9 research outputs found
The Effect of ISBT-Bowen Therapy in the Treatment of Myofascial Neck Pain—a Randomized, Single-Blinded Clinical Trial
No full textBackground: Myofascial pain syndrome (MPS) is the most common diagnosis in patient presenting with chronic nonspecific neck pain. It affects people’s work performance, productivity, and quality of life. To date, there is little research evaluating the effectiveness of non-invasive techniques, such as ISBT-Bowen Therapy in managing neck MPS.
Objectives: To investigate the effectiveness of Bowen therapy in managing myofascial pain syndrome with symptoms lasting for more than six weeks. The study will also examine the long-term effect of ISBT-Bowen Therapy on functional enhancement, quality of life, and physical and mental well-being.
Methods: This is a prospective, single-blinded randomized controlled trial (RCT). A total of 90 myofascial neck pain patients were recruited and randomized to receive 8 sessions of ISBT-Bowen Therapy over a 12-week period (n = 45) or to continue their usual conventional treatment (n = 45). Pressure pain threshold (PPT), cervical range of motion (CROM), numerical rating pain scores, Neck Disability Index (NDI), SF-12 Health Survey (SF-12) Version 2, Generalized Anxiety Disorder 7-item (GAD7), and Patient Health Questionnaire (PHQ9) were measured at baseline, 12 weeks, and 24 weeks after baseline.
Results: When compared with the control group, PPT significantly increased after ISBT-Bowen Therapy at 12 and 24 weeks. CROM on flexion, lateral flexion, and rotation were greatly improved at 12 weeks after Bowen therapy, and maintained at 24 weeks, except left lateral flexion. NDI, GAD7, and PHQ9 were all reduced after Bowen Therapy at both 12 and 24 weeks. Both Physical and Mental Component Summary scores of SF-12 were improved after Bowen therapy at 12 and 24 weeks.
Conclusions: This study confirmed the efficacy of ISBT-Bowen Therapy for patients with MPS. It alleviates pain, improves functional outcomes, enhances quality of life, and relieves mood symptoms
Reservoir computing with output feedback
No full textReinhart RF. Reservoir computing with output feedback. Bielefeld: Bielefeld University; 2011.A dynamical system approach to forward and inverse modeling is proposed. Forward and inverse models are trained in associative recurrent neural networks that are based on non-linear random projections. Feedback of estimated outputs into such reservoir networks is a key ingredient in the context of bidirectional association but entails the problem of error amplification. Robust training of reservoir networks with output feedback is achieved by a novel one-shot learning and regularization method for input-driven recurrent neural networks. It is shown that output feedback enables the implementation of ambiguous inverse models by means of multi-stable dynamics. The proposed methodology is applied to movement generation of robotic manipulators in a feedforward-feedback control framework
The effect of glucose on cardiac AMP-activated protein kinase
No full textAMP-activated protein kinase (AMPK) serves as an energy-sensing protein that is activated by a variety of metabolic stresses. Recent studies suggest that AMPK is also regulated by hormones and by nutrients such as glucose and fatty acids. In skeletal muscle it was previously shown that AMPK activity was decreased with increasing glucose concentration. In the present study both the activity and the Threonine-172 phosphorylation of AMPK in incubated rat ventricular cardiac myocytes were found to be decreased by increasing glucose in the presence and absence of palmitate. Glucose also caused a decrease in the AMPK-driven phosphorylation of acetyl-CoA carboxylase. Measurements of the myocyte contents of ATP, ADP, AMP and glycogen showed that the effect of glucose on AMPK activity could not be secondary to changes in the levels of these metabolites. The decrease in AMPK activity with glucose was additive to and distinct from the effect of insulin which is mediated through protein kinase B (PKB). Increasing glucose concentration had no effect on the phosphorylation of Threonine-308 and Serine-473 in PKB. AICAR, a pharmacological activator of AMPK, had no effect on the ability of glucose to inactivate AMPK. The myocyte content of the pentose phosphate pathway (PPP) metabolite xylulose 5-phosphate (Xu5P), a known allosteric activator of PP2A, was increased with increasing glucose concentration such that AMPK activity was inversely related to Xu5P content. The glucose 6-phosphate dehydrogenase inhibitor diehydroepiandeosterone (DHA) and thiamine, the precursor of the coenzyme for transketolase, both increased AMPK activity whereas the NADPH oxidant phenazine methosulphate (PMS) decreased AMPK activity. DHA and PMS respectively decreased and increased flux through the PPP. The findings suggest that inactivation of AMPK by glucose may be mediated by the activity of the PPP which sets the level of Xu5P. Two other findings were also made during the course of this project. First, the activity of phosphofructokinase-2 (PFK-2) in the perfused heart was previously shown to be activated through phosphorylation by AMPK. It was therefore expected that increasing glucose concentration would decrease myocyte PFK-2 activity. However PFK-2 activity was found to be increased by glucose. Second, the phosphorylation of Threonine-308 in PKB in response to insulin was appreciably increased in the presence of AICAR suggesting that there may be crosstalk between AMPK and the insulin signalling pathway at the level of PKB
Water acidification: effects on the macroalgal community
No full textRecent researches, performed in a naturally acidified site (Castello Aragonese d’Ischia - Gulf of Naples, Italy) where volcanic carbon dioxide vents cause long-term changes in seawater carbonate chemistry, lowering the pH from 8.17 down to 6.57, reveal winners and losers within the benthic community. In the same site, we chose to address the impact of ocean acidification on the algal community with an integrated approach by means of ecological, physiological and molecular tools.
