Search results for: long-acting reversible contraceptive

Authors: Igor B. Sivaev

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Design of molecular machines is an extraordinary growing and very important area of research that it was recognized by awarding Sauvage, Stoddart and Feringa the Nobel Prize in Chemistry in 2016 'for the design and synthesis of molecular machines'. Based on the type of motion being performed, molecular machines can be divided into two main types: molecular motors and molecular switches. Molecular switches are molecules or supramolecular complexes having bistability, i.e., the ability to exist in two or more stable forms, among which may be reversible transitions under external influence (heating, lighting, changing the medium acidity, the action of chemicals, exposure to magnetic or electric field). Molecular switches are the main structural element of any molecular electronics devices. Therefore, the design and the study of molecules and supramolecular systems capable of performing mechanical movement is an important and urgent problem of modern chemistry. There is growing interest in molecular switches and other devices of molecular electronics based on transition metal complexes; therefore choice of suitable stable organometallic unit is of great importance. An example of such unit is bis(dicarbollide) complexes of transition metals [3,3’-M(1,2-C₂B₉H₁₁)₂]ⁿ⁻. The control on the ligand rotation in such complexes can be reached by introducing substituents which could provide stabilization of certain rotamers due to specific interactions between the ligands, on the one hand, and which can participate as Lewis bases in complex formation with external metals resulting in a change in the rotation angle of the ligands, on the other hand. A series of isomeric methyl sulfide derivatives of cobalt bis(dicarbollide) complexes containing methyl sulfide substituents at boron atoms in different positions of the pentagonal face of the dicarbollide ligands [8,8’-(MeS)₂-3,3’-Co(1,2-C₂B₉H₁₀)₂]⁻, rac-[4,4’-(MeS)₂-3,3’-Co(1,2-C₂B₉H₁₀)₂]⁻ and meso-[4,7’-(MeS)₂-3,3’-Co(1,2-C₂B₉H₁₀)₂]⁻ were synthesized by the reaction of CoCl₂ with the corresponding methyl sulfide carborane derivatives [10-MeS-7,8-C₂B₉H₁₁)₂]⁻ and [10-MeS-7,8-C₂B₉H₁₁)₂]⁻. In the case of asymmetrically substituted cobalt bis(dicarbollide) complexes the corresponding rac- and meso-isomers were successfully separated by column chromatography as the tetrabutylammonium salts. The compounds obtained were studied by the methods of ¹H, ¹³C, and ¹¹B NMR spectroscopy, single crystal X-ray diffraction, cyclic voltammetry, controlled potential coulometry and quantum chemical calculations. It was found that in the solid state, the transoid- and gauche-conformations of the 8,8’- and 4,4’-isomers are stabilized by four intramolecular CH···S(Me)B hydrogen bonds each one (2.683-2.712 Å and 2.709-2.752 Å, respectively), whereas gauche-conformation of the 4,7’-isomer is stabilized by two intramolecular CH···S hydrogen bonds (2.699-2.711 Å). The existence of the intramolecular CH·S(Me)B hydrogen bonding in solutions was supported by the 1H NMR spectroscopy. These data are in a good agreement with results of the quantum chemical calculations. The corresponding iron and nickel complexes were synthesized as well. The reaction of the methyl sulfide derivatives of cobalt bis(dicarbollide) with various labile transition metal complexes results in rupture of intramolecular hydrogen bonds and complexation of the methyl sulfide groups with external metal. This results in stabilization of other rotational conformation of cobalt bis(dicarbollide) and can be used in design of molecular switches. This work was supported by the Russian Science Foundation (16-13-10331).

Keywords: molecular switches, NMR spectroscopy, single crystal X-ray diffraction, transition metal bis(dicarbollide) complexes, quantum chemical calculations

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Authors: Yi H. Wong, Li L. Chan, Chee O. Leong, Stephen Ambu, Joon W. Mak, Priyadashi S. Sahu

