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الجنس والمخدرات والقمار والشوكولاتة : كتاب عملي للتغلب على حالات الإدمان
يتناول كتاب (الجنس والمخدرات والقمار والشوكولاتة : كتاب عملي للتغلب على حالات الإدمان) والذي قام بتأليفه (الدكتور إيه توماس هورفاث) في حوالي (235) صفحة من القطع المتوسط موضوع (موجزات إرشادية للوقاية من إدمان المخدرات والسلوك القهري) وهو كتاب صريح ومباشر وهو ذو أسس علمية وبديل عملي عن برامج الإثنتي عشرة خطوة .. كما أنه كتاب إرشادي للمساعدة الذاتية يتضمن تفاصيل مستفيضة وشروحا ونصائح حكيمة عن علاج الإدمان، البدائل العلاجية واختبارها، التغلب على مشكلات إدمان الكحول.
BOOK
The impact of ageing, socio-economic differences and the evolution of morbidity on future health expenditure – a dynamic microsimulation
Background
Population ageing is associated with rising healthcare expenditure. To inform policy and adapt health systems accordingly, a detailed quantitative analysis of the different components of ageing and other factors that influence cost dynamics is needed.
Methods
We use dynamic microsimulation to project healthcare expenditure in Austria and disentangle the effects of changes in longevity, population age-structure, healthy life years and socio-economic health disparities. By combining price weights for healthcare services with information on healthcare consumption from the Austrian Health Interview Survey, we construct average cost profiles by gender, age, and education. These profiles, aligned with the System of Health Accounts, are integrated into the
microDEMS
model, along with official population projections, to estimate expenditure scenarios until 2060. We examine the relationship between rising life expectancy and changes in healthy life years and assess the potential impact of closing the gap in costs currently observed between education groups. Total and per-capita cost trajectories are derived and evaluated against two indicators for the size of the labor force to assess economic implications.
Results
In all scenarios, demographic ageing increases the financial burden on the economically active population, even with morbidity compression. Nearly two-thirds of the projected cost increase stems from declining mortality, while one-third results from age-structure changes. Per-capita costs rise by 26% under a morbidity expansion scenario but could decrease by 5% if lower mortality is accompanied by an extension of healthy life years and a reduction in socio-economic health disparities. In economic terms, costs per working-age person increase by 12% to 48%, depending on the scenario. When adjusting for labor force expansion and the associated economic benefits, the increase ranges between 5% and 39%.
Conclusions
Rising healthcare expenditure poses a major challenge in an ageing society. However, policies that extend healthy life years and reduce socio-economic disparities offer viable strategies to significantly mitigate the economic impact of ageing.
Journal Article
Interrogation of the mammalian gut–brain axis using LC–MS/MS-based targeted metabolomics with in vitro bacterial and organoid cultures and in vivo gnotobiotic mouse models
Interest in the communication between the gastrointestinal tract and central nervous system, known as the gut–brain axis, has prompted the development of quantitative analytical platforms to analyze microbe- and host-derived signals. This protocol enables investigations into connections between microbial colonization and intestinal and brain neurotransmitters and contains strategies for the comprehensive evaluation of metabolites in in vitro (organoids) and in vivo mouse model systems. Here we present an optimized workflow that includes procedures for preparing these gut–brain axis model systems: (stage 1) growth of microbes in defined media; (stage 2) microinjection of intestinal organoids; and (stage 3) generation of animal models including germ-free (no microbes), specific-pathogen-free (complete gut microbiota) and specific-pathogen-free re-conventionalized (germ-free mice associated with a complete gut microbiota from a specific-pathogen-free mouse), and
Bifidobacterium dentium
and
Bacteroides ovatus
mono-associated mice (germ-free mice colonized with a single gut microbe). We describe targeted liquid chromatography–tandem mass spectrometry-based metabolomics methods for analyzing microbially derived short-chain fatty acids and neurotransmitters from these samples. Unlike other protocols that commonly examine only stool samples, this protocol includes bacterial cultures, organoid cultures and in vivo samples, in addition to monitoring the metabolite content of stool samples. The incorporation of three experimental models (microbes, organoids and animals) enhances the impact of this protocol. The protocol requires 3 weeks of murine colonization with microbes and ~1–2 weeks for liquid chromatography–tandem mass spectrometry-based instrumental and quantitative analysis, and sample post-processing and normalization.