Qualitative and quantitative changes in algal composition have been detected. Results showed a less structured community at low pH, characterized by few dominant species and the lack of calcareous taxa.
Due to their different tolerance to pH variations, three target species (Sargassum vulgare, Dictyota dichotoma and Jania rubens) have been selected to carry out transplant experiments in order to detect short term stress signals. Variations in fluorometry-derived parameters of the photosynthetic performance of these species were detected in situ at different pH conditions by means of a Diving-PAM.
In order to understand if the chronic lowering of pH of this site has promoted any local adaptations (morphological and/or genetic), the Dictyota complex species have been selected.
Results indicate that our integrated approach is the key factor leading to understand how these changes can drive deteriorations in the structure and function of algal assemblages under the effects of water acidification
Discovery of antiprotozoal compounds from medicinal plants
No full textTropical parasitic diseases such as malaria, human African trypanosomiasis, chagas disease, and leishmaniasis affect hundreds of millions of people worldwide and have devastating consequences. Current drugs available to treat these diseases have serious drawbacks. New drugs are urgently needed.
Natural products (NPs) play a dominant role in drug discovery for the treatment of human diseases. Particularly, quinine and artemisinin have their origin in nature and have inspired successful drugs for malaria treatment.
In a medium throughput screening, a total of 507 extracts from South African plants were assayed for their antiprotozoal activity against Plasmodium falciparum, Trypanosoma brucei rhodesiense, Trypanosoma cruzi and Leishmania donovani. Extracts from Abrus precatorius L. ssp. africanus Verdc. (Fabaceae) and Drypetes gerrardii Hutch. var. gerrardii (Putranjivaceae) inhibited at least one of the parasites at a test concentration considered relevant. With the aim of identifying the compounds responsible for these activities, a HPLC-based activity profiling approach followed by dereplication was applied. Targeted isolation of promising compounds was achieved by a combination of chromatography techniques. Structure elucidation was achieved by HR-ESI-MS and NMR (1H, 13C, COSY, HMBC, HSQC, and NOESY spectroscopy). Absolute configuration was determined by comparison of electronic circular dichroism (ECD) spectra with calculated ECD data.
HPLC-based activity profiling of A. precatorius allowed the identification of abruquinones, as responsible for the trypanocidal activity of the crude extract. A total of ten abruquinones were isolated. Among these were five new compounds. Abruquinone B, I, A, D, K, and L showed remarkable inhibition (0.16 ± 0.060, 0.28 ± 0.051, 0.02 ± 0.003, 0.01 ± 0.001, 0.11 ± 0.053, and 0.02 ± 0.053, respectively) and notable selectivity, expressed as selectivity indices (SIs) which were calculated from cytotoxicity data in L-6 cells (51, 74, 1379, 668, 508, and 374, respectively). These results warrant in vivo assessment of abruquinones.
Abruquinones are promising hits due to their strong and selective in vitro inhibition of T. b. rhodesiense, their good compliance with Lipinski’s “rule-of-5” and other molecular properties, as well as their predicted low/moderate toxic potential.
Two different extracts of D. gerrardii showed antiprotozoal activity, and the active constituents were tracked and isolated by HPLC-based activity profiling. The CH2Cl2/MeOH (1:1) stems extract inhibited L. donovani and P. falciparum. The major compound, a new phenanthrenone, showed good in vitro activity (IC50 of 0.9 ? 0.3 mM) and selectivity (SI of 68) against P. falciparum. Based on these promising results, in-vivo studies were conducted. However, the compound was not able to reduce parasitemia in the P. berghei mouse model. A phenanthrenone heterodimer was also isolated and showed in vitro antiplasmodial activity (IC50 of 2.04 ? 0.15 mM and SI of 31). Furthermore, the CH2Cl2/MeOH (1:1) leaves extract displayed trypanocidal properties, and the known saponin putranoside A was isolated and tested against T. b. rhodesiense, (IC50 of 18.0 ? 3.8 mM and a SI of 4).