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Background: Acanthamoeba is a free-living opportunistic protist which is ubiquitously distributed in the environment. Virulent Acanthamoeba can cause fatal encephalitis in immunocompromised patients and potential blinding keratitis in immunocompetent contact lens wearers. Approximately 24 species have been identified but only the A. castellanii, A. polyphaga and A. culbertsoni are commonly associated with human infections. Until to date, the precise molecular basis for Acanthamoeba pathogenesis remains unclear. Previous studies reported that Acanthamoeba virulence can be diminished through prolonged axenic culture but revived through serial mouse passages. As no clear explanation on this reversible pathogenesis is established, hereby, we postulate that the epigenetic regulators, DNA-methyltransferases (DNMT) and histone-deacetylases (HDAC), could possibly be involved in granting the virulence plasticity of Acanthamoeba spp. Methods: Four rounds of mouse passages were conducted to revive the virulence potential of the virulence-attenuated Acanthamoeba castellanii strain (ATCC 50492). Briefly, each mouse (n=6/group) was inoculated intraperitoneally with Acanthamoebae cells (2x 105 trophozoites/mouse) and incubated for 2 months. Acanthamoebae cells were isolated from infected mouse organs by culture method and subjected to subsequent mouse passage. In vitro cytopathic, encystment and gelatinolytic assays were conducted to evaluate the virulence characteristics of Acanthamoebae isolates for each passage. PCR primers which targeted on the 2 members (DNMT1 and DNMT2) and 5 members (HDAC1 to 5) of the DNMT and HDAC gene families respectively were custom designed. Quantitative real-time PCR (qPCR) was performed to detect and quantify the relative expression of the two gene families in each Acanthamoeba isolates. Beta-tubulin of A. castellanii (Genbank accession no: XP_004353728) was included as housekeeping gene for data normalisation. PCR mixtures were also analyzed by electrophoresis for amplicons detection. All statistical analyses were performed using the paired one-tailed Student’s t test. Results: Our pathogenicity tests showed that the virulence-reactivated Acanthamoeba had a higher degree of cytopathic effect on vero cells, a better resistance to encystment challenge and a higher gelatinolytic activity which was catalysed by serine protease. qPCR assay showed that DNMT1 expression was significantly higher in the virulence-reactivated compared to the virulence-attenuated Acanthamoeba strain (p ≤ 0.01). The specificity of primers which targeted on DNMT1 was confirmed by sequence analysis of PCR amplicons, which showed a 97% similarity to the published DNA-methyltransferase gene of A. castellanii (GenBank accession no: XM_004332804.1). Out of the five primer pairs which targeted on the HDAC family genes, only HDAC4 expression was significantly difference between the two variant strains. In contrast to DNMT1, HDAC4 expression was much higher in the virulence-attenuated Acanthamoeba strain. Conclusion: Our mouse passages had successfully restored the virulence of the attenuated strain. Our findings suggested that DNA-methyltransferase (DNMT1) and histone deacetylase (HDAC4) expressions are associated with virulence potential of Acanthamoeba spp.

Keywords: acanthamoeba, DNA-methyltransferase, histone deacetylase, virulence-associated proteins

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Authors: Rui Pedro de Sousa Guimarães Ferreira, Carlos Alberto Maia Domínguez

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Despite the ambitions to achieve climate neutrality by 2050, to fulfill the Paris Agreement's goals, the building and construction sector remains one of the most resource-intensive and greenhouse gas-emitting industries in the world, accounting for 40% of worldwide CO ₂ emissions. Over the past few decades, globalization and population growth have led to an exponential rise in demand in the housing market and, by extension, in the building industry. Considering this housing crisis, it is obvious that we will not stop building in the near future. However, the transition, which has already started, is challenging and complex because it calls for the worldwide participation of numerous organizations in altering how building systems, which have been a part of our everyday existence for over a century, are used. Wood is one of the alternatives that is most frequently used nowadays (under responsible forestry conditions) because of its physical qualities and, most importantly, because it produces fewer carbon emissions during manufacturing than steel or concrete. Furthermore, as wood retains its capacity to store CO ₂ after application and throughout the life of the building, working as a natural carbon filter, it helps to reduce greenhouse gas emissions. After a century-long focus on other materials, in the last few decades, technological advancements have made it possible to innovate systems centered around the use of wood. However, there are still some questions that require further exploration. It is necessary to standardize production and manufacturing processes based on prefabrication and modularization principles to achieve greater precision and optimization of the solutions, decreasing building time, prices, and waste from raw materials. In addition, this approach will make it possible to develop new architectural solutions to solve the rigidity and irreversibility of buildings, two of the most important issues facing housing today. Most current models are still created as inflexible, fixed, monofunctional structures that discourage any kind of regeneration, based on matrices that sustain the conventional family's traditional model and are founded on rigid, impenetrable compartmentalization. Adaptability and flexibility in housing are, and always have been, necessities and key components of architecture. People today need to constantly adapt to their surroundings and themselves because of the fast-paced, disposable, and quickly obsolescent nature of modern items. Migrations on a global scale, different kinds of co-housing, or even personal changes are some of the new questions that buildings have to answer. Designing with the reversibility of construction systems and materials in mind not only allows for the concept of "looping" in construction, with environmental advantages that enable the development of a circular economy in the sector but also unleashes multiple social benefits. In this sense, it is imperative to develop prefabricated and modular construction systems able to address the formalization of a reversible proposition that adjusts to the scale of time and its multiple reformulations, many of which are unpredictable. We must allow buildings to change, grow, or shrink over their lifetime, respecting their nature and, finally, the nature of the people living in them. It´s the ability to anticipate the unexpected, adapt to social factors, and take account of demographic shifts in society to stabilize communities, the foundation of real innovative sustainability.

