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Citation Information : Acta Neurobiologiae Experimentalis. Volume 78, Issue 2, Pages 69-81, DOI: https://doi.org/10.21307/ane-2018-008
License : (CC-BY-4.0)
Received Date : 01-February-2018 / Accepted: 17-April-2018 / Published Online: 22-August-2018
The purpose of this review is to summarize current knowledge about the gut microbiota in neuropsychiatric disorders. It is estimated that the human gut is colonized by up to 1018 microorganisms, mostly anaerobic bacteria. The gut microbiome is responsible for multiple functions, e.g. tightness of the intestine barrier, digestion and absorption. The correlation between gut dysbiosis and development of psychiatric, autoimmune and allergic diseases as well as bidirectional communication between brain and gut microflora have been shown. Recent findings suggest that specific bacteria can be involved in the development of clinical conditions, such as Autism Spectrum Disorders, depression and schizophrenia, and microbiota may be a target for therapeutic intervention providing novel treatment strategies.
The gut microbiota is composed of thousands of bacteria species weighting together up to 2 kg (Thomas et al. 2015). It is estimated that the human gut is occupied with up to 1018 microorganisms: bacteria (1014, mostly anaerobic), viruses, yeasts, and fungi (Turroni et al. 2008), some of them are unculturable or uncharacterized (Turroni et al. 2008). The intestinal microbiome contains approximately 150 times more unique genes than the human genome (Qin et al. 2010) and the intestinal microflora represents over 200,000 to 1,000,000 bacterial genes (Thomas et al. 2015). The microbiota can be described as metabolic ‘organ’ representing functions that humans have not evolved on their own (Backhed et al. 2004, Bocci 1992). It can communicate with the host, repair itself through self-replication and perform a lot of functions: consuming, mediating chemical transformations, storing and redistributing energy (Backhed et al. 2005).
Microbiota represent an important protection system of the gastrointestinal (GI) tract against harmful pathogens and external factors (Mangiola et al. 2016). Bacteria living in the human intestine achieve the highest documented cell concentration for any ecosystem, 1011-1012 per mL (Hu et al. 2016, Hugenholtz et al. 1998). The most common phyla in the small intestine are Firmicutes and Bacteroidetes, whereas Proteobacteria, Actinobacteria, Fusobacteria, Archea and Verrucomicrobia are represented in smaller quantities (Grenham et al. 2011, Sartor 2008).
The relationship between human and gut microbiota was described as ‘commensal’ (one partner benefits when another is unaffected), which shows that our knowledge is insufficient (Backhed et al. 2005). The gut microbiota is responsible for maturation of the immune system (Kau et al. 2011) in particular of GALT (gut-associated lymphoid tissue) through stimulation of local and systemic immune responses (Nell et al. 2010). The continuous stimulation of the immune system by intestinal bacteria generates a “low-grade physiological inflammation”, which is a rapid and effective defence against pathogens (Fond et al. 2015, Rakoff-Nahoum et al. 2004). The microbiota communicates with the immune system and vice versa (Elson and Alexander 2015) thus dysbiosis defined as shift of microbial composition and beneficial functions (Fond et al. 2015) can result in immune-mediated inflammatory disorders, such as celiac disease (Elson and Alexander 2015).
Microflora is responsible for digestion of meals and drugs, absorption and distribution of fat (Backhed et al. 2004, Serino et al. 2012). It is involved in vitamin K synthesis (Backhed et al. 2005), the production of mucus by secreting the short chain fatty acids (SCFAs). It causes epithelial regeneration consequently increasing the tightness of the intestine barrier (Burger-van Paassen et al. 2009), and stimulation the angiogenesis (Stappenbeck et al. 2002).
The gut microbiota is relatively stable after the age of 3 years and tends to lose diversity in the elderly (Salazar et al. 2014). Microbial colonization begins shortly after birth, but some studies show the existence of microorganisms in placenta, amniotic fluid, umbilical cord blood, and meconium (Aagaard et al. 2014, DiGiulio 2012, Moles et al. 2013). In the newborns the gut is colonized by facultative anaerobes which create a more suitable environment for the strict anaerobes (Fanaro et al. 2003). It is accepted that the gold standard microbiota in infants is that of full-term vaginally delivered breast-fed babies (Salazar et al. 2014). Consequently the composition of microflora in this stage of life is influenced by many factors, e.g. type of feeding, delivery mode, and use of antibiotics (Penders et al. 2006). The intestine of children fed by breast milk is dominated by Proteobacteria (Fan et al. 2014). It was observed that breast fed infants have higher amounts of bifidobacteria, Bacteroides spp., more varied microbiota and a lower level of potential pathogens than formula-fed babies (Bezirtzoglou et al. 2011, Fallani et al. 2010). Weaning stimulates growth of Bacteroidetes and Firmicutes, and decreases growth of Bifidobacteria and Proteobacteria (Fallani et al. 2011). The induction of solid foods shifts towards bacteria typical for ‘adult’ microbiota (Palmer et al. 2007). This type of gut microflora is dominated by Bacteroidetes and Firmicutes (Arumugam et al. 2011). The ‘adult-like’ intestinal microbiota in the absence of significant ecological stressors represents a high stability and homeostasis (Salazar et al. 2014). Intestinal microbiome diversity is higher among infants than adults (Koenig et al. 2011, Kurokawa et al. 2007). In the elderly, the microbiota represents reduced species diversity causing it less resistant to major fluctuations in response to environmental factors. These changes induce decrease of beneficial bacteria and availability of total SCFA, increase of facultative anaerobes (Salazar et al. 2013, 2014). It was shown, using a mouse model, that adolescence and early adulthood are the critical periods when perturbations in the intestinal microflora and dysregulation of microbiota-gut-brain axis can influence brain development and animal behavior (Desbonnet et al. 2015). These changes can lead to altered cognitive functions and anxious phenotypes in adulthood.
Until recently the relationship between gut microflora and health was largely unknown, mainly due to the lack of methods to study unculturable microorganisms (Salazar et al. 2014). Currently, two methods are commonly used to investigate the relationships between diet, gut microbiome and gut-brain axis: metagenomic (involving culture-independent methods for describing microorganisms) and gnotobiotic (the raising of animals in germ-free conditions at various stages of life and different microflora compositions) (Kau et al. 2011, Turnbaugh et al. 2009, Wikoff et al. 2009).
Our knowledge about the composition and function of intestinal microflora is still unsatisfying (Arumugam et al. 2011) because of dramatic changes in cultural traditions, the growth of population, social and economic status, and agriculture affecting the diet modification. Understanding how these dietary changes affect human gut microflora represents an area of scientific need and challenge (Kau et al. 2011). Advances in modern life such as use of antibiotics, vaccination, high-calorie diet and cleaning products bring significant changes (Flint 2012). Furthermore, the personal profile of the microbiome is continually influenced and changed by diet, genetics, sex and age (Jumpertz et al. 2011, Kau et al. 2011). The microbiota profile might be a valuable representation of the personal environmental history: its dynamic nature and diversity determined to date extends far beyond what researchers expected (Zhou and Foster 2015).
