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Abstract Background Africa bears a disproportionately high burden of globally significant disease but has lagged in knowledge production to address its health challenges. In this contribution, we discuss the challenges and approaches to health research capacity strengthening in sub-Saharan Africa and propose that the recent shift to an African-led approach is the most optimal. Methods and findings We introduce several capacity building approaches and recent achievements, explore why African-led research on the continent is a potentially paradigm-shifting and innovative approach, and discuss the advantages and challenges thereof. We reflect on the approaches used by the African Academy of Sciences (AAS)-funded Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE) consortium as an example of an effective African-led science and capacity building programme. We recommend the following as crucial components of future efforts: 1. Directly empowering African-based researchers, 2. Offering quality training and career development opportunities to large numbers of junior African scientists and support staff, and 3. Effective information exchange and collaboration. Furthermore, we argue that long-term investment from international donors and increasing funding commitments from African governments and philanthropies will be needed to realise a critical mass of local capacity and to create and sustain world-class research hubs that will be conducive to address Africa’s intractable health challenges. Conclusions Our experiences so far suggest that African-led research has the potential to overcome the vicious cycle of brain-drain and may ultimately lead to improvement of health and science-led economic transformation of Africa into a prosperous continent.

Abstract Background With an increasing number of countries implementing Option B+ guidelines of lifelong antiretroviral therapy (ART) for all pregnant and breastfeeding women, there is urgent need to identify effective approaches for retaining this growing and highly vulnerable population in ART care. Methods Newly postpartum, breastfeeding women who initiated ART in pregnancy and met eligibility criteria were enrolled, and offered the choice of two options for postpartum ART care: (i) referral to existing network of community-based adherence clubs or (ii) referral to local primary health care clinic (PHC). Women were followed at study measurement visits conducted separately from either service. Primary outcome was a composite endpoint of retention in ART services and viral suppression [VS

Therapy for aggressive metastatic breast cancer remains a great challenge for modern biomedicine. Biocompatible polymer nanoparticles have been successfully used in clinic and are seen as a potential solution. Specifically, researchers are exploring the development of chemotherapeutic nanoagents targeting the membrane-associated receptors of cancer cells, such as HER2. However, there are no targeting nanomedications that have been approved for human cancer therapy. Novel strategies are being developed to alter the architecture of agents and optimize their systemic administration. Here, we describe a combination of these approaches, namely, the design of a targeted polymer nanocarrier and a method for its systemic delivery to the tumor site. Namely, PLGA nanocapsules loaded with a diagnostic dye, Nile Blue, and a chemotherapeutic compound, doxorubicin, are used for two-step targeted delivery using the concept of tumor pre-targeting through the barnase/barstar protein “bacterial superglue”. The first pre-targeting component consists of an anti-HER2 scaffold protein, DARPin9_29 fused with barstar, Bs-DARPin9_29, and the second component comprises chemotherapeutic PLGA nanocapsules conjugated to barnase, PLGA-Bn. The efficacy of this system was evaluated in vivo. To this aim, we developed an immunocompetent BALB/c mouse tumor model with a stable expression of human HER2 oncomarkers to test the potential of two-step delivery of oncotheranostic nano-PLGA. In vitro and ex vivo studies confirmed HER2 receptor stable expression in the tumor, making it a feasible tool for HER2-targeted drug evaluation. We demonstrated that two-step delivery was more effective than one-step delivery for both imaging and tumor therapy: two-step delivery had higher imaging capabilities than one-step and a tumor growth inhibition of 94.9% in comparison to 68.4% for the one-step strategy. The barnase*barstar protein pair has been proven to possess excellent biocompatibility, as evidenced by the successful completion of biosafety tests assessing immunogenicity and hemotoxicity. This renders the protein pair a highly versatile tool for pre-targeting tumors with various molecular profiles, thereby enabling the development of personalized medicine.

Summary: Background: Biomarkers correlating with Mycobacterium tuberculosis infection activity/burden in asymptomatic individuals are urgently needed to identify and treat those at highest risk for developing active tuberculosis (TB). Our main objective was to identify plasma host protein biomarkers that change over time prior to developing TB in people living with HIV (PLHIV). Methods: Using multiplex MRM-MS, we investigated host protein expressions from 2 years before until time of TB diagnosis in longitudinally collected (every 3-6 months) and stored plasma from PLHIV with incident TB, identified within a South African (SA) and US cohort. We performed temporal trend and discriminant analyses for proteins, and, to assure clinical relevance, we further compared protein levels at TB diagnosis to interferon-gamma release assay (IGRA; SA) or tuberculin-skin test (TST; US) positive and negative cohort subjects without TB. SA and US exploratory data were analyzed separately. Findings: We identified 15 proteins in the SA (n=30) and 10 in the US (n=24) incident TB subjects which both changed from 2 years prior until time of TB diagnosis after controlling for 10% false discovery rate, and were significantly different at time of TB diagnosis compared to non-TB subjects (p

Targeted nanoparticles of different origins are considered as new-generation diagnostic and therapeutic tools. However, there are no targeted drug formulations within the composition of nanoparticles approved by the FDA for use in the clinic, which is associated with the insufficient effectiveness of the developed candidates, the difficulties of their biotechnological production, and inadequate batch-to-batch reproducibility. Targeted protein self-assembling nanoparticles circumvent this problem since proteins are encoded in DNA and the final protein product is produced in only one possible way. We believe that the combination of the endless biomedical potential of protein carriers as nanoparticles and the standardized protein purification protocols will make significant progress in “magic bullet” creation possible, bringing modern biomedicine to a new level. In this review, we are focused on the currently existing platforms for targeted self-assembling protein nanoparticles based on transferrin, lactoferrin, casein, lumazine synthase, albumin, ferritin, and encapsulin proteins, as well as on proteins from magnetosomes and virus-like particles. The applications of these self-assembling proteins for targeted delivery in vitro and in vivo are thoroughly discussed, including bioimaging applications and different therapeutic approaches, such as chemotherapy, gene delivery, and photodynamic and photothermal therapy. A critical assessment of these protein platforms’ efficacy in biomedicine is provided and possible problems associated with their further development are described.