The phenanthrenone was the most active and selective in vitro inhibitor of P. falciparum, but showed no inhibition in vivo against P. berghei. However, the compound fulfilled Lipinski’s “rule-of-5” and other molecular properties, which indicates a potential to meet requirements of an ideal antimalarial drug such as, oral bioavailability and blood-brain barrier permeability. According to Medicines for Malaria Venture compound progressing criteria, the phenanthrenone complies with some of the features of a validated hit such as sufficient activity against P. falciparum in vitro (? 1 ?M).
Additionally, as part of a project aimed at investigating antiprotozoal European plants Chrysanthemum cynerariifolium (Trevir.) Vis. (Asteraceae), Laurus nobilis L. (Lauraceae), and Eupatorium cannabinum L. (Asteraceae) were studied. A hexane extract of C. cynerariifolium showed promising activity against P. falciparum. Pyrethrins (irregular monoterpenes) were the metabolites responsible for the antiplasmodial activities. Particularly, pyrethrin II and jasmolin II inhibited P. falciparum (IC50 4.0 ? 1.1 ?M and 5.0 ? 0.4 ?M, respectively and SI of 24 and 6, respectively) in vitro. Synthetic pyrethroids were also tested, but they did not show activity.
Finally, as a contribution to the structure activity relationship study of sesquiterpene lactones showing activity against T. b. rhodesiense, costunolide and zaluzanin D were isolated from Laurus nobilis L. (Lauraceae) and eupatoriopicrin from Eupatorium cannabinum L. (Asteraceae). Germacrolides, i.e. costunolide and eupatoriopicrin, showed a higher inhibition (IC50 of 1.3 ? 0.4 mM and 1.2 ± 0.2 mM, respectively) on the protozoon, than the guaianolide zaluzanin D (IC50 of 10.8 mM).
In brief, a total of 22 secondary metabolites were isolated from five species. Among them, seven new compounds were discovered. These compounds belong to the structural classes of isoflavonoids, phenanthrenones, and terpenes such as, sesquiterpene lactones, irregular monoterpenes and triterpenoid saponins. Most of them (15 compounds) exhibited in vitro antiprotozoal activity. The most promising compounds were the abruquinones and the phenanthrenone, which strongly and selectively inhibited T. b. rhodesiense and P. falciparum, respectively. Abruquinones and the phenanthrenone are drug-like compounds with a calculated toxic potential ranging from low to moderate.
ZUSAMMENFASSUNG
Tropische parasitäre Krankheiten wie Malaria, afrikanische Trypanosomiasis (Schlafkrankheit), Chagas-Krankheit und Leishmaniose betreffen Hunderte von Millionen Menschen weltweit und haben verheerenden Folgen. Aktuelle Medikamente, die zur Behandlung dieser Krankheiten zur Verfügung stehen, haben gravierende Nachteile. Neue Medikamente werden dringend benötigt.
Naturstoffe (NP) spielen eine dominierende Rolle in der Wirkstoffforschung für die Behandlung von menschlichen Erkrankungen. So haben Chinin und Artemisin ihren Ursprung in der Natur und führten zu erfolgreichen Medikamenten zur Malariabehandlung.
In einem mittleren Durchsatz-Screening wurden insgesamt 507 Extrakte von südafrikanischen Pflanzen auf ihre Aktivität gegen Protozoen - Plasmodium falciparum, Trypanosoma brucei rhodesiense, Trypanosoma cruzi und Leishmania donovani - getestet. Extrakte von Abrus precatorius L. ssp. africanus Verdc. (Fabaceae) und Drypetes gerrardii Hutch. var. gerrardii (Putranjivaceae) haben mindestens einen der Parasiten in einer als relevant bezeichneten Testkonzentration gehemmt.
Mit dem Ziel die für diese Aktivitäten verantwortlichen Verbindungen zu identifizieren wurde ein Ansatz bestehend aus HPLC-basiertes Aktivitäts-Profiling gefolgt von Dereplikation verwendet. Gezielte Isolierung der vielversprechenden Verbindungen erfolgte durch eine Kombination von Chromatographie-Techniken. Die Strukturaufklärung wurde durch HR-ESI-MS und NMR (1H, 13C, COSY, HMBC, HSQC, und NOESY Spektroskopie) durchgeführt. Die absolute Konfiguration wurde durch den Vergleich der elektronischen Zirkulardichroismus-(ECD)-Spektren mit berechneten ECD-Daten bestimmt.