Keywords: modular, timber, flexibility, housing

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Authors: Nurlan Smagulov, Aiman Konkabayeva, Akerke Sadykova, Arailym Serik

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Introduction. Adverse environmental factors do not immediately lead to pathological changes in the body. They can exert the growth of pre-pathology characterized by shifts in physiological, biochemical, immunological and other indicators of the body state. These disorders are unstable, reversible and indicative of body reactions. There is an opportunity to objectively judge the internal structure of the adaptive body reactions at the level of individual organs and systems. In order to obtain a stable response of the body to the chronic effects of unfavorable environmental factors of low intensity (compared to production environment factors), a time called the «lag time» is needed. The obtained results without considering this factor distort reality and, for the most part, cannot be a reliable statement of the main conclusions in any work. A technique is needed to reduce methodological errors and combine mathematical logic using statistical methods and a medical point of view, which ultimately will affect the obtained results and avoid a false correlation. Objective. Development of a methodology for assessing and predicting the environmental factors impact on the population health considering the «lag time.» Methods. Research objects: environmental and population morbidity indicators. The database on the environmental state was compiled from the monthly newsletters of Kazhydromet. Data on population morbidity were obtained from regional statistical yearbooks. When processing static data, a time interval (lag) was determined for each «argument-function» pair. That is the required interval, after which the harmful factor effect (argument) will fully manifest itself in the indicators of the organism's state (function). The lag value was determined by cross-correlation functions of arguments (environmental indicators) with functions (morbidity). Correlation coefficients (r) and their reliability (t), Fisher's criterion (F) and the influence share (R2) of the main factor (argument) per indicator (function) were calculated as a percentage. Results. The ecological situation of an industrially developed region has an impact on health indicators, but it has some nuances. Fundamentally opposite results were obtained in the mathematical data processing, considering the «lag time». Namely, an expressed correlation was revealed after two databases (ecology-morbidity) shifted. For example, the lag period was 4 years for dust concentration, general morbidity, and 3 years – for childhood morbidity. These periods accounted for the maximum values of the correlation coefficients and the largest percentage of the influencing factor. Similar results were observed in relation to the concentration of soot, dioxide, etc. The comprehensive statistical processing using multiple correlation-regression variance analysis confirms the correctness of the above statement. This method provided the integrated approach to predicting the degree of pollution of the main environmental components to identify the most dangerous combinations of concentrations of leading negative environmental factors. Conclusion. The method of assessing the «environment-public health» system (considering the «lag time») is qualitatively different from the traditional (without considering the «lag time»). The results significantly differ and are more amenable to a logical explanation of the obtained dependencies. The method allows presenting the quantitative and qualitative dependence in a different way within the «environment-public health» system.

Keywords: ecology, morbidity, population, lag time

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Authors: Osman Adiguzel

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Shape-memory alloys are a new class of functional materials with a peculiar property known as shape memory effect. These alloys return to a previously defined shape on heating after deformation in low temperature product phase region and take place in a class of functional materials due to this property. The origin of this phenomenon lies in the fact that the material changes its internal crystalline structure with changing temperature. Shape memory effect is based on martensitic transitions, which govern the remarkable changes in internal crystalline structure of materials. Martensitic transformation, which is a solid state phase transformation, occurs in thermal manner in material on cooling from high temperature parent phase region. This transformation is governed by changes in the crystalline structure of the material. Shape memory alloys cycle between original and deformed shapes in bulk level on heating and cooling, and can be used as a thermal actuator or temperature-sensitive elements due to this property. Martensitic transformations usually occur with the cooperative movement of atoms by means of lattice invariant shears. The ordered parent phase structures turn into twinned structures with this movement in crystallographic manner in thermal induced case. The twinned martensites turn into the twinned or oriented martensite by stressing the material at low temperature martensitic phase condition. The detwinned martensite turns into the parent phase structure on first heating, first cycle, and parent phase structures turn into the twinned and detwinned structures respectively in irreversible and reversible memory cases. On the other hand, shape memory materials are very important and useful in many interdisciplinary fields such as medicine, pharmacy, bioengineering, metallurgy and many engineering fields. The choice of material as well as actuator and sensor to combine it with the host structure is very essential to develop main materials and structures. Copper based alloys exhibit this property in metastable beta-phase region, which has bcc-based structures at high temperature parent phase field, and these structures martensitically turn into layered complex structures with lattice twinning following two ordered reactions on cooling. Martensitic transition occurs as self-accommodated martensite with inhomogeneous shears, lattice invariant shears which occur in two opposite directions, <110 > -type directions on the {110}-type plane of austenite matrix which is basal plane of martensite. This kind of shear can be called as {110}<110> -type mode and gives rise to the formation of layered structures, like 3R, 9R or 18R depending on the stacking sequences on the close-packed planes of the ordered lattice. In the present contribution, x-ray diffraction and transmission electron microscopy (TEM) studies were carried out on two copper based alloys which have the chemical compositions in weight; Cu-26.1%Zn 4%Al and Cu-11%Al-6%Mn. X-ray diffraction profiles and electron diffraction patterns reveal that both alloys exhibit super lattice reflections inherited from parent phase due to the displacive character of martensitic transformation. X-ray diffractograms taken in a long time interval show that locations and intensities of diffraction peaks change with the aging time at room temperature. In particular, some of the successive peak pairs providing a special relation between Miller indices come close each other.