Three new Pt(II) complexes [(dpp-DAD)PtCl2] (I), [(Mes-DAD(Me)2)PtCl2] (II) and [(dpp-DAD(Me)2)PtCl2] (III) were synthesized by the direct reaction of [(CH3CN)2PtCl2] and corresponding redox-active 1,4-diaza-1,3-butadienes (DAD). The compounds were isolated in a single crystal form and their molecular structures were determined by X-ray diffraction. The purity of the complexes and their stability in solution was confirmed by NMR analysis. The Pt(II) ions in all compounds are in a square planar environment. The electrochemical reduction of complexes I–III proceeds in two successive cathodic stages. The first quasi-reversible reduction leads to the relatively stable monoanionic complexes; the second cathodic stage is irreversible. The coordination of 1,4-diaza-1,3-butadienes ligands with PtCl2 increases the reduction potential and the electron acceptor ability of the DAD ligands. The synthesized compounds were tested in relation to an adenocarcinoma of the ovary (SKOV3).

Nanoparticle-based chemotherapy is considered to be an effective approach to cancer diagnostics and therapy in modern biomedicine. However, efficient tumor targeting remains a great challenge due to the lack of specificity, selectivity, and high dosage of chemotherapeutic drugs required. A two-step targeted drug delivery strategy (DDS), involving cancer cell pre-targeting, first with a first nontoxic module and subsequent targeting with a second complementary toxic module, is a solution for decreasing doses for administration and lowering systemic toxicity. To prove two-step DDS efficiency, we performed a direct comparison of one-step and two-step DDS based on chemotherapy loaded PLGA nanoparticles and barnase*barstar interface. Namely, we developed and thoroughly characterized the two-step targeting strategy of HER2-overexpressing cancer cells. The first targeting block consists of anti-HER2 scaffold polypeptide DARPin9_29 fused with barstar. Barstar exhibits an extremely effective binding to ribonuclease barnase with Kaff = 1014 M−1, thus making the barnase*barstar protein pair one of the strongest known protein*protein complexes. A therapeutic PLGA-based nanocarrier coupled to barnase was used as a second targeting block. The PLGA nanoparticles were loaded with diagnostic dye, Nile Blue, and a chemotherapeutic drug, doxorubicin. We showed that the two-step DDS increases the performance of chemotherapy-loaded nanocarriers: IC50 of doxorubicin delivered via two-step DDS was more than 100 times lower than that for one-step DDS: IC50 = 43 ± 3 nM for two-step DDS vs. IC50 = 4972 ± 1965 nM for one-step DDS. The obtained results demonstrate the significant efficiency of two-step DDS over the classical one-step one. We believe that the obtained data will significantly change the direction of research in developing targeted anti-cancer drugs and promote the creation of new generation cancer treatment strategies.

The extreme aggressiveness and lethality of many cancer types appeal to the problem of the development of new-generation treatment strategies based on smart materials with a mechanism of action that differs from standard treatment approaches. The targeted delivery of nanoparticles to specific cancer cell receptors is believed to be such a strategy; however, there are no targeted nano-drugs that have successfully completed clinical trials to date. To meet the challenge, we designed an alternative way to eliminate tumors in vivo. Here, we show for the first time that the targeting of lectin-equipped polymer nanoparticles to the glycosylation profile of cancer cells, followed by photodynamic therapy (PDT), is a promising strategy for the treatment of aggressive tumors. We synthesized polymer nanoparticles loaded with magnetite and a PDT agent, IR775 dye (mPLGA/IR775). The magnetite incorporation into the PLGA particle structure allows for the quantitative tracking of their accumulation in different organs and the performing of magnetic-assisted delivery, while IR775 makes fluorescent in vivo bioimaging as well as light-induced PDT possible, thus realizing the theranostics concept. To equip PLGA nanoparticles with targeting modality, the particles were conjugated with lectins of different origins, and the flow cytometry screening revealed that the most effective candidate for breast cancer cell labeling is ConA, a lectin from Canavalia ensiformis. In vivo experiments showed that after i.v. administration, mPLGA/IR775–ConA nanoparticles efficiently accumulated in the allograft tumors under the external magnetic field; produced a bright fluorescent signal for in vivo bioimaging; and led to 100% tumor growth inhibition after the single session of PDT, even for large solid tumors of more than 200 mm3 in BALB/c mice. The obtained results indicate that the mPLGA/IR775 nanostructure has great potential to become a highly effective oncotheranostic agent.

No abstract available.

Infectious diseases remain a major health challenge in developing countries, compounding the woes of growing noncommunicable diseases such as chronic kidney disease (CKD). Increased morbidity and mortality have been reported among CKD patients with hepatitis infection and may necessitate protocol for treatment, follow-up, and prevention of spread. We aimed to determine the prevalence of viral hepatitis B and C infections among CKD patients and the effects on their liver enzymes. In this retrospective study, 314 CKD patients screened for hepatitis C virus (HCV) and hepatitis B surface antigen (HBsAg) were reviewed. Participants were screened at the time of diagnosis of CKD or referral, using qualitative enzyme immunoassay rapid test kits before the initiation of treatment. Individuals who were reactive to human immunodeficiency virus were excluded, and data were analyzed using IBM SPSS Statistics version 21.0. Participants included 206 males (65.6%) and 108 females (34.4%), with a mean age of 50.5 ± 16.3 years. The seroprevalence of HBsAg, HCV, and coinfection was seen in 15.6% (49), 4.8% (15), and 0.92% of the patients, respectively. More than half (63.6%) of the seropositive patients were below 50 years of age. Alanine transaminase (ALT) activity was higher in HCV seropositive than negative (10.5 ± 10.5 vs. 21.2 ± 35.9) (P = 0.001), while aspartate transaminase (AST) and alkaline phosphatase (ALP) were similar. ALT, AST, and ALP were also similar between HBsAg-seropositive and HBsAg-negative patients. The prevalence of hepatitis B and C is high among our CKD patients. This suggests the need for improved screening and treatment of hepatitis infection in this group. Immunization may also be essential to prevent its spread among patients requiring hemodialysis.

