Experience of Western Herbal Medicine practitioners in supporting brain health in mid-life and older patients: a qualitative research study

Introduction and Aims Dementia is a public health and social care priority, necessitating multi-domain preventative healthcare strategies in at-risk populations The evidence on the use of herbs in addressing neurological, psychological, metabolic and cardiovascular conditions implicated in dementia pathology, and the holistic therapeutic and philosophical attributes of its clinical practice suggest a role for Western herbal medicine (WHM) in primary prevention and healthy brain ageing. The aim of this qualitative study was to explore the current real-life application of WHM in supporting cognitive and vascular brain health in mid-life and older patients. Methods Three WHM practitioners were recruited using purposive sampling and a set of inclusion criteria. Semi-structured interviews were used to explore their herbal and therapeutic management approach; and gauge their views on the preventative role of WHM in the assay group. Data from taped interview transcripts, providing a total of 110 minutes, were analysed using simple thematic analysis to identify main themes in the practitioners’ narratives. Results Four themes emerged from the practitioners’ narratives of their experience of working with the assay group: the memory loss and cognitive function issues, as well as other conditions implicated in dementia pathology their patients presented with; their use of herbs as well as dietary and lifestyle recommendations in the individualised therapeutic management of those presentations; patient compliance and other issues of working with the target patient group; and the potential role for WHM in managing brain health in an aging population within the wider healthcare ecosystem. Discussion The small exploratory study is the first of its kind attempting to capture the experience of WMH practitioners working with brain health in mid-life and elderly patients. It provides some important insights into the current WHM therapeutic practice and professional competency and some indicators for its future role: WMH’s unique attributes of individualisation and plurality of practice, patient-responsive treatment and the collaborative patient-practitioner therapeutic relationship. Although its findings cannot be generalised, the study provides a reference for future deductive qualitative research. In particular, it warrants further investigation into the role that WHM can play alongside conventional medicine in managing brain health in an aging population

Sequence analysis methods for the design of cancer vaccines that target tumor-specific mutant antigens (neoantigens)

The human adaptive immune system is programmed to distinguish between self and non-self proteins and if trained to recognize markers unique to a cancer, it may be possible to stimulate the selective destruction of cancer cells. Therapeutic cancer vaccines aim to boost the immune system by selectively increasing the population of T cells specifically targeted to the tumor-unique antigens, thereby initiating cancer cell death.. In the past, this approach has primarily focused on targeted selection of ‘shared’ tumor antigens, found across many patients. The advent of massively parallel sequencing and specialized analytical approaches has enabled more efficient characterization of tumor-specific mutant antigens, or neoantigens. Specifically, methods to predict which tumor-specific mutant peptides (neoantigens) can elicit anti-tumor T cell recognition improve predictions of immune checkpoint therapy response and identify one or more neoantigens as targets for personalized vaccines. Selecting the best/most immunogenic neoantigens from a large number of mutations is an important challenge, in particular in cancers with a high mutational load, such as melanomas and smoker-associated lung cancers. To address such a challenging task, Chapter 1 of this thesis describes a genome-guided in silico approach to identifying tumor neoantigens that integrates tumor mutation and expression data (DNA- and RNA-Seq). The cancer vaccine design process, from read alignment to variant calling and neoantigen prediction, typically assumes that the genotype of the Human Reference Genome sequence surrounding each somatic variant is representative of the patient’s genome sequence, and does not account for the effect of nearby variants (somatic or germline) in the neoantigenic peptide sequence. Because the accuracy of neoantigen identification has important implications for many clinical trials and studies of basic cancer immunology, Chapter 2 describes and supports the need for patient-specific inclusion of proximal variants to address this previously oversimplified assumption in the identification of neoantigens. The method of neoantigen identification described in Chapter 1 was subsequently extended (Chapter 3) and improved by the addition of a modular workflow that aids in each component of the neoantigen prediction process from neoantigen identification, prioritization, data visualization, and DNA vaccine design. These chapters describe massively parallel sequence analysis methods that will help in the identification and subsequent refinement of patient-specific antigens for use in personalized immunotherapy

Development of a Cloning Strategy to Enable the Isolation of Novel Membrane Proteins

The aim of the project was to develop a cloning strategy for the isolation of novel membrane proteins. The scheme evolved from the surface antigen screening system developed by Seed and Aruffo (1987). The system was adapted to enable the cloning of cDNAs coding for membrane proteins to which no antibodies exist. This was achieved by taking a previously cloned membrane protein gene (CD2), deleting its transmembrane (Tm) and cytosolic regions, and replacing them with the polylinker and stuffer sequences of CDM8. cDNAs were then sub-cloned into this expression vector to generate a fusion library. which was then screened for surface expression of the CD2 protein

Optimisation of dietary n-3 and n-6 fatty acids for a robust Atlantic salmon (Salmo salar)