Targeted liquid chromatography–tandem mass spectrometry-based metabolomics using in vitro (organoids) and in vivo (gnotobiotic mice colonized with mono- or multi-species bacterial cultures) systems examines the role of specific microbially driven pathways of the mammalian gut–brain axis.
Journal Article
The Impact of Health and Education on Labor Force Participation in Aging Societies: Projections for the United States and Germany from Dynamic Microsimulations
We project the labor force in the United States to 2060 and contrast the outcomes with comparative projections for Germany. In both countries, the population will age, but the demographic dynamics are fundamentally different. According to our dynamic microsimulations, the labor force in the U.S. will increase by 17 percent between 2020 and 2060 (about 29 million workers) despite population aging. In contrast, the labor force in Germany will decline by 11 percent (about 4.5 million workers). Our baseline projections indicate that an expansion of education will increase the labor force by about 3 million persons in the United States and about half a million persons in Germany by 2060. In several what-if scenarios, we examine the effects of further expanding education and of removing health barriers on labor force participation. Higher educational attainment among those with currently low education has the largest impact on labor force participation, relative to the additional years of schooling. However, health improvements and the labor market integration of people with health limitations suggest a larger increase in labor force participation rates. Using Sweden as a benchmark, we show that reducing the health participation gap would increase the U.S. labor force by as much as 13 million people in 2060 (+6.8 percent compared to our baseline).
Journal Article
Characterizing arginine, ornithine, and putrescine pathways in enteric pathobionts
Arginine‐ornithine metabolism plays a crucial role in bacterial homeostasis, as evidenced by numerous studies. However, the utilization of arginine and the downstream products of its metabolism remain undefined in various gut bacteria. To bridge this knowledge gap, we employed genomic screening to pinpoint relevant metabolic targets. We also devised a targeted liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) metabolomics method to measure the levels of arginine, its upstream precursors, and downstream products in cell‐free conditioned media from enteric pathobionts, including Escherichia coli, Klebsiella aerogenes, K. pneumoniae, Pseudomonas fluorescens, Acinetobacter baumannii, Streptococcus agalactiae, Staphylococcus epidermidis, S. aureus, and Enterococcus faecalis. Our findings revealed that all selected bacterial strains consumed glutamine, glutamate, and arginine, and produced citrulline, ornithine, and GABA in our chemically defined medium. Additionally, E. coli, K. pneumoniae, K. aerogenes, and P. fluorescens were found to convert arginine to agmatine and produce putrescine. Interestingly, arginine supplementation promoted biofilm formation in K. pneumoniae, while ornithine supplementation enhanced biofilm formation in S. epidermidis. These findings offer a comprehensive insight into arginine‐ornithine metabolism in enteric pathobionts. The amino acid L‐arginine is converted by bacteria into a variety of downstream metabolites, including citrulline, agmatine, ornithine, putrescine, and gamma‐aminobutyric acid (GABA). Our study shows that both Gram‐negative bacteria (Escherichia coli, Klebsiella pneumoniae, Klebsiella aerogenes, Pseudomonas fluorescens, and Acinetobacter baumannii) and Gram‐positive bacteria (Streptococcus agalactiae, Staphylococcus epidermidis, Staphylococcus aureus, and Enterococcus faecalis) consume arginine, glutamine, and glutamate, and generate citrulline, ornithine, and GABA. This suggests that these pathways are conserved and essential within gut bacteria. We also found that Escherichia coli, Klebsiella pneumoniae, Klebsiella aerogenes, and Pseudomonas fluorescens generate the arginine intermediate agmatine and produce the polyamine putrescine. These findings indicate that arginine is a crucial amino acid for gut bacteria.
Journal Article
Discovery of phosphorylated lantibiotics with proimmune activity that regulate the oral microbiome
Lantibiotics are ribosomally synthesized and posttranslationally modified peptides (RiPPs) that are produced by bacteria. Interest in this group of natural products is increasing rapidly as alternatives to conventional antibiotics. Some human microbiome–derived commensals produce lantibiotics to impair pathogens’ colonization and promote healthy microbiomes. Streptococcus salivarius is one of the first commensal microbes to colonize the human oral cavity and gastrointestinal tract, and its biosynthesis of RiPPs, called salivaricins, has been shown to inhibit the growth of oral pathogens. Herein, we report on a phosphorylated class of three related RiPPs, collectively referred to as salivaricin 10, that exhibit proimmune activity and targeted antimicrobial properties against known oral pathogens and multispecies biofilms. Strikingly, the immunomodulatory activities observed include upregulation of neutrophil-mediated phagocytosis, promotion of antiinflammatory M2 macrophage polarization, and stimulation of neutrophil chemotaxis—these activities have been attributed to the phosphorylation site identified on the N-terminal region of the peptides. Salivaricin 10 peptides were determined to be produced by S. salivarius strains found in healthy human subjects, and their dual bactericidal/antibiofilm and immunoregulatory activity may provide new means to effectively target infectious pathogens while maintaining important oral microbiota.