Introduction: The retinoprotective effect of the 11-amino acid fragment of darbepoetin PRK-002 on the models of hypertensive retinal angiopathy and hypertensive neuroretinopathy in Wistar rats was investigated in comparison with carbamylated darbepoetin and sulodexide. Materials and methods: The protective effects of the pharmacological agents were assessed using the following criteria: a semi-quantitative assessment of changes in the eye fundus when performing ophthalmoscopy, the retinal blood flow, the b/a coefficient, eNOs expression in retinal vessels, specific number of neuronal nuclei in the inner nuclear layer, and p53 expression in the retina. Results and discussion: A pronounced protective effect, exceeding sulodexide at a dose of 150 LRU/kg and carbamylated darbepoetin at a dose of 300 μg/kg when correcting retinal angiopathy was observed in PRK-002 at a dose of 4 µg/kg, which expressed in adjustment of the retinal vessels’ calibers, removing retinal arterio-venous crossings, reaching the target levels of the retinal microcirculation, the b/a coefficient, and the restoration of eNOs expression in the endothelium of retinal vessels. PRK-002 at a dose of 4 µg/kg has a pronounced neuroprotective effect comparable to carbamylated darbepoetin at a dose of 300 µg/kg in correction of hypertensive neuroretinopathy, which expressed in the normalization of the fundus image, reaching the b/a target values, the specific number of neuronal nuclei in the inner nuclear layer, inhibition of p53 expression in the neurons of the inner nuclear and ganglionic layers. Conclusion: The study revealed angio- and neuroprotective activity of the 11-amino acid fragment of darbepoetin PRK-002 in correction of retinal injury formed on the background of hypertension.

The overly reliance on getting ‘tough on drugs policy’ by the Nigerian government is counterproductive, as the problem is still on the increase. This has called for explicit and formal incorporation of social marketing strategies into our legal framework for better outcomes in the ‘war on drugs’. Theory deconstruction (i.e. integrated model approach) was adopted to underpin the perspectives raised on the utility of social marketing as a noncustodial drug-use prevention and control mechanism. Findings revealed that the programme discourages drug-use behaviours through media education, counselling, and advertorial sea change in decision-making processes and drives. Both potential and actual users are sensitised to the dangers of drugs and how to desist (for users) and resist (for potential users) the temptation and contemplation to experiment with drugs. The issues raised suggested policy direction which orientated the conclusion, policy implications and suggestions for further studies. Commonly abused by the youth population, alcohol, marijuana, tobacco, and new/emerging local psychoactive substances, were found to be effectively curtailed using this approach. The promise of social marketing in combating youth drug culture is phenomenal and yet the framework is only tangentially discussed and referenced in most drug discourses. There is urgent need and necessity to incorporate the idea into our educational curricula and national drug plans. It is also suggested that additional studies be conducted on the subject matter using a more sophisticated scientific tools to further measure the strengths of social marketing variables in combating illicit substance use.

Metal hydride systems for hydrogen storage are now commercially manufactured and the demand for them is constantly growing. Metal hydrides have the following features: a unique combination of properties of metal-hydrogen systems; extremely high volumetric densities of hydrogen atoms in the metal matrix; a wide range of operating pressures and temperatures; the selectivity of the hydrogen absorption process; significant changes in the physical properties of the metal when it is saturated with hydrogen; their catalytic activity, etc. The purpose of our research was to study the effect of the temperature of cathodic polarisation on the diffusion-kinetic, thermodynamic, and physical properties of Al-Sm-H alloys. In our study we used electrodes of Al-Sm-H alloys obtained electrochemically using cathodic intercalation from a 0.5 M dimethylformamide solution of samarium salicylate at Еcp = –2.9 V (relative to the non-aqueous silver chloride electrode) and the temperature of 25 °С for 1 hour. We used the electromotive force method to determine the thermodynamic properties: Gibbs free energy (ΔG), entropy (ΔS), and enthalpy (ΔH). The potentiostatic method was used to calculate the diffusionkinetic properties: intercalation constants, adsorption, switching current density, and the diffusion coefficient. The microstructural analysis allowed us to determine the effect of the temperature on the changes in the surface morphology. The study showed that an increase in the temperature results in an increase in ΔG, ΔS, and ΔH, which means that at higher temperatures the degree of the system disorder increases. Nevertheless, the calculated characteristics comply with the existing literature.

Background: Uncorrected presbyopia and its impact on the quality of life was performed as part of a community research towards strengthening the provision of optical services for Sagamu Local Government Area of Ogun State, Nigeria. Aim: To determine the effect of uncorrected presbyopia on the quality of life of adults of 30 years old and above in Sagamu, Southwest, Nigeria. Setting: This study consisted of the permanent resident adults of the town and village settlements within the local government. Methods: Examination of respondents included distance visual acuity measurement with or without pinhole at 6 metres using the Snellen’s chart. Near assessment was performed at 40 centimetres with the distance correction in place if required. The semi-structured questionnaire which contained demographics and near-vision task difficulties, et cetera, was administered. Ethical approval was obtained. The data were entered and analysed using Statistical Package for Social Sciences version 16 statistical software. Results: The study showed that presbyopes significantly reported not being satisfied with near-vision (p = 0.0001) and requiring help because of near-vision problems (p = 0.0004) more than non-presbyopes. The most difficult presbyopic activities were reading, writing, sorting grains, threading needle, cutting fingernails and recognising small objects. All were statistically significant (each with p ≤ 0.0001). Conclusion: The impact of reduced near vision on the quality of life in Sagamu, Nigeria, is striking and similar to findings around the world. So, any optical services plan for the local government area has to include presbyopic corrections.

Extracellular vesicles (EVs) are promising agents for liquid biopsy—a non-invasive approach for the diagnosis of cancer and evaluation of therapy response. However, EV potential is limited by the lack of sufficiently sensitive, time-, and cost-efficient methods for their registration. This research aimed at developing a highly sensitive and easy-to-use immunochromatographic tool based on magnetic nanoparticles for EV quantification. The tool is demonstrated by detection of EVs isolated from cell culture supernatants and various body fluids using characteristic biomarkers, CD9 and CD81, and a tumor-associated marker—epithelial cell adhesion molecules. The detection limit of 3.7 × 105 EV/µL is one to two orders better than the most sensitive traditional lateral flow system and commercial ELISA kits. The detection specificity is ensured by an isotype control line on the test strip. The tool’s advantages are due to the spatial quantification of EV-bound magnetic nanolabels within the strip volume by an original electronic technique. The inexpensive tool, promising for liquid biopsy in daily clinical routines, can be extended to other relevant biomarkers.