An optimal diet for Atlantic salmon (Salmo salar) should promote a healthy fish that is robust to changes in its environmental conditions and can withstand the handling it will encounter under farming conditions, all while promoting good and rapid growth. The plant ingredients commonly used in aquafeeds do not have an ideal FA composition for salmon. In particular, they are lacking the n-3 fatty acids (FA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are essential nutrients for salmon. Further, they are rich in the n-s6 FA linoleic acid (LA) and the n-9 FA oleic acid (OA), which are not common in the natural diet of salmon. The exact requirement of EPA and DHA for Atlantic salmon is, however, still not known. There are also indications that a higher inclusion of dietary n-6 FA can increase the requirement for EPA and DHA. Many previous trials investigating these nutrients have been short-term, land-based trials where the fish have been shielded from difficult situations. Though such trials can define minimum requirements, the practical requirements need to be determined in a challenging environment. The focus of this thesis has been to investigate the effect of dietary EPA, DHA and n-6 FA on the robustness of Atlantic salmon exposed to challenging environmental conditions. It has been suspected that dietary n-6 can affect the requirement of EPA and DHA, and that it may have an effect on the response to chronic and acute stress. To investigate this, a feeding experiment was conducted with three diets containing equal absolute amounts of n-3 FA and increasing n-6 FA (n-6/n-3 ratios of 1, 2 and 6), as well as a final diet with double absolute n-3 FA content and an n-6/n-3 ratio of 1. This allowed for a separation between effects of ratio and absolute amounts on tissue FA levels. These diets were used in a 13-week growth trial and a 4-week stress trial. In the stress trial, half the fish were exposed to a repeated stressor (hypoxia) three times weekly, while the other half were undisturbed controls. At the end of the experiment, all fish were exposed to a confinement stressor. These trials confirmed that dietary n-6 FA increases the requirement for EPA, but not DHA. Despite equal level of dietary EPA + DHA, an increasing level of dietary n-6 FA (a higher n-6/n-3 ratio) resulted in lower levels of EPA in polar lipids (liver polar lipids, red blood cells, skin phospholipids, brain polar lipids). A higher feed n-6/n-3 ratio increased the level of all n-6 FA (including the longer-chain n-6 FA). However, maintaining a low n-6/n-3 ratio inhibited the increased incorporation of n-6 into polar lipids despite higher dietary absolute levels of n-6 FA. Generally, polar lipids reflected the relative n-6 and n-3 level of the feed, while in neutral lipids the FA composition was more related to the absolute contents. These results indicate a competition between n-3 and n-6 FA for incorporation into polar lipids. When investigating the effect of these diets on the stress response, it was found that all fish appeared phenotypically healthy, and were able to mount an acute stress response. There were hardly any significant effects of the repeated hypoxia stressor, possibly indicating an adaptation. Hepatic production of prostaglandin D2 (PGD2) and leukotriene B4 (LTB4) responded differently to acute stress depending on the feed n-6/n-3 FA ratio, which suggests a dietary impact on the acute stress response. Based on still declining rather than recovering PGD2 levels 24 hours after exposure to the acute stressor, fish fed an n-6/n-3 ratio of 6 recovered more slowly from the stress compared to fish fed a ratio of 1. Furthermore, the n-6/n-3 ratio of 6 resulted in rising levels of LTB4 in the fish liver one hour after acute stress compared to a decline seen in fish fed a ratio of 1. A general increase of the arachidonic acid (ARA) derived prostaglandins PGE2 and PGD2 was further seen in fish fed the high n-6/n-3 ratio. Eicosanoids are highly potent molecules, particularly the ones derived from ARA. Upsetting the balance between their n-3 and n-6 FA precursors, and hence their production, might lead to overly strong responses when salmon are exposed to stressors. A low dietary n-6/n-3 ratio will therefore likely be beneficial for the stress coping ability of salmon. The final study examined how graded levels of EPA and DHA from 10 to 35 g/kg feed affected liver lipid metabolism in salmon kept in open sea cages during a full production cycle. Changes to the hepatic energy metabolism when reducing dietary EPA + DHA were discovered using a metabolomics approach. An inhibition of hepatic β‐oxidation likely occurred in the fish fed the lowest levels of EPA + DHA (10 g/kg), as evidenced by less tricarboxylic acid cycle intermediates originating from β‐oxidation. Additionally, in the low EPA + DHA groups, other pathways providing metabolic energy, such as the pentose phosphate pathway, branched chain amino acid catabolism and creatine metabolism were activated in the liver. Increases in various acylcarnitines in the liver of the same fish, in particular accumulation of 3-hydroxyacrnintines (intermediates in mitochondrial β‐oxidation), supported this and indicated disturbances in the hepatic lipid metabolism. Elevated liver lipids were furthermore observed in fish fed lower levels of EPA and DHA, aligning well with the metabolite data. The study showed that diets containing 10 and 13 g/kg EPA and DHA were insufficient for maintaining good liver metabolic health in Atlantic salmon. However, 35 g/kg dietary EPA and DHA was also significantly better than 16 g/kg, indicating that 16 g/kg might be suboptimal as well.Doktorgradsavhandlin

Heterocalixarenes. Part 3: Bis-oxo-bridged calix[1]cyclicurea[3]arene and calix[1]cyclicurea[1]pyridine[2]arenes. Synthesis, X-Ray crystal structure and conformational analysis

