioid agonist therapies (OAT) like methadone and buprenorphine among people who inject drugs (PWIDs) in Ukraine. Methods: Qualitative data from 25 focus groups (FGs) with 199 opioid-dependent PWIDs in Ukraine examined domains related to lived or learned experiences with OAT, police, arrest, incarceration and criminal activity and were analysed using grounded theory principles. Findings: Most participants were male (66%), in their late 30s, and previously incarcerated (85%), mainly for drug-related activities. When imprisoned, PWIDs perceived themselves as being “addiction-free”. After prison-release, the confluence of police surveillance and societal stress contributed to participants’ drug use relapse, perpetuating a cycle of searching for money and drugs, followed by re-arrest and re-incarceration. Fear of police and arrest both facilitated OAT entry and simultaneously contributed to avoiding OAT since system-level requirements identified OAT clients as targets for police harassment. OAT represents an evidence-based option to “break the cycle”; however, law enforcement practices still thwart OAT capacity to improve individual and public health. Conclusion: In the absence of structural changes in law enforcement policies and practices in Ukraine, PWIDs will continue to avoid OAT and perpetuate the addiction cycle with high imprisonment rates.