Nanoparticles exhibiting the localized surface plasmon resonance (LSPR) phenomenon are promising tools for diagnostics and cancer treatment. Among widely used metal nanoparticles, silver nanoparticles (Ag NPs) possess the strongest light scattering and surface plasmon strength. However, the therapeutic potential of Ag NPs has until now been underestimated. Here we show targeted photothermal therapy of solid tumors with 35 nm HER2-targeted Ag NPs, which were produced by the green synthesis using an aqueous extract of Lavandula angustifolia Mill. Light irradiation tests demonstrated effective hyperthermic properties of these NPs, namely heating by 10 °C in 10 min. To mediate targeted cancer therapy, Ag NPs were conjugated to the scaffold polypeptide, affibody ZHER2:342, which recognizes a clinically relevant oncomarker HER2. The conjugation was mediated by the PEG linker to obtain Ag-PEG-HER2 nanoparticles. Flow cytometry tests showed that Ag-PEG-HER2 particles successfully bind to HER2-overexpressing cells with a specificity comparable to that of full-size anti-HER2 IgGs. A confocal microscopy study showed efficient internalization of Ag-PEG-HER2 into cells in less than 2 h of incubation. Cytotoxicity assays demonstrated effective cell death upon exposure to Ag-PEG-HER2 and irradiation, caused by the production of reactive oxygen species. Xenograft tumor therapy with Ag-PEG-HER2 particles in vivo resulted in full primary tumor regression and the prevention of metastatic spread. Thus, for the first time, we have shown that HER2-directed plasmonic Ag nanoparticles are effective sensitizers for targeted photothermal oncotherapy.

Assessing knowledge, attitudes, and risk perception of Nigerian broiler grow-out farmers (n = 152) to antimicrobial resistance (AMR) with a five sectional purposive-structured-questionnaire: demographics; knowledge; attitudes; risk-perception; and response to regulation of antimicrobial practices. Data were analyzed using descriptive statistics, chi-square test, and binary logistic regression. Respondents’ knowledge score, in total, was lower than average, with all (100%) respondents having the understanding that antibiotics kill/reduce bacteria, most participants (>73%) believing that feeding antibiotics to broiler chickens is a necessity for weight gain, and many (>69%) thinking that no negative side-effects exist with the use of antibiotics. Poor attitude towards antimicrobial usage was prevalent (>63%) with unsatisfactory performance in most instruments: >60% of farmers reported using antimicrobials every week and still use antimicrobials when birds appear sick, and most (>84%) arbitrarily increase the drug dosages when used. However, a satisfactory performance score was reported (68%) in risk perception of AMR with >63% perceiving that inappropriate use of antibiotics is the main factor causing the emergence of resistant bacteria; >65.8% expressed that AMR in broiler chickens is not essential for public health, that AMR cannot develop from broiler bacteria diseases, that increasing the frequency of antimicrobial use cannot increase AMR in future, and that usage cannot lead to antibiotic residue in broiler-meat products leading to AMR development in human. None of the respondents were aware of any regulation for monitoring antimicrobial use. Significant factors associated with knowledge, attitudes, and risk perception of antimicrobial use and resistance among broiler grow-out farmers include marital status, farm category, education, educational specialization, sales target, growth duration/cycle, broiler stocking batch, and feed source. Identified gaps exist in AMR awareness among Nigerian broiler farmers and should be targeted through stakeholders’ participation in combatting AMR threats.

Mms6 is a protein that plays crucial role in the biomineralization and formation of magnetosomes in magnetotactic bacteria Magnetospirillum magneticum (strain AMB-1). We developed a fusion protein of C-term part of Mms6 and Barstar (natural inhibitor of ribonuclease Barnase), namely, Bs-C-Mms6. This protein successfully stabilized uncoated monocrystalline Fe3O4 magnetite nanoparticles in buffered solutions. Here, we present data regarding the synthesis and characterization of magnetite nanoparticles stabilized with Bs-C-Mms6. For further interpretation of the data presented in this article, please see the research article ‘Self-assembling nanoparticles biofunctionalized with magnetite-binding protein for the targeted delivery to HER2/neu overexpressing cancer cells’ (Shipunova et al., 2018) [1].

Abstract The Hardy–Rogers p-proximal cyclic contraction, which includes the cyclic, Kannan, Chatterjea and Reich contractions as sub-classes, is developed in uniform spaces. The existence and uniqueness results of best proximity points for these contractions are proved. The results, which are for non-self maps, apart from the fact that they are new in literature, generalise several other similar results in literature. Examples are given to validate the results obtained.

Abstract Background The rollout of universal, lifelong treatment for all HIV-positive pregnant and breastfeeding women (“Option B+”) has rapidly increased the number of women initiating antiretroviral treatment (ART) and requiring ART care postpartum. In a pilot project in South Africa, eligible postpartum women were offered the choice of referral to the standard of care, a local primary health care clinic, or a community-based model of differentiated ART services, the adherence club (AC). ACs have typically enrolled only non-pregnant and non-postpartum adults; postpartum women had not previously been referred directly from antenatal care. There is little evidence regarding postpartum women’s preferences for and experiences of differentiated models of care, or the capacity of this particular model to cater to their specific needs. This qualitative paper reports on feedback from both postpartum women and health workers who care for them on their respective experiences of the AC. Methods One-on-one in-depth qualitative interviews were conducted with 19 (23%) of the 84 postpartum women who selected the AC and were retained at approximately 12 months postpartum, and 9 health workers who staff the AC. Data were transcribed and thematically analysed using NVivo 11. Results Postpartum women’s inclusion in the AC was acceptable for both participants and health workers. Health workers were welcoming of postpartum women but expressed concerns about prospects for longer term adherence and retention, and raised logistical issues they felt might compromise trust with AC members in general. Conclusions Enrolling postpartum women in mixed groups with the general adult population is feasible and acceptable. Preliminary recommendations are offered and may assist in supporting the specific needs of postpartum women transitioning from antenatal ART care. Trial registration Number NCT02417675 clinicaltrials.gov/ct2/show/record/NCT02417675 (retrospective reg.)