The main diseases investigated in the context of a correlation between gut dysbiosis and development of diseases are: inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), Crohn’s disease, autoimmune and allergic diseases, obesity, neurological and psychiatric disorders (Andoh and Fujiyama 2006, Dash et al. 2015, Elson and Alexander 2015, Fond et al. 2015, Garrett et al. 2007, Ley et al. 2005, Macdonald and Monteleone 2005, Macpherson and Harris 2004, Mangiola et al. 2016, Mayer et al. 2014, Principi and Esposito 2016, Serino et al. 2012, Turnbaugh et al. 2006, Zhou and Foster 2015).
Bidirectional communication between brain and gut microflora has been reported by many authors (Critchfield et al. 2011, DellaGioia and Hannestad 2010, Forsythe et al. 2010, Grenham et al. 2011, Mayer et al. 2014, Messaoudi et al. 2011). Not only physical and psychological stressors may affect the composition and metabolic activity of the gut microbiota, but it is also suggested that the intestinal microbiome affects the brain by the humoral and neuronal mechanisms with particular attention to the vagus nerve (Dash et al. 2015). Signals from the brain may influence sensory, motor, and secretory modalities of the GI tract, and signals from the GI tract influence brain functions, however, the exact mechanisms are not well understood (O’Mahony et al. 2011, Principi and Esposito 2016).
The existing brain-gut axis is further supported by using antibiotics and usually probiotics (defined as living organisms, which taken in appropriate amounts cause health benefits to the host (Bravo et al. 2012) as a treatment for many diseases. Administration of probiotics as food ingredients or supplements can be beneficial for the host. They consist primarily of lactic acid-producing bacteria, such as lactobacilli, lactococci, bifidobacteria and yeasts (e.g. Saccharomyces boulardii) (Critchfield et al. 2011). Probiotics restored gut physiology in stress caused by neonatal maternal separation model by regulating the interaction between mucosa and bacteria and reducing hypothalamic–pituitary–adrenal axis (HPA) hyperreactivity in rats (Gareau et al. 2007).
Diet modification of gut microbiota composition may affect the inflammatory mechanisms (Cani et al. 2007) and damage the intestinal barrier and consequently facilitate the inflow of harmful substances like bacterial metabolites from gut to lumen (de La Serre et al. 2015, Sen et al. 2017). It was observed that high-sugar diet induces gut inflammation and alters vagal gut-brain communication (Sen et al. 2017), as well as high-fat diet causing vagal remodeling can be the reason for alterations in neuronal signaling (Vaughn et al. 2017). Interestingly, it was shown in rats that interferences of vagal afferent signaling are able to cause obesity in a diet-induced models (de Lartigue et al. 2012, Sen et al. 2017), thus, dysregulation of vagal communication between gut and brain is hypothesized to play a role in pathogenesis of obesity and related diseases (Sen et al. 2017). Moreover, microbiota signals affecting the brain can be changed by vagal afferents (Vaughn et al. 2017, Wang et al. 2002). These authors found that eating too much sugar can cause gut inflammation or diminish gut permeability, which combined with dysbiosis may effect endotoxemia (defined as too much circulating lipopolysaccharides, LPS) (Sen et al. 2017).
LPS, also known as lipoglycans or endotoxins, are found in the outer membrane of Gram-negative bacteria, which elicit strong immune responses in animals. They are the markers showing brain-gut microflora bidirectional communication (Bengmark 2013). Antibiotic reduction of luminal LPS concentration attenuates the HPA axis stress response and increases hypothalamic expression of pro-inflammatory cytokines, such as tumour necrosis factor-α (TNF-α), interleukin 6 (IL-6), IL-1β (Ait-Belgnaoui et al. 2012, Theoharides et al. 2013). Even low doses of LPS may cause fatigue, anorexia, depressed mood and apathy (DellaGioia and Hannestad 2010) characteristic of depressive disorder (Dunn and Swiergiel 2005), and inflammation-related states such as autoimmune disease (Johnson et al. 2005). LPS are a potent proinflammatory factors able to alter neuronal activity in the limbic system (e.g. it can increase activity of amygdala) (Haba et al. 2012), and to activate vagal afferent neurons (de Lartigue et al. 2012).
Microbial metabolites are important immunomodulators (Qiu et al. 2012). SCFAs are the end-products of microbial fermentation of macronutrients and not constitutively digested by humans. The missing enzymes are delivered by bacteria, therefore SCFAs are good markers of intestinal microflora composition (Kau et al. 2011), e.g. Clostridia spp. and Bacteroides spp. are important SCFA producers. Major effects of these compounds are the modification of mitochondrial functions (by the citric acid cycle, carnitine metabolism or epigenetic modulation of genes controlling brain function) (Principi and Esposito 2016). Gut microflora can also influence the central nervous system (CNS) by endocrine pathway (corticotropin-releasing factor, CRF) (Rodino-Janeiro et al. 2015) or by modification blood-brain barrier (BBB) (Braniste et al. 2014). There were observed higher levels of these components in the “leaky gut syndrome (LGS, the increased gut permeability) (Critchfield et al. 2011).
The nucleus of the solitary tract (NTS) and dorsal motor nucleus of the vagus (DMV) are the first stations receiving information about nutrition status from the GI tract (Rogers and McCann 1993). It was shown that a high-fat diet, by changing the gut microbiota composition, is able to cause endotoxemia and neuronal damage to the NTS and DMV. This effect includes activation of microglia and vagal remodeling in these regions (Vaughn et al. 2017). Effective treatment by minocycline in rats resulted in normalization of gut microbiota composition and protection against neuronal damage (Vaughn et al. 2017).
Autism spectrum disorders (ASD) are defined by impairments in verbal and non-verbal communication, social interactions, decreased verbal skills, repetitive behavior, insistence to routines, and unusual response to sensory stimuli (Critchfield et al. 2011, Williams et al. 2011). Data from the Center of Disease Control in the USA indicate that as many as 1/80 children have ASD (Williams 2012) and the diagnosis of ASD has increased dramatically over the last years (King and Bearman 2011). Among the potential causes of the rising incidence are broadening of diagnostic criteria and greater awareness among health care professionals (MacFabe et al. 2007), however, one cannot rule out other causes. The prevalence of ASD is between four and eight times higher in males than in females (Bertrand et al. 2001). The lack of knowledge on distinct pathogenesis of ASD and specific biomarkers are important obstacles in developing effective treatments (Theoharides et al. 2013).
Possible risk factors for developing ASD are prenatal exposures to thalidomide, valproic acid, and ethanol (Arndt et al. 2005). Although some parents report an association between abdominal discomfort in their children (e.g. constipation, colic, gastroesophageal reflux and diarrhea) and the onset of autistic symptoms (MacFabe et al. 2007), the prevalence of GI symptoms in autistic children is not precisely defined and ranges between 9 to 70% (Buie et al. 2010). Probably the lower scores are obtained in population studies, whereas the higher scores are defined in specialized GI clinics. Moreover, in these children a high frequency of GI dysfunction is usually associated with increased irritability, aggressive behavior, tantrums, and sleep disturbances (Critchfield et al. 2011).