Keywords: Shape memory effect, martensite, twinning, detwinning, self-accommodation, layered structures

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Authors: Thaminda Liyanage, Chamila Shamika Kurukulasuriya

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Introduction: Morbid obesity has been successfully treated with bariatric surgery for over 60 years. Although operative procedures have improved and associated complications have reduced substantially, surgery still carries the risk of post-operative malabsorption, malnutrition and a range of gastrointestinal disorders. Overweight by itself can impair libido in both sexes and cause erectile dysfunction in males by inducing a state of hypogonadotropic hypogonadism, proportional to the degree of obesity. Impact of weight reduction on libido and sexual activity remains controversial, however it is broadly accepted that weight loss improves sexual drive. Zinc deficiency, subsequent to malabsorption, may lead to impaired testosterone synthesis in men while excessive and/or rapid weight loss in females may result in reversible amenorrhoea leading to sub-fertility. Methods: We describe a 37 year old male, 6 years post Roux-en-Y gastric bypass surgery, who presented with erectile dysfunction, loss of libido, worsening fatigue and generalized weakness for 4 months. He also complained of constipation and frequent muscle cramps but denied having headache, vomiting or visual disturbances. Patient had lost 38 kg of body weight post gastric bypass surgery over four years {135kg (BMI 42.6 kg/m2) to 97 kg (BMI 30.6 kg/m2)} and the weight had been stable for past two years. He had no recognised co-morbidities at the time of the surgery and noted marked improvement in general wellbeing, physical fitness and psychological confident post surgery, up until four months before presentation. Clinical examination revealed dry pale skin with normal body hair distribution, no thyroid nodules or goitre, normal size testicles and normal neurological examination with no visual field defects or diplopia. He had low serum testosterone, follicular stimulating hormone (FSH), luteinizing hormone (LH), T3, T4, thyroid stimulating hormone (TSH), insulin like growth factor 1 (IGF-1) and 24-hour urine cortisol levels. Serum cortisol demonstrated an appropriate rise to ACTH stimulation test but growth hormone (GH) failed increase on insulin tolerance test. Other biochemical and haematological studies were normal, except for low zinc and folate with minimally raised liver enzymes. MRI scan of the head confirmed a solid pituitary mass with no mass effect on optic chiasm. Results: In this patient clinical, biochemical and radiological findings were consistent with anterior pituitary dysfunction. However, there were no features of raised intracranial pressure or neurological compromise. He was commenced on appropriate home replacement therapy and referred for neurosurgical evaluation. Patient reported marked improvement in his symptoms, specially libido and erectile dysfunction, on subsequent follow up visits. Conclusion: Sexual dysfunction coupled with non specific constitutional symptoms has multiple aetiologies. Clinical symptoms out of proportion to nutritional deficiencies post bariatric surgery should be thoroughly investigated. Close long term follow up is crucial for overall success.

Keywords: obesity, bariatric surgery, erectile dysfunction, loss of libido

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Authors: M. Kadela

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The load caused by the traffic movement should be transferred in the road constructions in a harmless way to the pavement as follows: − on the stiff upper layers of the structure (e.g. layers of asphalt: abrading and binding), and − through the layers of principal and secondary substructure, − on the subsoil, directly or through an improved subsoil layer. Reliable description of the interaction proceeding in a system “road construction – subsoil” should be in such case one of the basic requirements of the assessment of the size of internal forces of structure and its durability. Analyses of road constructions are based on: − elements of mechanics, which allows to create computational models, and − results of the experiments included in the criteria of fatigue life analyses. Above approach is a fundamental feature of commonly used mechanistic methods. They allow to use in the conducted evaluations of the fatigue life of structures arbitrarily complex numerical computational models. Considering the work of the system “road construction – subsoil”, it is commonly accepted that, as a result of repetitive loads on the subsoil under pavement, the growth of relatively small deformation in the initial phase is recognized, then this increase disappears, and the deformation takes the character completely reversible. The reliability of calculation model is combined with appropriate use (for a given type of analysis) of constitutive relationships. Phenomena occurring in the initial stage of the system “road construction – subsoil” is unfortunately difficult to interpret in the modeling process. The classic interpretation of the behavior of the material in the elastic-plastic model (e-p) is that elastic phase of the work (e) is undergoing to phase (e-p) by increasing the load (or growth of deformation in the damaging structure). The paper presents the essence of the calibration process of cooperating subsystem in the calculation model of the system “road construction – subsoil”, created for the mechanistic analysis. Calibration process was directed to show the impact of applied constitutive models on its deformation and stress response. The proper comparative base for assessing the reliability of created. This work was supported by the on-going research project “Stabilization of weak soil by application of layer of foamed concrete used in contact with subsoil” (LIDER/022/537/L-4/NCBR/2013) financed by The National Centre for Research and Development within the LIDER Programme. M. Kadela is with the Department of Building Construction Elements and Building Structures on Mining Areas, Building Research Institute, Silesian Branch, Katowice, Poland (phone: +48 32 730 29 47; fax: +48 32 730 25 22; e-mail: m.kadela@ itb.pl). models should be, however, the actual, monitored system “road construction – subsoil”. The paper presents too behavior of subsoil under cyclic load transmitted by pavement layers. The response of subsoil to cyclic load is recorded in situ by the observation system (sensors) installed on the testing ground prepared for this purpose, being a part of the test road near Katowice, in Poland. A different behavior of the homogeneous subsoil under pavement is observed for different seasons of the year, when pavement construction works as a flexible structure in summer, and as a rigid plate in winter. Albeit the observed character of subsoil response is the same regardless of the applied load and area values, this response can be divided into: - zone of indirect action of the applied load; this zone extends to the depth of 1,0 m under the pavement, - zone of a small strain, extending to about 2,0 m.