The development of non-invasive photothermal therapy (PTT) methods utilizing nanoparticles as sensitizers is one of the most promising directions in modern oncology. Nanoparticles loaded with photothermal dyes are capable of delivering a sufficient amount of a therapeutic substance and releasing it with the desired kinetics in vivo. However, the effectiveness of oncotherapy methods, including PTT, is often limited due to poor penetration of sensitizers into the tumor, especially into solid tumors of epithelial origin characterized by tight cellular junctions. In this work, we synthesized 200 nm nanoparticles from the biocompatible copolymer of lactic and glycolic acid, PLGA, loaded with magnesium phthalocyanine, PLGA/Pht-Mg. The PLGA/Pht-Mg particles under the irradiation with NIR light (808 nm), heat the surrounding solution by 40 °C. The effectiveness of using such particles for cancer cells elimination was demonstrated in 2D culture in vitro and in our original 3D model with multicellular spheroids possessing tight cell contacts. It was shown that the mean inhibitory concentration of such nanoparticles upon light irradiation for 15 min worsens by more than an order of magnitude: IC50 increases from 3 µg/mL for 2D culture vs. 117 µg/mL for 3D culture. However, when using the JO-4 intercellular junction opener protein, which causes a short epithelial–mesenchymal transition and transiently opens intercellular junctions in epithelial cells, the efficiency of nanoparticles in 3D culture was comparable or even outperforming that for 2D (IC50 = 1.9 µg/mL with JO-4). Synergy in the co-administration of PTT nanosensitizers and JO-4 protein was found to retain in vivo using orthotopic tumors of BALB/c mice: we demonstrated that the efficiency in the delivery of such nanoparticles to the tumor is 2.5 times increased when PLGA/Pht-Mg nanoparticles are administered together with JO-4. Thus the targeting the tumor cell junctions can significantly increase the performance of PTT nanosensitizers.

Biopolymers, in particular collagen and fibrinogen, are the leading materials for use in tissue engineering. When developing technology for scaffold formation, it is important to understand the properties of the source materials as well as the mechanisms that determine the formation of the scaffold structures. Both factors influence the properties of scaffolds to a great extent. Our present work aimed to identify the features of the molecular characteristics of collagens of different species origin and the changes they undergo during the enzymatic hydrolysis used for the process of scaffold formation. For this study, we used the methods of gel-penetrating chromatography, dynamic light scattering, reading IR spectra, and scanning electron microscopy. It was found that cod collagen (CC) and bovine collagen (BC) have different initial molecular weight parameters, and that, during hydrolysis, the majority of either type of protein is hydrolyzed by the proteolytic enzymes within the first minute. The differently sourced collagen samples were also hydrolyzed with the formation of two low molecular fractions: Mw ~ 10 kDa and ~20 kDa. In the case of CC, the microstructure of the final scaffolds contained denser, closely spaced fibrillar areas, while the BC-sourced scaffolds had narrow, short fibrils composed of unbound fibers of hydrolyzed collagen in their structure.

Active implementation of the education controlling systems into the educational process stipulates the realization of automatic control of the level of students’ training. In such circumstances, there arises an opportunity to explore integrated means which can be used to evaluate the quality of testing materials. An overview of embedded functions of the Moodle system for test analysis according to statistical characteristics is presented in the article. Empirical studies of the test on a representative sample of test takers help to evaluate the informativity of tasks. The test is formed by such a system of tasks which provides informative assessment of the level and quality of students’ training. Characteristics of the test as a means of pedagogical measuring show the dependence of informational content of the test on the characteristics of test tasks and on the level of students’ training. The work with the "Statistics" module is considered in detail. Pedagogical potential of built-in LMS Moodle services and their use in the educational measurement theory is shown.

Background: The use of plants and plant products for medicinal purposes is an age-long practice in traditional communities and is becoming prominent globally. This study was performed to evaluate the effect of ethanolic extract of Chromolaena odorata on the kidney and intestine of albino rats. Methods: Twenty growing albino rats with an average weight of 54 g were used in this study. They were grouped into four groups. Groups 1, 2, and 3, known as the test groups, were given 50 mg/kg, 100 mg/kg, and 250 mg/kg ethanolic extract of C. odorata, respectively, while the control group was given distilled water orally. The experiment was performed for 6 weeks. The animals were killed using chloroform suffocation. The kidneys and the intestine were harvested and fixed in 10% neutral buffered formalin for histological analysis. Blood samples were collected from the animals by heart puncture for estimation of creatinine and urea levels. Results: The creatinine, urea, aspartate aminotransferase, alanine transaminase, and alkaline phosphatase levels of blood sample from the test group were significantly different when compared with the control (p

Libraries are very important for information, communication and transformation. They help to inculcate a reading culture for an upward progression of people’s life. They reduce ignorance, thus they are empowering literacy, knowledge and skill acquisition. This paper is an opinion paper. The authors employed literature research methodology to carry out the analysis. It gives an insight into the reading culture of different nations and further portrays the role of libraries in promoting reading and an effective reading environment in the society. The authors also aim at improving the reading culture of different nations by using their own nation as a case study. The paper demonstrates that establishing of reading clubs, reviving of education in the schools through electronic libraries, promotion of books and reading in the media are those factors that could improve the situation of reading.

Characterizing the fitness landscape, a representation of fitness for a large set of genotypes, is key to understanding how genetic information is interpreted to create functional organisms. Here we determined the evolutionarily-relevant segment of the fitness landscape of His3, a gene coding for an enzyme in the histidine synthesis pathway, focusing on combinations of amino acid states found at orthologous sites of extant species. Just 15% of amino acids found in yeast His3 orthologues were always neutral while the impact on fitness of the remaining 85% depended on the genetic background. Furthermore, at 67% of sites, amino acid replacements were under sign epistasis, having both strongly positive and negative effect in different genetic backgrounds. 46% of sites were under reciprocal sign epistasis. The fitness impact of amino acid replacements was influenced by only a few genetic backgrounds but involved interaction of multiple sites, shaping a rugged fitness landscape in which many of the shortest paths between highly fit genotypes are inaccessible.

The relevance of the topics investigated due to acute socioeconomic problems of extinction of Russian villages. Desertification is in the process of disappearance ten thousand villages, which continues its devastating pace. The article addressed the issue of the revival of Russian villages, construction, and upgrading of rural settlements based on the realization of the Federal program "sustainable development of rural territories in the years 2014-2017 and for the period up to 2020". Revival and construction of rural settlements today mainly involves the development of agricultural holdings on the basis of which will be established equipped agricultural town. Any country associated with a particular way of perceiving not only significant monuments of its culture and architecture but also the types of rural settlements. The village is not a business project; and thelifestyle of a Russian man, a certain way of all cultural, social and economic relations. Currently, the increase of rural settlements and revitalizing rurallife is happening on several fronts: a) building settlements with agro holdings; b) farms; c) creating few ecovillage; d) Renaissance village through the townspeople-truckers as a new phenomenon. Types of rural settlements in Russia are very diverse. They are, first and foremost, thelandscape of the countryside, the direction of agricultural production, ethnic features. In residential areas with recreational and cultural potentials, farms should be promoted and personal subsidiary farms, which will focus on quality and a variety of agricultural products. The revival of villages and rural areas concerned, first and foremost, the provincial small farmsteads landlords "high hand", little knownlocations of handicrafts. It is proposed to simplify thelegislation documents for the category of "noteworthy" in relation to the territories of rural settlements with historical and cultural potential.