Some authors correlate ASD symptoms with immune dysfunction and increased inflammatory markers. Proinflammatory cytokines: IL-6, TNF and monocyte chemotactic protein 1 (MCP-1) were found in cerebrospinal fluid of ASD patients (Li et al. 2009b, Onore et al. 2012, Theoharides et al. 2012, Vargas et al. 2005). Methods such as histology, immunochemistry and flow cytometry revealed infiltration of immune cells (e.g. lymphocytes with proinflammatory phenotype CD3+ TNFα+ cells or CD3+ IFNγ+ cells, monocytes, NK cells) in the GI tract of autistic children (Ashwood and Wakefield 2006, Furlano et al. 2001, Torrente et al. 2002).
It is documented that higher serum LPS levels occur in autistic patients with worse social interactions in the comparison to healthy controls (Emanuele et al. 2010). LPS levels correspond to increased IL-1β and IL-6 levels, responsible for inflammatory and immune dysregulation in autism (Emanuele et al. 2010). LGS is responsible for bacteria migration through the intestinal barrier to blood and increase of LPS serum levels in humans (Erridge et al. 2007). Bacterial components in the blood may release inflammatory responses and consequently affect neuronal signaling (Critchfield et al. 2011, Emanuele et al. 2010).
Diet is also thought to influence children with ASD, e.g. a Western diet, depending on inflammatory state, can cause anxiety-like behavior and memory problems (Ohland et al. 2013). The high prevalence of ASD in India (approximately 2 million) may be correlated with typical Indian carbohydrate-rich diet and consequently predominance with of genus Prevotella and Megasphaera (Bhute et al. 2016, Pulikkan et al. 2018). The Veillonellaceae family, which were increased in children with ASD in comparison to healthy controls, was also associated with a carbohydrate-rich diet (including gluten) (Ercolini et al. 2015, Pulikkan et al. 2018). These findings confirm the thesis suggesting that diet induced dysbiosis may be important in pathomechanism of ASD.
Autistic children are characterized by higher levels of fermentation products than corresponding healthy controls (Wang et al. 2012). Phenols, amines, ammonia can be toxic to the large bowel suggesting that gut microflora and intestinal barrier are important in the pathogenesis of ASD (Nowak and Libudzisz 2006). Propionic acid (PPA) is the end-product of enteric bacteria in the intestine (Shultz et al. 2008) and a common preservative added to refined wheat and dairy products (Brock and Buckel 2004). PPA is able to affect autistic behaviors (Critchfield et al. 2011), e.g. higher occurrence of autistic symptoms shortly after the eating of refined wheat and dairy were observed (MacFabe et al. 2007). The authors report a significant improvement in child’s behavior following the elimination of these products from the diet, especially in speech and communication skills, lower hyperactivity, better focusing and night sleep with concurrent resolution of GI symptoms (Jyonouchi et al. 2002). Experimental intraventricular administration of PPA in a rat model demonstrated changes in animal behavior (MacFabe et al. 2007, Shultz et al. 2008). PPA might be responsible for behavioral, neuropathological and biochemical abnormalities observed in autism and might represent a connection factor between dietary or derived metabolites along with genetic predisposition, and subsequent symptoms of ASD (MacFabe et al. 2007, Wajner et al. 2004).
Differences in gut microbiota between children with autism and healthy controls were described in affected children: 10 times higher amount and diversity of Clostridium spp. (Finegold et al. 2002, Parracho et al. 2005, Song et al. 2004), changed Firmicutes: Bacteroides ratio (the lower levels of Firmicutes and higher of Bacteroides) (Finegold et al. 2010), the increase of: Bacteroidetes, Alcaligenaceae family, Lactobacillus and Sutterella genera, and the decreased levels of Prevotella spp. and Bifidobacterium spp. (Adams et al. 2011, Finegold et al. 2010, Kang et al. 2013). It should be noted that Bacteroidetes produce PPA and other SCFAs, and experimental injection of any SCFA into cerebral ventricles of rats caused typical autistic behavior (MacFabe et al. 2007). Williams et al. (2011) observed contradictory decreased levels of Bacteroidetes and increased Firmicutes/Bacteroides ratio. The explanation for this may be using different materials: most authors analyzed the fecal samples, whereas in this particular study authors investigated ileal and cecal biopsies materials.
Short-term improvement was observed after vancomycin treatment in eight out of eleven children with regressive, onset autism, but it largely waned at follow-up (Critchfield et al. 2011, Sandler et al. 2000). Although not suggesting the usefulness of therapy, these results support a possible gut microflora-brain connection.
Treatment of mice exhibiting autistic behaviors by Bacteroides fragilis repaired the intestinal permeability by tight junction protein expression and production of IL-6 (Hsiao et al. 2013). Using probiotics in treatment of autistic children can improve their behavior, but it needs to be established in well-controlled trials with sufficient group sizes (Critchfield et al. 2011).
Although there is evidence that gut dysbiosis is involved in pathogenesis of ASD, some studies did not show differences in the composition of gut microflora between autistic children and healthy controls (Gondalia et al. 2012). The principal limitations of the studies include the number of patients, the differences among groups (diverse lifestyles, environmental risk factors, habits and diet intake) (Emanuele et al. 2010), sometimes not properly examined treatment strategies, e.g. fecal microbiota transplantation (Evrensel and Ceylan 2016). Despite these limitations proved changes in gut microflora composition, modifications of immunological markers and intestinal barrier provide a clue for future treatments.
Depression is characterized by low mood, low self-esteem and loss of interest in normally enjoyable activities (Kessler et al. 1996, Naseribafrouei et al. 2014), and its diagnosis requires the occurrence minimum of five symptoms from the APA 2000 list (DellaGioia and Hannestad 2010), whereas anxiety is described as a common form of mood disorder with nervous, endocrinal, and immunological pathogenesis (Wang and Kasper 2014). A severe bout of depression may lead to death, not only by committing suicide (Dome et al. 2009). Scientist predict that one of six persons will experience at least one episode of depression during their lifetime (Kessler et al. 2005).
It is hypothesized that depression may result from neuroimmunological dysregulation (Dantzer et al. 2008, Wang and Kasper 2014). The direct correlation between gut microbiota and depression remains unclear, but indirect evidences including inflammatory, stress or signaling pathways were described (Dinan and Cryan 2013, Foster and McVey Neufeld 2013). Clinically minocycline (second generation tetracycline) was successfully tested as a treatment for depression (Soczynska et al. 2012).
In rodents acute stress causes increased gut permeability (Julio-Pieper et al. 2014), and germ-free (GF) mice exhibit reduced anxiety and increased motor activity in a comparison to specific pathogen free (SPF) mice (Neufeld et al. 2011). There is some evidence for the reverse situation, when the increased intestinal permeability affects psychological stress: the challenge with Citrobacter rodentium in mice caused anxiety-like and increased risk assessment behavior (Julio-Pieper et al. 2014), supporting the correlation between anxiety-like behavior and gut microbiota composition.