HPLC-basiertes Aktivitäts-Profiling von A. precatorius ermöglichte die Identifizierung von Abruquinonen, als verantwortliche Substanzen für die trypanozide Aktivität des Rohextrakts. Es wurden insgesamt 10 Abruquinone isoliert, darunter fünf neue Verbindungen. Abruquinone B, I, A, D, K und L zeigten bemerkenswerte Hemmung (0.16 ± 0.060, 0.28 ± 0.051, 0.02 ± 0.003, 0.01 ± 0.001, 0.11 ± 0.053, und 0.02 ± 0.053) und beachtenswerte Selektivität, wiedergegeben als Selektivitätsindizes (SIs) die aus der Zytotoxizität in L-6 Zellen (51, 74, 1379, 668, 508, und 374) ermittelt wurden.
Wegen ihrer starken und selektiven in vitro Hemmung von T. b. rhodesiense, ihrer guten Übereinstimmung mit Lipinski’s „5er Regel“ und anderen molekularen Eigenschaften, sowie ihrem niederen/mässigen toxischen Potenzial sind Abruquinone vielversprechende Hits. Deshalb sind weitere Studien notwendig um botanische oder chemische Quellen sicherzustellen und die in-vivo Wirksamkeit dieser Verbindungen zu bestimmen.
Zwei verschiedene Extrakte von D. gerrardii zeigten Aktivität gegen Protozoen. Die aktiven Bestandteile wurden mit Hilfe vom HPLC-basiertem Aktivitäts-Profiling identifiziert und isoliert. Der CH2Cl2/MeOH (1:1) Extrakt aus den Stängeln hemmte L. donovani und P. falciparum. Die Hauptverbindung, ein neues Phenanthrenon, zeigte gute in vitro Aktivität (IC50 von 0.9 ? 0.3 mM) und Selektivität (SI von 68) gegen P. falciparum. Basierend auf diesen vielversprechenden Resultaten wurden in vivo Studien durchgeführt. Allerdings war diese Verbindung nicht in der Lage die Parasitenbelastung im P. berghei Mausmodell zu reduzieren. Es wurde ebenfalls ein Phenanthrenon-Heterodimer isoliert, der in vitro Aktivität gegen Plasmodien (IC50 von 2.04 ? 0.15 mM und SI von 31) aufwies. Ausserdem zeigte der CH2Cl2/MeOH (1:1) Blattextrakt ausgewiesene trypanozidale Eigenschaften. Aus diesem Extrakt wurde das bekannte Saponin Putranoside A isoliert und gegen T. b. rhodesiense, (IC50 von 18.0 ? 3.8 mM und SI von 4) getestet.
Das Phenanthrenon war der aktivste und selektivste in vitro Inhibitor von P. falciparum, zeigte jedoch keine Hemmung in vivo gegen P. berghei. Die Verbindung erfüllte jedoch Lipinski’s „5er Regel“ und andere molekulare Eigenschaften, wie orale Bioverfügbarkeit und Durchlässigkeit der Blut-Hirn-Schranke, was ein mögliches Potenzial aufzeigt den Anforderungen eines idealen Antimalariawirkstoffs gerecht zu werden. Nach „Medicines for Malaria Venture“-Kriterien für die weitere Entwicklung eines Wirkstoffs erfüllt das Phenanthrenon einige der Merkmale eines validierten Hits wie ausreichende in vitro Aktivität gegen P. falciparum (? 1 ?M).
Als weiterer Teil des Projekts wurde die Wirkung von europäischen Heilpflanzen Chrysanthemum cynerariifolium (Trevir.) Vis. (Asteraceae), Laurus nobilis L. (Lauraceae), und Eupatorium cannabinum L. (Asteraceae) gegen Protozoen studiert. Ein Hexan-Extrakt von C. cynerariifolium zeigte vielversprechende Aktivität gegen P. falciparum. Phyrethrine (unregelmässige Monoterpene) waren die Inhaltsstoffe verantwortlich für die antiplasmodiale Aktivität. Besonders Pyrethrin II und Jasmolin II hemmten P. falciparum (IC50 4.0 ? 1.1 ?M und 5.0 ? 0.4 ?M, und SI von 24 und 6) in vitro. Es wurden auch synthetische Pyrethroide getestet, sie zeigten aber keine Aktivität.