Overwhelming empirical evidence has highlighted the contribution of indiscriminate antibiotic usage (ABU) in food animals to the overall burden of antibiotic resistance (ABR) in humans, thus making antibiotic use the main selective pressure driving antibiotic resistance. The social and behavioral perspective on antibiotic use and resistance in poultry is limited. Our study therefore aimed at obtaining information on antibiotic usage, awareness of ABR, and the attitude and perceptions towards prudent antibiotic usage and ABR. A cross-sectional survey using a structured questionnaire was conducted in 125 poultry farms in Kwara state in December 2019. Most farmers (69.6%, n = 87/125) were aware of ABR and had satisfactory knowledge about ABR with a mean knowledge score of 3.2 ± 1.5. Age (older farmers; OR: 1.1, 95% CI: 1.0, 1.2) and gender (male respondents, OR: 8.5, 95% CI: 3.0, 23.9; p < 0.01) were more likely to have satisfactory knowledge of ABR. Tertiary education was significantly associated with ABR awareness (OR: 4.7; 95% CI: 0.1, 0.7; p = 0.007) and the ABR knowledge level (OR: 7.8; 95% CI: 3.3, 18.7; p < 0.01). Higher flock size was significantly associated with a satisfactory knowledge of ABR (OR: 9.5; 95% CI: 3.8, 23.6; p < 0.01). Most of the poultry farmers (68%) had positive attitudes towards prudent antibiotic use with a mean score of 2.7 ± 0.9. On the contrary, only 32.8% of poultry farmers had a desirable perception of ABR with a mean perception score of 4.9 ± 1.1. The ABR knowledge level was significantly associated with the perceptions of farmers (p < 0.05) but not their attitudes toward ABU and ABR (p = 0.083). There was evidence of unprescribed use of antibiotics in poultry and a failure to observe antibiotic withdrawal periods. These constitute a risk of exposure to unacceptable levels of drug residues from poultry products and an increased risk of ABR. Improving education and communication on antibiotic stewardship programs are crucial to prevent the looming antibiotic threat.

Hyperthermia has been used as an adjuvant treatment for radio- and chemotherapy for decades. In addition to its effects on perfusion and oxygenation of cancer tissues, hyperthermia can enhance the efficacy of DNA-damaging treatments such as radiotherapy and chemotherapy. Although it is believed that the adjuvant effects are based on hyperthermia-induced dysfunction of DNA repair systems, the mechanisms of these dysfunctions remain elusive. Here, we propose that elevated temperatures can induce chromatin trapping (c-trapping) of essential factors, particularly those involved in DNA repair, and thus enhance the sensitization of cancer cells to DNA-damaging therapeutics. Using mass spectrometry-based proteomics, we identified proteins that could potentially undergo c-trapping in response to hyperthermia. Functional analyses of several identified factors involved in DNA repair demonstrated that c-trapping could indeed be a mechanism of hyperthermia-induced transient deficiency of DNA repair systems. Based on our proteomics data, we showed for the first time that hyperthermia could inhibit maturation of Okazaki fragments and activate a corresponding poly(ADP-ribose) polymerase-dependent DNA damage response. Together, our data suggest that chromatin trapping of factors involved in DNA repair and replication contributes to heat-induced radio- and chemosensitization.

There is a growing awareness that pregnancy can set the foundations for an array of diverse medical conditions in the offspring, including obesity. A wide assortment of factors, including genetic, epigenetic, lifestyle, and diet can influence foetal outcomes. This article reviews the role of melatonin in the prenatal modulation of offspring obesity. A growing number of studies show that many prenatal risk factors for poor foetal metabolic outcomes, including gestational diabetes and night-shift work, are associated with a decrease in pineal gland-derived melatonin and associated alterations in the circadian rhythm. An important aspect of circadian melatonin’s effects is mediated via the circadian gene, BMAL1, including in the regulation of mitochondrial metabolism and the mitochondrial melatoninergic pathway. Alterations in the regulation of mitochondrial metabolic shifts between glycolysis and oxidative phosphorylation in immune and glia cells seem crucial to a host of human medical conditions, including in the development of obesity and the association of obesity with the risk of other medical conditions. The gut microbiome is another important hub in the pathoetiology and pathophysiology of many medical conditions, with negative consequences mediated by a decrease in the short-chain fatty acid, butyrate. The effects of butyrate are partly mediated via an increase in the melatoninergic pathway, indicating interactions of the gut microbiome with melatonin. Some of the effects of melatonin seem mediated via the alpha 7 nicotinic receptor, whilst both melatonin and butyrate may regulate obesity through the opioidergic system. Oxytocin, a recently recognized inhibitor of obesity, may also be acting via the opioidergic system. The early developmental regulation of these processes and factors by melatonin are crucial to the development of obesity and many diverse comorbidities.

Enzymatic hydrolysis of native collagen and fibrinogen was carried out under comparable conditions at room temperature. The molecular weight parameters of proteins before and after hydrolysis by thrombin were monitored by gel-penetrating chromatography (GPC). An analysis of the experiment results shows that the molecular weight parameters of the initial fibrinogen (Fn) and cod collagen (CC) are very similar. High molecular CC decays within the first minute, forming two low molecular fractions. The main part (~80%) falls on the fraction with a value of Mw less than 10 kDa. The initial high molecular fraction of Fn with Mw ~320–340 kDa is not completely hydrolyzed even after three days of control. The presence of low molecular fractions with Mw ~17 and Mw ~10 kDa in the solution slightly increases within an hour and noticeably increases for three days. The destruction of macromolecules of high molecular collagen to hydrolysis products appears almost completely within the first minute mainly to the polymer with Mw ~10 kDa, and enzymatic hydrolysis of fibrinogen proceeds slower than that of collagen, but also mainly to the polymer with Mw ~10 kDa. Comparative photos of the surfaces of native collagen, fibrinogen and the scaffold based on them were obtained.