Modifications of traditional lifestyles, among which diet is especially mentioned, were correlated with many mental disorders, mainly depression (Hidaka 2012, Selhub et al. 2014). Population studies showed that “traditional dietary practice” was related to lower risk of depression and anxiety, e.g. typical for Japanese fermented soy products (Nanri et al. 2010). These findings were confirmed in animals studies: mice fed by beef presented higher gut microbial diversity, better reference memory and decreased anxiety in comparison to chow-fed ones (Li et al. 2009a). Moreover, drinking water enriched with Lactobacillus helveticus and Bifidobacterium longum can increase nerve cell resiliency during experimental physiological stress in rats (Girard et al. 2009).
Suggestions that depression is characterized by cell-mediated immune activation and inflammation were published by Maes et al. already in early 1990-ties (Maes et al. 1990, 1991, Maes 1993). Investigators have observed that depression coexist with other inflammatory diseases (rheumatic diseases, inflammatory bowel disease, multiple sclerosis) (Howren et al. 2009, Karakula-Juchnowicz et al. 2014) and abnormalities in serum cytokines correlate with depression (Dantzer et al. 2008). Higher levels of proinflammatory IL-6 and TNF-α were found in affected patients as compared to healthy controls (Bremmer et al. 2008, Dome et al. 2009, Dowlati et al. 2010, Hestad et al. 2003, Sluzewska et al. 1995, Zorrilla et al. 2001). Moreover, successful antidepressant treatment for major depressive disorder reduced serum cytokine levels of IL-1β and IL-6 (Hannestad et al. 2011).
Composition of the gut microflora and its impact on symptoms of depression was analyzed (Dash et al. 2015, Dinan and Cryan 2013, Mayer et al. 2014, Naseribafrouei et al. 2014) and three general mechanisms have been proposed: 1) through inflammation directly, 2) through the HPA, or 3) through interference with neurotransmitter signaling (DellaGioia and Hannestad 2010, Foster and McVey Neufeld 2013). Importantly, abnormal activities of the HPA axis have been diagnosed in patients with various mental disorders, such as schizophrenia (Walker and Diforio 1997), depression (Holtzheimer and Nemeroff 2006), posttraumatic stress disorder (de Kloet et al. 2005).
As mentioned above, LPS may be an important factor contributing to psychiatric disorders (Berk et al. 2013, Qin et al. 2007). Endotoxin administration to healthy male volunteers caused response with dose-related elevations in body temperature and heart rate, increases in plasma (IL-6, IL-10, TNF-α and IL-1 receptor antagonist IL-1Ra), salivary and plasma cortisol, plasma norepinephrine, and these changes were accompanied by dose-related decreased mood, increased anxiety levels and modulations of emotional memory (Grigoleit et al. 2011). IgA- and IgM-mediated inflammatory responses to LPS have been also shown to be elevated in patients with depression (Maes 2011).
Some authors observed differences in gut microbiota in patients with depression compared to healthy controls: increased levels of Enterobacteriaceae family and Alistipes spp. (Jiang et al. 2015, Naseribafrouei et al. 2014), which can be modified by changes in diet (Naseribafrouei et al. 2014). Interestingly, Alistipes spp. are overrepresented in irritable bowel syndrome (IBS) (Saulnier et al. 2011), suggesting a possible common mechanisms (Zhou and Foster 2015). A higher Firmicutes: Bacteroides ratio in patients with IBS correlated with clinically overt anxiety and depression (Jeffery et al. 2012), thus supporting a relationship between depression and gut microbiota composition. Conversely, a negative correlation was shown between the expression of Faecalibacterium spp. and Bacteroidetes, and the occurrence of depression (Jiang et al. 2015, Naseribafrouei et al. 2014). Similarly to obese patients (Ley et al. 2006) these relationships may provide link between obesity and depression.
Experimental studies performed on animals investigating the role of gut microbiota composition in anxiety, demonstrated increased stress-reactivity in GF mice (Sudo et al. 2004). Interestingly, GF mice are smaller and show higher anxiety levels than matched SPF ones (Backhed et al. 2004, Luna and Foster 2015). GF mice showed increased anxiety-like behaviors in the open-field and marble-burying tests than specific pathogen free animals and mono-association of GF mice with Blautia coccoides reduced anxiety-like behaviors (Nishino et al. 2013). The effect is bidirectional since the murine gut microbiota can influence emotions, and stress and anxiety promote the growth of Odoribacter spp., Alistipes spp. and family Coriobacteriaceae (Bangsgaard Bendtsen et al. 2012). Separation of rats from their mother showed that neonatal stress induces long-term modifications in the intestinal microbiota diversity and composition (Garcia-Rodenas et al. 2006, O’Mahony et al. 2009), e.g. causes decrease of Verrucobacteria and increase of Clostridium spp. (Aguilera et al. 2013), but feeding rats with B. infantis 35624 normalized immune response, behavior and noradrenaline concentrations in the brain stem (Desbonnet et al. 2010).
GABA can be synthesized by intestinal bacteria: Lactobacillus brevis and Bifidobacterium dentium (Barrett et al. 2012). Long-term administration of L. rhamnosus to rats modulates the expression of GABA in CNS, leading to reduced levels in the hippocampus, amygdala and locus coeruleus, but increased levels in cortical regions (Bravo et al. 2011). Furthermore, GABA decreases the levels of corticosterone induced by depression and anxiety-related symptoms (Mangiola et al. 2016). Mice treated with Bifidobacterium longum NC3001 revealed reduced anxiety-like behaviors (Bercik et al. 2010). The presented studies indicate that selected probiotics can be used successfully in treatment of depression and anxiety symptoms (Bravo et al. 2012).
Dietary factors can be associated with anxiety-like behaviors in mice, e.g. long-term high fat diet increased anxiety levels (Del Rosario et al. 2012). The mice fed with beef showed greater bacteria diversity and less anxiety-like behaviors in comparison to animals with standard chow diet (Li et al. 2009a).
A double-blind, placebo-controlled, randomized clinical trial with probiotic formulation (L. helveticus and B. longum) administered for 30 days alleviated psychological distress in healthy human volunteers (measured by the Hopkins Symptom Checklist) (Messaoudi et al. 2011). In a similar study, healthy female volunteers consumed fermented milk product with some probiotics for four weeks (Bifidobacterium animalis subsp. Lactis, Streptococcus thermophilus, Lactobacillus bulgaricus and L. lactis subsp. Lactis) indicated an influence on brain activity in emotion-related areas, e.g. reduced activity of sensory brain network, frontal, prefrontal and temporal cortices (Tillisch et al. 2013).
Despite over 100-year history of research, the etiology of schizophrenia is still not fully understood, nonetheless, an interaction of environmental and genetic factors is still strongly considered (Joseph et al. 2017, Nemani et al. 2015). Schizophrenia typically develops at age between 15–45 years (Crow 1980) and has similar prevalence rates worldwide despite the different diagnostic criteria in various parts of the world (Arneth 2017, Sartorius et al. 1986). Due to the devastating course of untreated schizophrenia presenting with characteristic ‘positive’ (delusions and hallucinations) (Morris et al. 2013) and ‘negative symptoms’ (apathy, anhedonia, amotivation) (Rabinowitz et al. 2012) as well as dysfunctions in learning and memory (Gold et al. 1997), the patients unquestionably require extensive care (Szkultecka-Debek et al. 2016).