Keywords: road structure, constitutive model, calculation model, pavement, soil, FEA, response of soil, monitored system

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Authors: Pauline Nyssen, Ange Mouithys-Mickalad, Maryse Hoebeke

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Inflammation is a complex physiological phenomenon involving chemical and enzymatic mechanisms. Polymorphonuclear neutrophil leukocytes (PMNs) play an important role by producing reactive oxygen species (ROS) and releasing myeloperoxidase (MPO), a pro-oxidant enzyme. Released both in the phagolysosome and the extracellular medium, MPO produces during its peroxidase and halogenation cycles oxidant species, including hypochlorous acid, involved in the destruction of pathogen agents, like bacteria or viruses. Inflammatory pathologies, like rheumatoid arthritis, atherosclerosis induce an excessive stimulation of the PMNs and, therefore, an uncontrolled release of ROS and MPO in the extracellular medium, causing severe damages to the surrounding tissues and biomolecules such as proteins, lipids, and DNA. The treatment of chronic inflammatory pathologies remains a challenge. For many years, MPO has been used as a target for the development of effective treatments. Numerous studies have been focused on the design of new drugs presenting more efficient MPO inhibitory properties. However, some designed inhibitors can be toxic. An alternative consists of assessing the potential inhibitory action of clinically-known molecules, having antioxidant activity. Propofol, 2,6-diisopropyl phenol, which is used as an intravenous anesthetic agent, meets these requirements. Besides its anesthetic action employed to induce a sedative state during surgery or in intensive care units, propofol and its injectable form Diprivan indeed present antioxidant properties and act as ROS and free radical scavengers. A study has also evidenced the ability of propofol to inhibit the formation of the neutrophil extracellular traps fibers, which are important to trap pathogen microorganisms during the inflammation process. The aim of this study was to investigate the potential inhibitory action mechanism of propofol and Diprivan on MPO activity. To go into the anti-inflammatory action of propofol in-depth, two of its oxidative derivatives, 2,6-diisopropyl-1,4-p-benzoquinone (PPFQ) and 3,5,3’,5’-tetra isopropyl-(4,4’)-diphenoquinone (PPFDQ), were studied regarding their inhibitory action. Specific immunological extraction followed by enzyme detection (SIEFED) and molecular modeling have evidenced the low anti-catalytic action of propofol. Stopped-flow absorption spectroscopy and direct MPO activity analysis have proved that propofol acts as a reversible MPO inhibitor by interacting as a reductive substrate in the peroxidase cycle and promoting the accumulation of redox compound II. Overall, Diprivan exhibited a weaker inhibitory action than the active molecule propofol. In contrast, PPFQ seemed to bind and obstruct the enzyme active site, preventing the trigger of the MPO oxidant cycles. PPFQ induced a better chlorination cycle inhibition at basic and neutral pH in comparison to propofol. PPFDQ did not show any MPO inhibition activity. The three interest molecules have also demonstrated their inhibition ability on an important step of the inflammation pathway, the PMNs superoxide anions production, thanks to EPR spectroscopy and chemiluminescence. In conclusion, propofol presents an interesting immunomodulatory activity by acting as a reductive substrate in the peroxidase cycle of MPO, slowing down its activity, whereas PPFQ acts more as an anti-catalytic substrate. Although PPFDQ has no impact on MPO, it can act on the inflammation process by inhibiting the superoxide anions production by PMNs.

Keywords: Diprivan, inhibitor, myeloperoxidase, propofol, spectroscopy

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Authors: Oluwaseun Adeleke, Samuel O. Ikani, Simeon Christian Chukwu, Fidelis Edet, Anthony Nwala, Mopelola Raji, Simeon Christian Chukwu