The Friedel-Crafts aroylations of 2- and 4-methylanisole with isophthaloyl dichloride or pyridine-2,6-dicarbonyl dichloride provide respective diones, which on bromination with NBS provide corresponding bisbromomethyl derivatives that undergo simple cyclocondensations with embedded cyclicurea-containing heterocycles, viz. benzimidazol-2(1H)-one, 5-nitrobenzimidazol-2(1H)-one, 5,6-dinitrobenzimidazol-2(1H)-one, uracil and quinazoline-2,4(1H,3H)-dione to form 11 new bis-oxo-bridged heterocalix[4]arenes ( 11-19, 24, 25). The X-ray crystal structure of the 11-benzene complex, 1H-1H COSY spectra and energy-minimization studies assign partial cone conformations to these heterocalix[4]arenes. The variation in the cyclicurea moiety controls the flexibility of these heterocalix[4]arenes

Heterocalixarenes part 4. Synthesis of oxocalix [1] heterocycle [2]-arenes: a unique H-bonding network in calix [1] benzimidazol-2-one [2] arene &#189; H<SUB>2</SUB>O

The Friedel.Crafts aroylation of 2-methylanisole with 3-methylbenzoyl chloride followed by NBS bromination and cyclizations with 1,3-dihydrobenzimidazol-2-one, 1,3-dihydro-5,6-dinitrobenzimidazol-2-one, uracil, 6-methyluracil and quinazoline-2,4(1H,3H)-dione provide respective oxocalix[1]heterocycle[2]arenes 5.9. The X-ray crystal structure (solid) and 1H NMR spectral (solution) studies show them to have by and large inwardly flattened partial cone conformations which vary in torsion angles between the rings. The calix[1]benzimidazol-2-one[2]arene &#189; H2O complex shows a unique array of H-bonds in which three of the four CH and the imide oxygen of the benzimidazol-2-one unit, carbonyl oxygen and water molecule are involved in H-bonding with surrounding calixarene molecules. This heterocalixarene, in contrast to earlier reported benzimidazol-2-one-based calixarenes, does not show heterocyclic &#960;-&#960; stacking

The synthesis and X-Ray structure analysis of an unusual bent anthraquinone based coronand

The phase transfer catalyzed cyclisation of 1,8-dihydroxyanthraquinone with bis(2-bromoethyl) ether provides an unusual bent anthraquinone based coronand

Effect of heavy metals on the survival, growth and development of earthworm Eisenia fetida

The present laboratory study was carried out to determine the effect of the metal contaminated soil on the survival, growth and development of Eisenia fetida. Metal contaminated soil samples were collected from five different sites of Ludhiana city which is an industrial hub of Punjab. Maximum heavy metal concentrations were recorded in soil sample taken from hambran around the Buddha Nullah and minimum concentration of heavy metal from haibowal. The level of heavy metals chromium and nickel (347 ppm and 189 ppm) were higher than permissible limits according to CCME (2001), whereas lead (42.6 ppm) was within permissible limits. Adult E. fetida were exposed to different concentrations of heavy metals in artificial soil for 28 days. Significant effects were observed on growth and reproduction of the tested organisms. There was 100% survival of E. fetida in soil amended with lead, chromium and nickel along with morphological abnormalities such as extrusion of coelomic fluid. It was observed that the worms in the low and high doses of heavy metal treated substrate produced cocoons with a one week and two week delay, respectively, vis-a-vis the control group. Furthermore, the emergence of hatchlings started one week earlier in control than in soil treated with medium and high concentration of metals. It is safely concluded that presence of heavy metal in soils adversely affects the growth, reproduction and development of E. fetida. Results ofthe study indicated that reproduction was more sensitive to higher concentrations of heavy metal contaminated soil than survival or weight change

Application of security technologies in the public websites of banks in Serbia

In this publication, the collected data in the course of a survey are summarized, systemized and analyzed. The survey is conducted in the autumn of 2018 and is focused on the usage of the HTTPS protocol in the public web sites of Serbian banks. The scope of the survey is limited only to the public site of the particular bank and 27 web sites were explored. All of them belong to Serbian banks, which are licensed by the National Bank of Serbia. The HTTPS protocol in the last years is used as the default protocol by many web applications. The study shows that from all 27 Serbian banks licensed by the Serbian National Bank, 81.5% (22 banks) of the surveyed bank's sites are using HTTPS without problems, 11.1% (3 banks) are using HTTPS with some problems and 7,4% (2 banks) are not using HTTPS at all. From banks that are using HTTPS without any problems, the majority - 72.7% (16 banks) use simple Domain Validation (DV), and the rest - 27.2% (6 banks) use Extended Validation (EV) types of certificates. The most popular certification authorities are Thawte with share of 27.2% (6 banks), Go Daddy Secure Certificate Authority and GeoTrust - each with share of 18.1% (4 banks), cPanel Inc. Certification Authority - 13.6% (3 banks), and etc. One bank uses free certificate from Let's Encrypt Authority X3. The validity period varies from 3 months (typically issued from cPanel and Let's Encrypt) to 3 years (typically issued from Go Daddy). Only 7.4% (2 banks) of all Serbian banks are using the latest HTTP/2 protocol