Epidemiological studies showed that patients with schizophrenia, and members of their family, have a higher frequency of autoimmune disorders (Benros et al. 2012), atopic disease (Hornig 2013), and celiac disease (Dickerson et al. 2014). The latter is a risk factor for the development of schizophrenia (Severance et al. 2012) suggesting that schizophrenia is related to immuno-inflammatory activity (Karakula-Juchnowicz et al. 2016). The higher CRP serum levels in schizophrenic patients were found as a marker of inflammation (Dickerson et al. 2013), but the origin of inflammatory process is still unclear (Joseph et al. 2017). Polymorphisms in IL-1β, IL-6, and soluble IL-6 receptors (sIL6R) are postulated to be a risk factor for schizophrenia (Hudson and Miller 2016), and the correlation between inflammatory markers level and severity of clinical symptoms were recently reported (Hope et al. 2013).
Some authors indicate that immunological disturbances may result from a dysfunction of the brain-gut axis (Karakula-Juchnowicz et al. 2016) caused by LGS. Indicated evidence of damage to the intestinal barrier is: 1) histological (in 82 autopsies patients with schizophrenia were diagnosed with: colitis in 92%, enteritis in 88% and gastritis in 50% (Hemmings 2004, Karakula-Juchnowicz et al. 2016), 2) immunological – presence of intestinal inflammation markers (higher levels of food antigen antibodies: bovine milk casein and wheat-derived gluten (Severance et al. 2012), increased serum levels of proinflammatory cytokines, especially IL-1β, IL-6, IL-8 (Fillman et al. 2016, Miller et al. 2011), 3) by bacterial translocation markers, e.g., elevated serum levels of antibodies against Saccharomyces cerevisiae (Severance et al. 2012), serum elevation of bacterial markers, e.g. sCD14 and lipopolysaccharide binding protein-LBP (Severance et al. 2013). It was suggested that schizophrenia might also be associated with infection of Clostridium difficile producing phenylalanine derivative affecting CNS in a similar way as in autism (Shaw 2010).
Investigators have found that diet can change human behavior. It was shown that fermented foods improved cognitive function (Kim et al. 2016, Selhub et al. 2014). Moreover, schizophrenic patients present abnormal sensitivity to gluten and bovine casein (Cascella et al. 2011, Karlsson et al. 2012, Severance et al. 2010), and gluten free diet improved behavior and increased free L-tryptophan levels (Jackson et al. 2012) indicating that LGS can be responsible for gluten/casein sensitivity (Severance et al. 2012). Epidemiological studies show that metabolic syndrome is another clinical condition correlated with schizophrenia, its incidence is 20% higher than in general population (Mitchell et al. 2013). Ketogenic diet may improve the clinical course of schizophrenia, like normalization of behavior (probably by regulation of glutamate neurotransmission, GABA function and glucose metabolism), which supports the existing links between schizophrenia and GI tract (Kraeuter et al. 2015, Pacheco et al. 1965).
It is documented that gut microbiota affects the CNS by modulating: brain-derived neurotropic factor (BDNF), which expression is responsible for cognitive dysfunction (Nieto et al. 2013) and its decrease was found in patients with schizophrenia, anxiety disorders and Alzheimer’s disease (Carlino et al. 2013, Sudo et al. 2004). BDNF expression is lower in GF animals correlating with increased anxiety behavior and progressive cognitive dysfunction (Carlino et al. 2013, Foster and McVey Neufeld 2013). The decreased level of NMDA in GF animals is responsible for controlling the synaptic plasticity in memory function in the cortex and hippocampus (Nemani et al. 2015, Sudo et al. 2004). NMDA receptor hypofunction is considered to be one of the most important pathophysiology of schizophrenia (Nemani et al. 2015). The gut microbiota modulates synaptophysin involved in the brain development (Douglas-Escobar et al. 2013, Nemani et al. 2015).
The current opinion suggests that gut dysbiosis may exert a harmful influence on brain development and functioning, regulation of immunology system and metabolic function in schizophrenia (Caso et al. 2016, Nemani et al. 2015), however, to date, there has been no direct evidence of dysbiosis in schizophrenia patients (Nemani et al. 2015).
Animal models are helpful to elucidate the role of gut microbiota in the pathogenesis of schizophrenia: it was shown that GF mice represent schizoid behavior (Caso et al. 2016). Furthermore, the behavioral deficits are more severe in males, similarly to human epidemiology of SCZ (Dinan et al. 2014). The social behavior in GF mice was examined by using classical ‘three-chamber sociability test’ showing that GF animals have problems in communication and with emotions recognition (Desbonnet et al. 2014).
Oral supplementation of mice by Bacteroides fragilis and resulting correction of gut permeability ameliorates defects in communication, anxiety-like and sensorimotor behaviours (Hsiao et al. 2013). Oppositely, treatment with Lactobacillus rhammosus and Bifidobacterium animals subsp. Lactis showed no significant effects on psychiatric symptoms (Dickerson et al. 2014).
In a 16-week clinical trial employing treatment with a second generation tetracycline-minocycline showed a reduction of negative symptoms in patients with early stage schizophrenia in SANS (Scale for the Assessment of Negative Symptoms), PANSS (Positive and Negative Syndrome Scale) and CGI (Clinical Global Impression Scale) (Liu et al. 2014).
Antibiotics and probiotics combined with a gluten and casein-free diet might have a therapeutic potential in some schizophrenia patients (Latalova et al. 2017). To make dietary interventions successful support from scientists, dieticians, family members, and neuropsychiatric clinicians is necessary (Joseph et al. 2017). Further clinical trials are needed to confirm these theses.
The prevalence of mental disorders is predicted to increase (Fond et al. 2015) and microbiologists, from Louis Pasteur and Ilya Mechnikov to the present, have tried to understand the role of microbiota for our health and in the pathogenesis of diseases (Backhed et al. 2005). Multiple studies, with antibiotic and probiotic treatments, fecal microbiota transplantation, and GF animal studies have been used to assess the impact of microbiota on brain function demonstrating differences between healthy human gut microflora composition and that of patients with neuropsychiatric diseases (Cryan and Dinan 2012, Dinan and Cryan 2013, Zhou and Foster 2015). It is well known that gut microbiota composition and functioning depends largely on diet, which consequently can affect also nervous system and metabolism, but these investigations need further studies (Moos et al. 2016). Identification of the signaling pathways between the microbiota and the brain in humans is needed to expand our understanding of microbiota gut–brain interactions. If confirmed, modulation of the gut microflora can be a novel target for the treatment (Tillisch et al. 2013).
Currently, most data examining brain-gut relationships have been collected in experimental animals, but they can be considered as valuable for future human studies (Principi and Esposito 2016). Although, it is not clear whether psychiatric diseases depend on gut microbiota modification or a single bacteria species (Principi and Esposito 2016), modification of gut microbiota and the gut-brain communication may be promising treatment for neuropsychiatric diseases.