Schliesslich, als Beitrag zu den Struktur-Aktivitätsuntersuchungen von Sesquiterpenlactonen mit Aktivität gegen T. b. rhodesiense, wurden Costunolid und Zaluzanin D aus Laurus nobilis L. (Lauraceae) und Eupatoriopicrin aus Eupatorium cannabinum L. (Asteraceae) isoliert. Germacrolides, d.h. Costunolid und Eupatoriopicrin, zeigten eine höhere Hemmung (IC50 von 1.3 ? 0.4 mM und 1.2 ± 0.2 mM) auf Protozoen als das Guaianolid Zaluzanin D (IC50 von 10.8 mM).
Es wurden insgesamt 22 Sekundärmetaboliten aus fünf Arten isoliert, darunter sieben neue Verbindungen. Diese Substanzen gehören zu den Strukturklassen der Isoflavonoide, Phenanthrenone und Terpene einschliesslich Sesquiterpenelactone, unregelmässige Monoterpene und Triterpenoidsaponine. Die meisten von ihnen (15 Verbindungen) zeigten in vitro Aktivität gegen Protozoen. Die vielversprechendsten Verbindungen waren die Abruquinone und das Phenanthrenon, die starke und selektive Hemmung gegen T. b. rhodesiense und P. falciparum zeigten. Abruquinone und das Phenanthrenon sind drug-like Verbindungen mit einem rechnerischen toxischen Potential von gering bis mässig
Metabolic consequences of neuronal mitochondrial fission ablation
No full textDynamin-related protein 1 (Drp1), the main mammalian mediator of mitochondrial fission, has an especially important role in neuronal development, such that its deletion gives rise to pre- or perinatal lethality. However, less is known about the need for Drp1 in adult neurons; this is relevant because inhibition of Drp1 could prevent pre-apoptotic mitochondrial fragmentation, and therefore be neuroprotective.
In our mouse model, inducible Drp1 ablation in the forebrain of adult mice leads to swollen, perinuclearly aggregated mitochondria and to impaired synaptic transmission. Of note, ablated mice also develop a complex and ultimately lethal catabolic phenotype, marked by weight loss, increased lipolysis and elevated corticosterone. We traced this back to the activation of the integrated stress response in Drp1-ablated brain regions, culminating in the ectopic induction of metabolic cytokine Fgf21. Fgf21 is normally produced in liver, fat and muscle tissue in response to fasting or exercise, and no reports exist of it being produced in the brain. This “mitokine” increases insulin sensitivity and stimulates corticosterone production via receptors in the hypothalamus, thus explaining essential aspects of the catabolic phenotype.
This work has implications not only for mitochondrial biology but also for the understanding of the central regulation of systemic metabolism
Diminishing benefits of urban living for children and adolescents’ growth and development
No full textOptimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified. © 2023, The Author(s)
'The New Generation: Chinese Childhoods'
No full textBased on a data set of 72 semi-structured interviews, undertaken with 12 British Chinese families, this PhD sets out to explore the nature of the childhood experience
within contemporary British Chinese households. By speaking to parents and children of each family using repeat interviews over a nine-month period, accounts of family
life and their relationships with one another can be revealed from both generational perspectives.
From this research, there appears to be a similarity between the practices of past and contemporary British Chinese households, which also coincides with accounts from
pre-existing academic literature. Research findings suggest that Chinese parents (regardless of backgrounds and length of UK residency), not only identify themselves as being Chinese, but also hold strong attachments to 'traditional' Chinese values and norms. For some British Chinese families this causes domestic issues and problems between parents and their more Westernised offspring.
However in comparison to the past, some parents alter and modify their Chinese cultural beliefs which then affect their child-rearing methods, intimacy levels and
opportunities for the child's agency. Reasons for this include the parent's own childhood experience, parent's exposure and acceptance of Western practices, as well
as empathy for their child's experience of being a British Chinese citizen. External circumstances such as the social setting and surroundings, the actions of the child as
well as the parent-child relationship itself also influence household relations and operations.
As such, cultural factors alone are not sufficient in explaining and investigating British Chinese families. Instead contemporary British Chinese parenting approaches,
parent-child intimacy levels and children's agency should be seen as an interactive and reciprocal process, that are created by and contingent upon practices within and
outside of the home. By highlighting the many levels to which British Chinese families play out their lives and how members make sense of their relationships and behaviours, this study expands on the current literature that portrays cultural norms as the main explanatory factor for British Chinese household functioning