Structural and functional alterations of mitochondria are intimately linked to a wide array of medical conditions. Many factors are involved in the regulation of mitochondrial function, including cytokines, chaperones, chemokines, neurosteroids, and ubiquitins. The role of diffusely located cells of the neuroendocrine system, including biogenic amines and peptide hormones, in the management of mitochondrial function, as well as the role of altered mitochondrial function in the regulation of these cells and system, is an area of intense investigation. The current article looks at the interactions among the cells of the neuronal-glia, immune and endocrine systems, namely the diffuse neuroimmunoendocrine system (DNIES), and how DNIES interacts with mitochondrial function. Whilst changes in DNIES can impact on mitochondrial function, local, and systemic alterations in mitochondrial function can alter the component systems of DNIES and their interactions. This has etiological, course, and treatment implications for a wide range of medical conditions, including neurodegenerative disorders. Available data on the role of melatonin in these interactions, at cellular and system levels, are reviewed, with directions for future research indicated.

Biomarkers for active tuberculosis (TB) are urgently needed to improve rapid TB diagnosis. The objective of this study was to identify serum protein expression changes associated with TB but not latent Mycobacterium tuberculosis infection (LTBI), uninfected states, or respiratory diseases other than TB (ORD). Serum samples from 209 HIV uninfected (HIV−) and co-infected (HIV+) individuals were studied. In the discovery phase samples were analyzed via liquid chromatography and mass spectrometry, and in the verification phase biologically independent samples were analyzed via a multiplex multiple reaction monitoring mass spectrometry (MRM-MS) assay. Compared to LTBI and ORD, host proteins were significantly differentially expressed in TB, and involved in the immune response, tissue repair, and lipid metabolism. Biomarker panels whose composition differed according to HIV status, and consisted of 8 host proteins in HIV− individuals (CD14, SEPP1, SELL, TNXB, LUM, PEPD, QSOX1, COMP, APOC1), or 10 host proteins in HIV+ individuals (CD14, SEPP1, PGLYRP2, PFN1, VASN, CPN2, TAGLN2, IGFBP6), respectively, distinguished TB from ORD with excellent accuracy (AUC = 0.96 for HIV− TB, 0.95 for HIV+ TB). These results warrant validation in larger studies but provide promise that host protein biomarkers could be the basis for a rapid, blood-based test for TB.

In recent years, chronic immune activation and systemic inflammation have emerged as hallmarks of HIV disease progression and mortality. Several studies indicate that soluble inflammatory biomarkers (sCD14, IL-6, IL-8, CRP and hyaluronic acid), as well as surface markers of T-cell activation (CD38, HLA-DR) independently predict progression to AIDS and mortality in HIV-infected individuals. While co-infections have been shown to contribute to immune activation, the impact of latent tuberculosis infection (LTBI), which is widely endemic in the areas most affected by the global AIDS epidemic, has not been evaluated. We hypothesized that both active and latent states of Mycobacterium tuberculosis co-infection contribute to elevated immune activation as measured by these markers. In HIV-infected individuals with active, but not latent TB, we found elevated levels of soluble markers associated with monocyte activation. Interestingly, T-cell activation was elevated individuals with both latent and active TB. These results suggest that in the highly TB- and HIV-endemic settings of southern Africa, latent TB-associated T-cell activation may contribute to HIV disease progression and exacerbate the HIV epidemic. In addition, our findings indicate that aggressive campaigns to treat LTBI in HIV-infected individuals in high-burden countries will not only impact TB rates, but may also slow HIV progression. Significance: Latent tuberculosis, which affects an estimated 1/3 of the world's population, has long been thought to be a relatively benign, quiescent state of M. tuberculosis infection. While HIV co-infection is known to exacerbate M. tuberculosis infection and increase the risk of developing active TB, little is known about the potential effect of latent TB infection on HIV disease. This study shows that HIV-infected individuals with both active and latent TB have elevated levels of inflammation and immune activation, biomarkers of HIV disease progression and elevated risk of mortality. These results suggest that, in the context of HIV, latent TB infection may be associated with increased risk of progression to AIDS and mortality.

The negotiators, representatives of the Council of Europe member states and of the European Union, fi nalised the draft accession agreement of the European Union to the European Convention on Human Rights in spring, 2013. Due to the fact that the possibility of the accession is now not confi ned to the provisions of Protocol 14 to the European Convention on Human Rights and article 6 of the Treaty on European Union, the questions of cooperation between the ECJ and the ECtHR and interpretation and application of the main European acts on human rights - the European Union Charter of Fundamental Rights and the European Convention on Human Rights - are becoming more and more important.

A 58-year-old female without cardiovascular risk factors, was going to be operated to repair the rotator cuff. Induction and interscalene brachial plexus block were uneventful, but after her placement for surgery the patient started with severe bronchospasm, hypotension, cutaneous allergic reaction and ST elevation on the electrocardiogram. An anaphylactic shock was suspected and treated but until the perfusion of nitroglycerina was started no electrocardiographic changes resolved. After necessary diagnostic test the final diagnosis was variant I of Kounis syndrome due to cefazolin and rocuronium. Ephinephrine is the cornerstone of treatment for anaphylaxis but should we use it if the anaphylactic reaction is also accompanied by myocardial ischemia? The answer is that we should not use it because myocardial ischemia in this syndrome is caused by vasospasm, so it would be more useful drugs such as nitroglycerin. But what if we do not know if it is a Kounis syndrome or not? In this article we report our experience that maybe could help you in a similar situation.

This study investigates stakeholder opinions of the major benefits and barriers of Environmental Management Systems (EMS) to the Nigerian construction industry, and the perceived issues to EMS adoption among organisations in the industry. The study highlights the environment as an important stakeholder in the industry because it affects and is affected by construction activities on a regular basis. It identifies the importance of ISO 14001 in ensuring adequate consideration for the environment is maintained on construction projects. The research adopts a quantitative approach by analysing responses from an online survey among construction industry professionals in Nigeria. The questions on the survey were drawn from a similar study carried out in Asia and the results were analysed using the Weighted Average and Standard Deviation statistical approach. Results reveal that the major benefits of EMS to the Nigerian construction industry were improved efficiency in waste management and environmental protection, as well as an overall increase in employee motivation due to better opportunities for training and development. Lack of technological support in organisations and the high cost of implementing EMS were viewed as the major barriers towards its uptake in construction companies. The findings also indicate that a feasible EMS implementation strategy must not ignore the unique nature of the Nigerian construction industry, which comprises mostly small and medium enterprises. The study concludes by recommending the use of a waste management plan based on the Reuse-reducerecycle-Recover model and an employee training plan to ensure continuous improvement in the organisation’s environmental management strategy.