domain: medical


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Lu X.C.,Zhejiang Hospital
Zhonghua yi xue za zhi | Year: 2016
OBJECTIVE: To evaluate the efficacy of tigecycline for treatment of ventilator-associated pneumonia in critically ill elderly patients.METHODS: Data of critically ill elderly patients with ventilator-associated pneumonia treated with tigecycline in the intensive care unit was collected from June 2011 to March 2014 in this retrospective study, to evaluated the clinical efficacy of tigecycline.RESULTS: A total of 79 patients (83.5% male) were included, the mean age was 84 years old (rang, 65 years to 100 years old). Acinetobacter baumannii (39.1%), Pseudomonas aeruginosa (35.0%) and Klebsiella pneumonia (23.8%) were the most common pathogens.All patients were treated with tigecycline, 54.4% combined with other antimicrobial agents, 35.4% treated with double dose of tigecycline, and the mean course of antibiotic treatment was 9 days (range, 2 days to 22 days). After treatment, clinical success were recorded in 44 patients (55.7%), clinical failure were recorded in 29 patients, clinical uncertainty were recorded in 6 patients.28 days after treatment, patients' overall mortality was 39.0%.The clinical success rates were associated with acute physiology and chronic health evaluation (APACHE) Ⅱ score less than 15 (the clinical success rates were 72.2% and 41.9% in patients with APACHE Ⅱ score<15 and APACHE Ⅱ score≥15, respectively; P=0.007); treated with double dose of tigecycline (71.4% vs 47.1%, P=0.037) or combination regimens were also had significant difference (67.4% vs 41.7%, P=0.022).CONCLUSIONS: Treatment of tigecycline combined with other antimicrobial agents and double dose of tigecycline may both can improve clinical efficacy in critically ill elderly patients with ventilator-associated pneumonia.
Sun X.-D.,Zhejiang Provincial Peoples Hospital |
Liu X.-E.,Zhejiang Hospital |
Huang D.-S.,Zhejiang Provincial Peoples Hospital
Oncology Reports | Year: 2013
Curcumin, a phenolic compound extracted from Zingiberaceae turmeric, has strong anti-inflammatory, antioxidant and antitumor properties. However, the anti carcinogenic mechanism of curcumin has yet to be fully elucidated. Epithelial-mesenchymal transition (EMT) induced by transforming growth factor-β1 (TGF-β1) is involved in the promotion of tumor invasion and metastasis, and is closely related to the drug resistance of tumor cells. The abnormal activation of Hedgehog signaling also plays an important role in tumorigenesis and metastasis. In order to investigate whether curcumin can reverse the TGF-β1-stimulated EMT of pancreatic cancer PANC-1 cells, and its possible mechanism, the pancreatic cancer cell line PANC-1 was stimulated with TGF-β1 (5 ng/ml) for 7 days to induce formation of EMT, and the TGF-β1-stimulated PANC-1 cells were treated with different concentrations of curcumin (10, 20 and 30 μmol/ml) for 48 h. The growth inhibition rate of the cells was measured by MTT assay, apoptosis was detected by flow cytometry, the expression levels of Shh, GLI1, E-cadherin and vimentin were detected by western blot analysis, and cell invasion and migration ability were examined by Transwell cell invasion assay and wound healing assay. Following stimulation with TGF-β1, the expression levels of Shh, GLI1 and vimentin in the TGF-β1-stimulated group were significantly increased, compared with those in the control group (P<0.01, respectively). The expression levels of E-cadherin in the TGF-β1-stimulated group were significantly decreased, compared with those in the control group (P<0.01). The TGF-β1-stimulated PANC-1 cells were treated with curcumin and the results showed that curcumin significantly inhibited TGF-β1-stimulated PANC-1 cell proliferation and induced apoptosis, compared with other groups (P<0.01), and expression levels of Shh, GLI1 and vimentin in the curcumin-treated group were significantly decreased compared with those in the control group (P<0.01, respectively). The expression level of E-cadherin in the curcumin-treated group was significantly increased compared with that in the control group (P<0.01). Cell invasion in the curcumin-treated group (30μmol/ml) was significantly decreased compared with that in the control group (P<0.01). The scratch wounds in the curcumin-treated group healed slower compared with those in the control group (P<0.01). Curcumin significantly inhibited the invasion and migration of TGF-β1-stimulated PANC-1 cells. These results indicate that curcumin can inhibit the proliferation of TGF-β1-stimulated PANC-1 cells, it can induce apoptosis, and reverse the EMT. The possible underlying molecular mechanisms are through inhibition of the Shh-GLI1 signaling pathway.
Chen S.,Zhejiang University |
Zhao Y.,University of Sydney |
Zhang Y.,Zhejiang Hospital |
Zhang D.,University of Canberra
PLoS ONE | Year: 2014
p Conclusion/Significance: Fucoidan exerts its anti-tumor function by modulating ER stress cascades. Contribution of ER stress to the fucoidan-induced cell apoptosis augments our understanding of the molecular mechanisms underlying its antitumour activity and provides evidence for the therapeutic application of fucoidan in cancer.
Chen X.,Zhejiang Hospital |
Mao G.,Zhejiang Hospital |
Leng S.X.,Johns Hopkins University
Clinical Interventions in Aging | Year: 2014
Frailty is a common and important geriatric syndrome characterized by age-associated declines in physiologic reserve and function across multiorgan systems, leading to increased vulnerability for adverse health outcomes. Two major frailty models have been described in the literature. The frailty phenotype defines frailty as a distinct clinical syndrome meeting three or more of five phenotypic criteria: weakness, slowness, low level of physical activity, self-reported exhaustion, and unintentional weight loss. The frailty index defines frailty as cumulative deficits identified in a comprehensive geriatric assessment. Significant progress has recently been made in understanding the pathogenesis of frailty. Chronic inflam-mation is likely a key pathophysiologic process that contributes to the frailty syndrome directly and indirectly through other intermediate physiologic systems, such as the musculoskeletal, endocrine, and hematologic systems. The complex multifactorial etiologies of frailty also include obesity and specific diseases. Major clinical applications include risk assessment and stratification. This can be applied to the elderly population in the community and in a variety of care settings. Frailty may also be useful for risk assessment in surgical patients and those with cardiovascular diseases, cancer, or human immunodeficiency virus infection, as well as for assessment of vaccine effectiveness in older adults. Currently, exercise and comprehensive geriatric interdisciplinary assessment and treatment are key interventions for frailty. As understanding of the biologic basis and complexity of frailty further improves, more effective and targeted interventional strategies and innovative geriatric-care models will likely be developed. © 2014 Chen et al.