Journal Article
Neurotransmitter Profiles Are Altered in the Gut and Brain of Mice Mono-Associated with Bifidobacterium dentium
Background: Accumulating evidence indicates that the gut microbiota can synthesize neurotransmitters as well as impact host-derived neurotransmitter levels. In the past, it has been challenging to decipher which microbes influence neurotransmitters due to the complexity of the gut microbiota. Methods: To address whether a single microbe, Bifidobacterium dentium, could regulate important neurotransmitters, we examined Bifidobacteria genomes and explored neurotransmitter pathways in secreted cell-free supernatant using LC-MS/MS. To determine if B. dentium could impact neurotransmitters in vivo, we mono-associated germ-free mice with B. dentium ATCC 27678 and examined fecal and brain neurotransmitter concentrations. Results: We found that B. dentium possessed the enzymatic machinery to generate γ-aminobutyric acid (GABA) from glutamate, glutamine, and succinate. Consistent with the genome analysis, we found that B. dentium secreted GABA in a fully defined microbial media and elevated fecal GABA in B. dentium mono-associated mice compared to germ-free controls. We also examined the tyrosine/dopamine pathway and found that B. dentium could synthesize tyrosine, but could not generate L-dopa, dopamine, norepinephrine, or epinephrine. In vivo, we found that B. dentium mono-associated mice had elevated levels of tyrosine in the feces and brain. Conclusions: These data indicate that B. dentium can contribute to in vivo neurotransmitter regulation.
Journal Article
The metabolic profile of Bifidobacterium dentium reflects its status as a human gut commensal
Background
Bifidobacteria are commensal microbes of the mammalian gastrointestinal tract. In this study, we aimed to identify the intestinal colonization mechanisms and key metabolic pathways implemented by
Bifidobacterium dentium
.
Results
B. dentium
displayed acid resistance, with high viability over a pH range from 4 to 7; findings that correlated to the expression of Na+/H+ antiporters within the
B. dentium
genome.
B. dentium
was found to adhere to human MUC2+ mucus and harbor mucin-binding proteins. Using microbial phenotyping microarrays and fully-defined media, we demonstrated that in the absence of glucose,
B. dentium
could metabolize a variety of nutrient sources. Many of these nutrient sources were plant-based, suggesting that
B. dentium
can consume dietary substances. In contrast to other bifidobacteria,
B. dentium
was largely unable to grow on compounds found in human mucus; a finding that was supported by its glycosyl hydrolase (GH) profile. Of the proteins identified in
B. dentium
by proteomic analysis, a large cohort of proteins were associated with diverse metabolic pathways, indicating metabolic plasticity which supports colonization of the dynamic gastrointestinal environment.
Conclusions
Taken together, we conclude that
B. dentium
is well adapted for commensalism in the gastrointestinal tract.
Journal Article
Life course heterogeneity and the future labour force – A dynamic microsimulation analysis for Austria
Using Austria as a case study, this paper demonstrates how capturing life course heterogeneity improves the accuracy and policy relevance of socio-demographic projections, and how considering this population heterogeneity impacts labour force dynamics and economic dependency ratios. We introduce and apply the microsimulation model microDEMS, focusing on education, migration background, health and labour market participation. Using administrative data, the model ensures longitudinal consistency of labour market careers, including insurance periods, and considers pension rules and reforms. Despite its level of detail, microDEMS is consistent with official demographic projections. To assess sensitivity, we create alternative scenarios that illustrate how different factors affect future labour force dynamics. The main result of our simulation analysis is the quantification of substantial mitigating effects of improvements in education and already adopted changes in pension legislation, which together reduce the impact of ageing on the economic dependency ratio by 55%.
Journal Article