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Background: Health service providers are offered in-service training periodically to strengthen their ability to deliver services that are ethical, quality, timely and safe. Not all capacity-building courses have successfully resulted in intended service delivery outcomes because of poor training content, design, approach, and ambiance. The Delivering Innovations in Selfcare (DISC) project developed a Moment of Truth innovation, which is a proven training model focused on improving consumer/provider interaction that leads to an increase in the voluntary uptake of subcutaneous depot medroxyprogesterone acetate (DMPA-SC) self-injection among women who opt for injectable contraception. Methodology: Six months after training on a moment of truth (MoT) training manual, the project conducted two intensive rounds of qualitative data collection and triangulation that included provider, client, and community mobilizer interviews, facility observations, and routine program data collection. Respondents were sampled according to a convenience sampling approach, and data collected was analyzed using a codebook and Atlas-TI. Providers and clients were interviewed to understand their experience, perspective, attitude, and awareness about the DMPA-SC self-inject. Data were collected from 12 health facilities in three states – eight directly trained and four cascades trained. The research team members came together for a participatory analysis workshop to explore and interpret emergent themes. Findings: Quality-of-service delivery and performance outcomes were observed to be significantly better in facilities whose providers were trained directly trained by the DISC project than in sites that received indirect training through master trainers. Facilities that were directly trained recorded SI proportions that were twice more than in cascade-trained sites. Direct training comprised of full-day and standalone didactic and interactive sessions constructed to evoke commitment, passion and conviction as well as eliminate provider bias and misconceptions in providers by utilizing human interest stories and values clarification exercises. Sessions also created compelling arguments using evidence and national guidelines. The training also prioritized demonstration sessions, utilized job aids, particularly videos, strengthened empathetic counseling – allaying client fears and concerns about SI, trained on positioning self-inject first and side effects management. Role plays and practicum was particularly useful to enable providers to retain and internalize new knowledge. These sessions provided experiential learning and the opportunity to apply one's expertise in a supervised environment where supportive feedback is provided in real-time. Cascade Training was often a shorter and abridged form of MoT training that leveraged existing training already planned by master trainers. This training was held over a four-hour period and was less emotive, focusing more on foundational DMPA-SC knowledge such as a reorientation to DMPA-SC, comparison of DMPA-SC variants, counseling framework and skills, data reporting and commodity tracking/requisition – no facility practicums. Training on self-injection was not as robust, presumably because they were not directed at methods in the contraceptive mix that align with state/organizational sponsored objectives – in this instance, fostering LARC services. Conclusion: To achieve better performance outcomes, consideration should be given to providing training that prioritizes practice-based and emotive content. Furthermore, a firm understanding and conviction about the value training offers improve motivation and commitment to accomplish and surpass service-related performance outcomes.

Keywords: training, performance outcomes, innovation, family planning, contraception, DMPA-SC, self-care, self-injection.

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Authors: Oluwaseun Adeleke, Samuel O. Ikani, Fidelis Edet, Anthony Nwala, Mopelola Raji, Simeon Christian Chukwu

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Background The Delivering Innovations in Selfcare (DISC) project promotes universal access to quality selfcare services beginning with subcutaneous depot medroxy progesterone acetate (DMPA-SC) contraceptive self-injection (SI) option. Self-inject (SI) offers women a highly effective and convenient option that saves them frequent trips to providers. Its increased use has the potential to improve the efficiency of an overstretched healthcare system by reducing provider workloads. State Social and Behavioral Change Communications (SBCC) Officers lead project demand creation and service delivery innovations that have resulted in significant increases in SI uptake among women who opt for injectables. Strategies Service Delivery Innovations The implementation of the "Moment of Truth (MoT)" innovation helped providers overcome biases and address client fear and reluctance to self-inject. Bi-annual program audits and supportive mentoring visits helped providers retain their competence and motivation. Proper documentation, tracking, and replenishment of commodities were ensured through effective engagement with State Logistics Units. The project supported existing state monitoring and evaluation structures to effectively record and report subcutaneous depot medroxy progesterone acetate (DMPA-SC) service utilization. Demand creation Innovations SBCC Officers provide oversight, routinely evaluate performance, trains, and provides feedback for the demand creation activities implemented by community mobilizers (CMs). The scope and intensity of training given to CMs affect the outcome of their work. The project operates a demand creation model that uses a schedule to inform the conduct of interpersonal and group events. Health education sessions are specifically designed to counter misinformation, address questions and concerns, and educate target audience in an informed choice context. The project mapped facilities and their catchment areas and enlisted the support of identified influencers and gatekeepers to enlist their buy-in prior to entry. Each mobilization event began with pre-mobilization sensitization activities, particularly targeting male groups. Context-specific interventions were informed by the religious, traditional, and cultural peculiarities of target communities. Mobilizers also support clients to engage with and navigate online digital Family Planning (FP) online portals such as DiscoverYourPower website, Facebook page, digital companion (chat bot), interactive voice response (IVR), radio and television (TV) messaging. This improves compliance and provides linkages to nearby facilities. Results The project recorded 136,950 self-injection (SI) visits and a self-injection (SI) proportion rate that increased from 13 percent before the implementation of interventions in 2021 to 62 percent currently. The project cost-effectively demonstrated catalytic impact by leveraging state and partner resources, institutional platforms, and geographic scope to scale up interventions. The project also cost effectively demonstrated catalytic impact by leveraging on the state and partner resources, institutional platforms, and geographic scope to sustainably scale-up these strategies. Conclusion Using evidence-informed iterations of service delivery and demand creation models have been useful to significantly drive self-injection (SI) uptake. It will be useful to consider this implementation model during program design. Contemplation should also be given to systematic and strategic execution of strategies to optimize impact.

Keywords: family planning, contraception, DMPA-SC, self-care, self-injection, innovation, service delivery, demand creation.