Si C.-J.,Zhejiang Hospital
European Journal of Cancer Prevention | Year: 2016
Previous studies have attempted to assess the relation between different dietary patterns and the risk of endometrial cancer (EC); however, a consistent perspective has not been established to date. Therefore, we carried out this meta-analysis to evaluate the associations between dietary patterns and the risk of EC. The most common dietary patterns with high loadings of foods and/or nutrients were selected. A total of 27 studies fulfilled the inclusion criteria and were included in the present meta-analysis. There was evidence of a decreased risk of EC in the highest compared with the lowest categories of healthy dietary pattern [odds ratio (OR)=0.74; confidence interval (CI): 0.62–0.88; P=0.008]. An increased risk of EC was shown for the highest compared with the lowest category of a western-style dietary pattern (OR=1.37; CI: 1.15–1.64; P=0.0005). No significant association with the risk of EC was found in the highest compared with the lowest category of alcohol-drinking pattern (OR=0.98; CI: 0.73–1.30; P=0.87). The results of this meta-analysis indicate that some dietary patterns may be associated with the risk of EC. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
Lixin X.,Zhejiang Hospital
Quintessence international (Berlin, Germany : 1985) | Year: 2010
OBJECTIVE: This retrospective study evaluated the success rate of a fixed retrievable prosthesis based on an electroforming technique combining the advantages of screw- and cement-retained principles. METHOD AND MATERIALS: Forty patients (17 men and 23 women) with a mean age of 62.2 years were treated. A total of 353 implants were placed in the edentulous maxilla, mandible, or both jaws to allow prosthetic rehabilitations with 55 fixed prostheses. Clinical success of the implants was based on the criteria of Buser. Technical complications monitored throughout the wearing period are described. Retrievability of the restoration with a conventional crown remover was checked at 6, 12, and 36 months. The cumulative survival rate of the implants was measured. RESULTS: After a mean observation period of 4.08 years (range 22 to 62 months), a cumulative survival rate of 99.15% was recorded for the 234 maxillary implants (234 Camlog RootLine, Camlog) and for the 119 mandibular implants (72 Camlog RootLine, 47 Camlog ScrewLine). Three implants failed before prosthetic loading. Monitored technical complications were seen in 10.91% of the restorations; they comprised ceramic chip-off and relining. CONCLUSIONS: This fixed implant-retained prosthesis based on electroforming indicates a comparable clinical efficacy to other techniques and allows scheduled retrieval.
Feng Y.-L.,Zhejiang Hospital
European Journal of Cancer Prevention | Year: 2016
The analysis of dietary patterns has recently drawn considerable attention as a method of investigating the association between the overall whole diet and the risk of colorectal cancer. However, the results have yielded conflicting findings. Here, we carried out a meta-analysis to identify the association between dietary patterns and the risk of colorectal cancer. A total of 40 studies fulfilled the inclusion criteria and were included in this meta-analysis. The highest category of ‘healthy’ dietary pattern compared with the lowest category was apparently associated with a decreased risk for colorectal cancer [odds ratio (OR)=0.75; confidence interval (CI): 0.68–0.83; P<0.00001]. An increased risk of colorectal cancer was shown for the highest compared with the lowest category of a ‘western-style’ dietary pattern (OR=1.40; CI: 1.26–1.56; P<0.00001). There was an increased risk of colorectal cancer in the highest compared with the lowest category of ‘alcohol-consumption’ pattern (OR=1.44; CI: 1.13–1.82; P=0.003). The results of this meta-analysis indicate that a ‘healthy’ dietary pattern may decrease the risk of colorectal cancer, whereas ‘western-style’ and ‘alcohol-consumption’ patterns may increase the risk of colorectal cancer. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
Zhan J.,Zhejiang University |
Han Q.,Zhejiang Hospital |
Wang K.,Chinese Academy of Sciences
Expert Opinion on Investigational Drugs | Year: 2013
Introduction: Small cell lung cancer (SCLC) is one of most aggressive cancers and only modest improvements have been achieved in overall survival over last 30 years. In recent years, antibody therapeutics has been actively studied and shown promise in treatment of SCLC. Areas covered: A comprehensive literature search through Medline and the registry database of clinical trials (ClinicalTrials.gov) was performed to collect all relevant preclinical and clinical data. The diverse antibody therapeutics which target against different antigens including VEGE-A, CEA, IGF-1R, CD56, EpCAM, CTLA-4, gangliosides GD2 and GD3, Lewis Y and tenascin-C are now under clinical investigation for therapeutic effects in SCLC. Expert opinion: During the last few decades, progresses have been made in antibody therapy for SCLC, however great challenges still remain. The major reasons are the complexity of SCLC and a lack of understanding of cancer immunology. The profound studies of signaling pathways involved in carcinogenesis, proliferation, metastasis and apoptosis in SCLC are crucial for the identification of new therapeutic targets and biomarkers. Moreover, a better understanding of the interplay between cancer and the immune system is a new direction for the design of more effective antibody therapeutics. © 2012 Informa UK, Ltd.
Xu Q.H.,Zhejiang Hospital
Zhonghua nei ke za zhi [Chinese journal of internal medicine] | Year: 2012
To investigate the effects of ω-3 fish oil lipid emulsion via vein on the inflammatory response, immune and organ function in patients with severe acute pancreatitis. A total of 53 patients with severe acute pancreatitis were randomized into conventional therapy plus fish oil group (FO group) and conventional therapy group (CON group). The patients in FO group were treat with ω-3 fish oil lipid emulsion (0.2 g×kg(-1)×d(-1), 10%) based on conventional therapy for 14 days. The level of C-reactive protein (CRP), TG and TC were detected before treatment and at day 7 and day 14 after treatment. CD(4)(+), CD(4)(+)/CD(8)(+) and C(3), C(4) were also detected at day 1 and day 14 after treatment. At the same time, acute physiology and chronic health evaluation II score (APACHEII score), intra-abdominal pressure, negative fluid balance time, enteral nutrition start-time and ICU stay time were observed and recorded. Forty-five out of 53 patients were finally recruited into results statistics. The level of CD(4)(+), CD(4)(+)/CD(8)(+) and C(3) at day 14 after treatment in FO groups improved significantly than that in the CON group (P < 0.05). The levels of CRP, intra-abdominal pressure and APACHE II score at day 7 and day 14 in FO group descended more obviously than that in the CON group (P < 0.05). The negative liquid balance time in FO group (3.55 ± 0.86)days was obvious shorter than that in CON group (4.61 ± 1.12) days, while enteral nutrition start-time (3.86 ± 1.17) days was significantly earlier compared with CON group (5.30 ± 1.61) days (P < 0.05), however ICU stay time and 28 days mortality rate had no significant difference between the two groups. ω-3 fish oil lipid emulsion can decrease the inflammatory response and the negative liquid balance time, improve the immune function and restore bowel function in severe acute pancreatitis patients. Therefore, it maybe provide a new and effective means for severe acute pancreatitis.
Jin Y.,Zhejiang Cancer Hospital |
Zhao L.,Zhejiang Hospital |
Peng F.,Zhejiang Hospital
Clinics | Year: 2013
OBJECTIVE: Patients with stage I non-small cell lung cancer who have undergone complete surgical resection harbor a 30% risk for tumor recurrence. Thus, the identification of factors that are predictive for tumor recurrence is urgently needed. The aim of this study was to test the prognostic value of serum albumin levels on tumor recurrence in patients with stage I non-small cell lung cancer. METHODS: Stage I non-small cell lung cancer patients who underwent complete surgical resection of the primary tumor at Zhejiang Hospital were analyzed in this study. Serum albumin levels were measured before surgery and once again after surgery in 101 histologically diagnosed non-small cell lung cancer patients. Correlations between the pre- and post-operative serum albumin levels and various clinical demographics and recurrence-free survival rates were analyzed. RESULTS: Patients with pre-operative hypoalbuminemia (<3.5 g/dl) had a significantly worse survival rate than patients with normal pre-operative serum albumin levels (≥3.5 g/dl) (p = 0.008). Patients with post-operative hypoalbuminemia had a worse survival rate when compared with patients with normal post-operative serum albumin levels (p = 0.001). Cox multivariate analysis identified pre-operative hypoalbuminemia, post-operative hypoalbuminemia and tumor size over 3 cm as independent negative prognostic factors for recurrence. CONCLUSION: Serum albumin levels appear to be a significant independent prognostic factor for tumor recurrence in patients with stage I non-small cell lung cancer who have undergone complete resection. Patient pre-treatment and post-treatment serum albumin levels provide an easy and early means of discrimination between patients with a higher risk for recurrence and patients with a low risk of recurrence. © 2013 CLINICS.