The ability of antigen-specific T cells to simultaneously produce multiple cytokines is thought to correlate with the functional capacity and efficacy of T cells. These 'polyfunctional' T cells have been associated with control of HIV. We aimed to assess the impact of co-infection with Mycobacterium tuberculosis (MTB) on HIV-specific CD8+ and CD4+ T cell function. We assessed T cell functionality in 34 South African adults by investigating the IFN-y, IL-2, TNF-α, IL-21 and IL-17 cytokine secretion capacity, using polychromatic flow cytometry, following HIV Gag-specific stimulation of peripheral blood mononuclear cells. We show that MTB is associated with lower HIV-specific T cell function in co-infected as compared to HIV mono-infected individuals. This decline in function was greatest in co-infection with active Tuberculosis (TB) compared to co-infection with latent MTB (LTBI), suggesting that mycobacterial load may contribute to this loss of function. The described impact of MTB on HIV-specific T cell function may be a mechanism for increased HIV disease progression in co-infected subjects as functionally impaired T cells may be less able to control HIV.

This classroom note shares experience of using spreadsheets with a group of 2nd grade students. The main feature of the learning environments that made effective the integration of technology and grade appropriate mathematics is the use of images of modern tools such as the Nintendo DC, the Play Station Portable, and the iPhone. The idea is illustrated by presenting a number of worksheets of so modified spreadsheets called integrated spreadsheets. The authors suggest using spreadsheets in that way offers an attractive interface for young students and enhances significantly their on-task behavior.

High expression of CD161 on CD8+ T cells is associated with a population of cells thought to play a role in mucosal immunity. We wished to investigate this subset in an HIV and Mycobacterium tuberculosis (MTB) endemic African setting.A flow cytometric approach was used to assess the frequency and phenotype of CD161++CD8+ T cells. 80 individuals were recruited for cross-sectional analysis: controls (n = 18), latent MTB infection (LTBI) only (n = 16), pulmonary tuberculosis (TB) only (n = 8), HIV only (n = 13), HIV and LTBI co-infection (n = 15) and HIV and TB co-infection (n = 10). The impact of acute HIV infection was assessed in 5 individuals recruited within 3 weeks of infection. The frequency of CD161++CD8+ T cells was assessed prior to and during antiretroviral therapy (ART) in 14 HIV-positive patients.CD161++CD8+ T cells expressed high levels of the HIV co-receptor CCR5, the tissue-homing marker CCR6, and the Mucosal-Associated Invariant T (MAIT) cell TCR Vα7.2. Acute and chronic HIV were associated with lower frequencies of CD161++CD8+ T cells, which did not correlate with CD4 count or HIV viral load. ART was not associated with an increase in CD161++CD8+ T cell frequency. There was a trend towards lower levels of CD161++CD8+ T cells in HIV-negative individuals with active and latent TB. In those co-infected with HIV and TB, CD161++CD8+ T cells were found at low levels similar to those seen in HIV mono-infection.The frequencies and phenotype of CD161++CD8+ T cells in this South African cohort are comparable to those published in European and US cohorts. Low-levels of this population were associated with acute and chronic HIV infection. Lower levels of the tissue-trophic CD161++ CD8+ T cell population may contribute to weakened mucosal immune defense, making HIV-infected subjects more susceptible to pulmonary and gastrointestinal infections and detrimentally impacting on host defense against TB.

Monitoring of latent Mycobacterium tuberculosis infection may prevent disease. We tested an ESAT-6 and CFP-10-specific IFN-γ Elispot assay (RD1-Elispot) on 163 HIV-infected individuals living in a TB-endemic setting. An RD1-Elispot was performed every 3 months for a period of 3-21 months. 62% of RD1-Elispot negative individuals were positive by cultured Elispot. Fluctuations in T cell response were observed with rates of change ranging from -150 to +153 spot-forming cells (SFC)/200,000 PBMC in a 3-month period. To validate these responses we used an RD1-specific real time quantitative PCR assay for monokine-induced by IFN-γ (MIG) and IFN-γ inducible protein-10 (IP10) (MIG: r=0.6527, p=0.0114; IP-10: r=0.6967, p=0.0056; IP-10+MIG: r=0.7055, p=0.0048). During follow-up 30 individuals were placed on ARVs and 4 progressed to active TB. Fluctuations in SFC did not correlate with CD4 count, viral load, treatment initiation, or progression to active TB. The RD1-Elispot appears to have limited value in this setting.

Glioblastoma (GBM) is characterized by exceptionally high intratumoral heterogeneity. However, the molecular mechanisms underlying the origin of different GBM cell populations remain unclear. Here, we found that the compositions of ribosomes of GBM cells in the tumour core and edge differ due to alternative RNA splicing. The acidic pH in the core switches before messenger RNA splicing of the ribosomal gene RPL22L1 towards the RPL22L1b isoform. This allows cells to survive acidosis, increases stemness and correlates with worse patient outcome. Mechanistically, RPL22L1b promotes RNA splicing by interacting with lncMALAT1 in the nucleus and inducing its degradation. Contrarily, in the tumour edge region, RPL22L1a interacts with ribosomes in the cytoplasm and upregulates the translation of multiple messenger RNAs including TP53. We found that the RPL22L1 isoform switch is regulated by SRSF4 and identified a compound that inhibits this process and decreases tumour growth. These findings demonstrate how distinct GBM cell populations arise during tumour growth. Targeting this mechanism may decrease GBM heterogeneity and facilitate therapy.

Here we describe the development and validation of a highly sensitive assay of antigen-specific IFN-γ production using real time quantitative PCR (qPCR) for two reporters--monokine-induced by IFN-γ (MIG) and the IFN-γ inducible protein-10 (IP10). We developed and validated the assay and applied it to the detection of CMV, HIV and Mycobacterium tuberculosis (MTB) specific responses, in a cohort of HIV co-infected patients. We compared the sensitivity of this assay to that of the ex vivo RD1 (ESAT-6 and CFP-10)-specific IFN-γ Elispot assay. We observed a clear quantitative correlation between the two assays (P