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Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

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Cardiac hypertrophy arises in response to persistent increases in hemodynamic loads. In comparison, diabetic cardiomyopathy is defined by an abnormal myocardial changes without other cardiac-related risk factors. Pathological cardiac hypertrophy and myocardial remodeling are hallmarks of cardiovascular diseases and are risk factors for heart failure. The transcription factor forkhead box class O (FOXOs) can protect heart tissue by hostile oxidative stress and stimulating apoptosis and autophagy. FOXO proteins, as sensitive elements and mediators in response to environmental changes, have been revealed to prevent and inverse cardiac hypertrophy. FOXOs are inhibited by insulin and are critical mediators of insulin action. Insulin deficiency and uncontrolled diabetes lead to a catabolic state. FOXO1 acts downstream of the insulin-dependent pathways, which are dysregulated in diabetes. It regulates cardiomyocyte hypertrophy downstream of IGF1R/PI3K/Akt activation, which are critical regulators of cardiac hypertrophy. The complex network of signaling pathways comprising insulin/IGF-1 signaling, AMPK, JNK, and Sirtuins regulate the development of cardiovascular dysfunction by modulating the activity of FOXOs. Insulin receptors and IGF1R act via the PI3k/Akt and the MAPK/ERK pathways. Activation of Akt in response to insulin or IGF-1 induces phosphorylation of FOXOs. Increased protein synthesis induced by activation of the IGF-I/Akt/mTOR signaling pathway leads to hypertrophy. This pathway and the myostatin/Smad pathway are potent negative muscle development regulators. In cardiac muscle, insulin receptor substrates (IRS)-1 or IRS-2 activates the Akt signaling pathway and inactivate FOXO1. Under metabolic stress, p38 MAPK promotes degradation of IRS-1 and IRS-2 in cardiac myocytes and activates FOXO1, leading to cardiomyopathy. Sirt1 and FOXO1 interaction play an essential role in starvation-induced autophagy in cardiac metabolism. Inhibition of Angiotensin-II induced cardiomyocyte hypertrophy is associated with reduced FOXO1 acetylation and activation of Sirt1. The NF-κB, ERK, and FOXOs are de-acetylated by SIRT1. De-acetylation of FOXO1 induces the expression of genes involved in autophagy and stimulates autophagy flux. Therefore, under metabolic stress, FOXO1 can cause diabetic cardiomyopathy. The overexpression of FOXO1 leads to decreased cardiomyocyte size and suppresses cardiac hypertrophy through inhibition of the calcineurin–NFAT pathway. Diabetes mellitus is associated with elevation of O-GlcNAcylation. Some of its binding partners regulate the substrate selectivity of O-GlcNAc transferase (OGT). O-GlcNAcylation of essential contractile proteins may inhibit protein-protein interactions, reduce calcium sensitivity, and modulate contractile function. Uridine diphosphate (UDP)-GlcNAc is the obligatory substrate of OGT, which catalyzes a reversible post-translational protein modification. The increase of O-GlcNAcylation is accompanied by impaired cardiac hypertrophy in diabetic hearts. Inhibition of O-GlcNAcylation blocks activation of ERK1/2 and hypertrophic growth. O-GlcNAc modification on NFAT is required for its translocation from the cytosol to the nucleus, where NFAT stimulates the transcription of various hypertrophic genes. Inhibition of O-GlcNAcylation dampens NFAT-induced cardiac hypertrophic growth. Transcriptional activity of FOXO1 is enriched by improved O-GlcNAcylation upon high glucose stimulation or OGT overexpression. In diabetic conditions, the modification of FOXO1 by O-GlcNAc is promoted in cardiac troponin I and myosin light chain 2. Therefore targeting O-GlcNAcylation represents a potential therapeutic option to prevent hypertrophy in the diabetic heart.

Keywords: diabetes, cardiac hypertrophy, O-GlcNAcylation, FOXO1, Akt, PI3K, AMPK, insulin

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Authors: Agman Gupta, Rajashekar Badam, Noriyoshi Matsumi

Abstract:

Introduction: Recently, silicon has been recognized as one of the potential alternatives as anode active material in Li-ion batteries (LIBs) to replace the conventionally used graphite anodes. Silicon is abundantly present in the nature, it can alloy with lithium metal, and has a higher theoretical capacity (~4200 mAhg-1) that is approximately 10 times higher than graphite. However, because of a large volume expansion (~400%) upon repeated de-/alloying, the pulverization of Si particles causes the exfoliation of electrode laminate leading to the loss of electrical contact and adversely affecting the formation of solid-electrolyte interface (SEI).1 Functional polymers as binders have emerged as a competitive strategy to mitigate these drawbacks and failure mechanism of silicon anodes.1 A variety of aqueous/non-aqueous polymer binders like sodium carboxy-methyl cellulose (CMC-Na), styrene butadiene rubber (SBR), poly(acrylic acid), and other variants like mussel inspired binders have been investigated to overcome these drawbacks.1 However, there are only a few reports that mention the attempt of addressing all the drawbacks associated with silicon anodes effectively using a single novel functional polymer system as a binder. In this regard, here, we report a novel highly robust n-type bisiminoacenaphthenequinone (BIAN)-paraphenylene-based crosslinked polymer as a binder for Si anodes in lithium-ion batteries (Fig. 1). On its application, crosslinked-BIAN binder was evaluated to provide mechanical robustness to the large volume expansion of Si particles, maintain electrical conductivity within the electrode laminate, and facilitate in the formation of a thin SEI by restricting the extent of electrolyte decomposition on the surface of anode. The fabricated anodic half-cells were evaluated electrochemically for their rate capability, cyclability, and discharge capacity. Experimental: The polymerized BIAN (P-BIAN) copolymer was synthesized as per the procedure reported by our group.2 The synthesis of crosslinked P-BIAN: a solution of P-BIAN copolymer (1.497 g, 10 mmol) in N-methylpyrrolidone (NMP) (150 ml) was set-up to stir under reflux in nitrogen atmosphere. To this, 1,6-dibromohexane (5 mmol, 0.77 ml) was added dropwise. The resultant reaction mixture was stirred and refluxed at 150 °C for 24 hours followed by refrigeration for 3 hours at 5 °C. The product was obtained by evaporating the NMP solvent under reduced pressure and drying under vacuum at 120 °C for 12 hours. The obtained product was a black colored sticky compound. It was characterized by 1H-NMR, XPS, and FT-IR techniques. Results and Discussion: The N 1s XPS spectrum of the crosslinked BIAN polymer showed two characteristic peaks corresponding to the sp2 hybridized nitrogen (-C=N-) at 399.6 eV of the diimine backbone in the BP and quaternary nitrogen at 400.7 eV corresponding to the crosslinking of BP via dibromohexane. The DFT evaluation of the crosslinked BIAN binder showed that it has a low lying lowest unoccupied molecular orbital (LUMO) that enables it to get doped in the reducing environment and influence the formation of a thin (SEI). Therefore, due to the mechanically robust crosslinked matrices as well as its influence on the formation of a thin SEI, the crosslinked BIAN binder stabilized the Si anode-based half-cell for over 1000 cycles with a reversible capacity of ~2500 mAhg-1 and ~99% capacity retention as shown in Fig. 2. The dynamic electrochemical impedance spectroscopy (DEIS) characterization of crosslinked BIAN-based anodic half-cell confirmed that the SEI formed was thin in comparison with the conventional binder-based anodes. Acknowledgement: We are thankful to the financial support provided by JST-Mirai Program, Grant Number: JP18077239

Keywords: self-healing binder, n-type binder, thin solid-electrolyte interphase (SEI), high-capacity silicon anodes, low-LUMO

Procedia PDF Downloads 169

Authors: L. Malic, X. Zhang, D. Brassard, L. Clime, J. Daoud, C. Luebbert, V. Barrere, A. Boutin, S. Bidawid, N. Corneau, J. Farber, T. Veres

Abstract:

The incidence of infections caused by foodborne pathogens such as Listeria monocytogenes (L. monocytogenes) poses a great potential threat to public health and safety. These issues are further exacerbated by legal repercussions due to “zero tolerance” food safety standards adopted in developed countries. Unfortunately, a large number of related disease outbreaks are caused by pathogens present in extremely low counts currently undetectable by available techniques. The development of highly sensitive and rapid detection of foodborne pathogens is therefore crucial, and requires robust and efficient pre-analytical sample preparation. Immunomagnetic separation is a popular approach to sample preparation. Microfluidic chips combined with external magnets have emerged as viable high throughput methods. However, external magnets alone are not suitable for the capture of nanoparticles, as very strong magnetic fields are required. Devices that incorporate externally applied magnetic field and microstructures of a soft magnetic material have thus been used for local field amplification. Unfortunately, very complex and costly fabrication processes used for integration of soft magnetic materials in the reported proof-of-concept devices would prohibit their use as disposable tools for food and water safety or diagnostic applications. We present a sample preparation magnetic microfluidic device implemented in low-cost thermoplastic polymers using fabrication techniques suitable for mass-production. The developed magnetic capture chip (M-chip) was employed for rapid capture and release of L. monocytogenes conjugated to immunomagnetic nanoparticles (IMNs) in buffer and beef filtrate. The M-chip relies on a dense array of Nickel-coated high-aspect ratio pillars for capture with controlled magnetic field distribution and a microfluidic channel network for sample delivery, waste, wash and recovery. The developed Nickel-coating process and passivation allows generation of switchable local perturbations within the uniform magnetic field generated with a pair of permanent magnets placed at the opposite edges of the chip. This leads to strong and reversible trapping force, wherein high local magnetic field gradients allow efficient capture of IMNs conjugated to L. monocytogenes flowing through the microfluidic chamber. The experimental optimization of the M-chip was performed using commercially available magnetic microparticles and fabricated silica-coated iron-oxide nanoparticles. The fabricated nanoparticles were optimized to achieve the desired magnetic moment and surface functionalization was tailored to allow efficient capture antibody immobilization. The integration, validation and further optimization of the capture and release protocol is demonstrated using both, dead and live L. monocytogenes through fluorescence microscopy and plate- culture method. The capture efficiency of the chip was found to vary as function of listeria to nanoparticle concentration ratio. The maximum capture efficiency of 30% was obtained and the 24-hour plate-culture method allowed the detection of initial sample concentration of only 16 cfu/ml. The device was also very efficient in concentrating the sample from a 10 ml initial volume. Specifically, 280% concentration efficiency was achieved in 17 minutes only, demonstrating the suitability of the system for food safety applications. In addition, flexible design and low-cost fabrication process will allow rapid sample preparation for applications beyond food and water safety, including point-of-care diagnosis.

Keywords: array of pillars, bacteria isolation, immunomagnetic sample preparation, polymer microfluidic device

Procedia PDF Downloads 280