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|Antique Letter Type Display Table
We have always had a fascination for antique printing letters because they are beautifully crafted hard wood covered with years of ink and tales of the past. They are a part of our history and should be preserved as so. The conception of letterpress printing was in Europe in the 15th century. The creator of the reusable, movable type was Johannes Gutenberg. This type of printing stood the test of time by being the main method of printing for over 400 years. It wasn't until the linotype machine was introduced in the late 19th century that a movement away from wood type was made. The linotype machine remains the primary printing method today. As a result, wooden type became orphaned to antique shops, warehouses, flea markets and most recently, E-commerce. There is a large movement to preserve these antique letter type as they remain an important part of the history of printing.
We began collecting random letterpress type years ago when we would visit antique fairs, flea markets, and thrift shops. We knew the importance of not breaking up complete sets, therefore, we would only buy stranglers. Ken's fascination grew into obsession when he began buying up many broken up sets. The end result was that we had a multitude of beautiful antique, or vintage, letter type that rarely resulted in a match up of its kind. The antique letters ranged in different sizes, fonts, age and condition. It made for a wonderful collage of history and beauty.
Being furniture designers, we thought of ways to incorporate these pieces into unique furniture. We came up with a design using a reclaimed steel base and incasing to display a collage of antique letter type. For the sake of preservation and utilization, we covered the table top with 3/16 low iron, tempered glass. After all, this is considered to be a display case because its substrate, the antique letter type, continues to appreciate in value. This is for an individual who wishes to collect and preserve an important part of printing history.
The display table is 22" x 36" and contains 746 authentic antique letterpress letters. They are arranged inside of a three inch tall .25" oxidized steel frame. The letters are not glued in so that their value is not compromised in any way. The type is protected by 3/16" low iron, tempered glass. The table's top rests on a custom frame with 2" legs. The legs have a reclaimed Jatoba feet insert to protect floors. The best part is that the table is designed for safe transport. The top can be removed for shipping and moving purposes.
|Photographed without the glass top to show detail
|Detailed picture of the reclaimed Jatoba leg inserts
This table is available for purchase. If you are interested or want a custom table, please contact us at firstname.lastname@example.org
This table is now on display at Lost Antiques in the Design District, Dallas.

domain: hobby


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“One summer can change everything.”
With this foreboding Season 3 tagline for Stranger Things, the Duffer brothers have all but guaranteed an exhilarating and emotional third installment in the wildly popular Netflix series. The sci-fi story captured hearts in 2016 with its ’80s nostalgia, binge-able storyline, talented young cast and remarkable visual effects. With this season potentially being the final season, Stranger Things might come to a close—but not before at least one last adventure. Or cataclysmic disaster. Or all of the above.
Hype for the hit show has never been higher. All trailers for this season have been released, and a second batch of Nike’s Stranger Things collection will drop July 1, just days before the entire season debuts on Netflix. With a Fourth of July release date, it seems the Duffer brothers want everyone to spend Independence Day glued to their screens. Well, if we must (Eggo Waffles go well with a summer BBQ, right?).

domain: entertainment


Manchester pension fund signs up to resi
Greater Manchester Pension Fund, the pension scheme for 10 local authorities in Manchester, has signed up to a partnership that will build 240 new homes around the city.
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The question has been asked, is kosher salt kosher? And the answer is yes. In this sense, kosher literally refers to the quantity of the kosher salt used in cooking. When you purchase kosher salt, you are ensured that you're getting a smaller, flat or round kosher salt crystal. This is the best size of kosher salt for kosher cooking, because its higher surface area will allow it to draw more blood from the animal it is used on.
Another important factor when determining kosher salt quality and kosher salt value is the ratio of different elements in the kosher salt. In general, the more kosher flakes, the higher the salt's concentration. Thus, the higher the concentration of kosher salt in sea salt or table salt, the more precious kosher salt you'll get. Table salt contains mostly sodium and chloride, sea salt is mostly magnesium and potassium.
In addition, there are two major factors to consider when choosing kosher sea salts or table salt. First is its location. Sea salt is naturally closer to the shore and therefore has a stronger grip on the earth's surface. The next factor is what type of climate the salt is used in. Sea salt is often used in colder climates because it locks onto the lower elevation of the soil, thus preserving the moisture of the surrounding soil.
In comparison, kosher sea salt has less ability to retain moisture and therefore must be mixed with water to make it moist enough to work properly. Table salt on the other hand is generally made from ground salt and refined to remove all but about 2% of its natural salt content. Because it has less moisture, the more commonly used kosher salt tends to dissolve in the water quicker than table salt. Its ability to dissolve also means it leaves behind dry residue which will clog up your pores and cause blemishes to worse their condition.
Another thing to consider when buying kosher salt is its use in food preparation. Unlike regular table salt, kosher salt is only to be used for kosher food preparation. Kosher fish, for instance, cannot use regular table salt for re-frying. And contrary to popular belief, kosher salt does not have the same effect on animals as regular table salt. Pets are better off with kosher salt.
There is another key benefit of kosher salt that not many people know about. During the kosher salt curing process, tiny air bubbles are formed which are a good source of minerals. The best way to learn more about these beneficial bubbles is to buy a salt recipe book and do your own experimenting. Not only will you increase your enjoyment of this great seasoning, but you'll also add a hint of professional flavour and value to whatever dishes you prepare
In addition to adding trace minerals, kosher salt also brings out the natural flavour in foods. Many chefs rely on kosher salt for added flavour to their favourite dishes. No longer will you have to settle for the "generic" flavours found in regular sea salt. You can now choose the kind you want.
Kosher salt has come along way. No longer is it just an old-fashioned rock salt that taste bland. Now, kosher salt offers health benefits and trace minerals that no other kind of salt can provide. The biggest drawback may be the price. While a traditional rock salt may be slightly more expensive, it is worth the money if you are buying a long-lasting, highly-beneficial salt. If you have not tried kosher, you really owe it to yourself to give it a try, you won't be disappointed!

domain: food


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Just one week after CNN's Don Lemon shut down a guest who dared to raise the issue, there is now an agreement across the ideological spectrum that if Hillary Clinton is going to use her husband Bill as a campaign surrogate and go after her opponents' real or imagined sexism, then, as the headline at liberal Ruth Marcus's Monday evening Washington Post column says, "Bill Clinton's sordid sexual history is fair game."
Meanwhile, a Wall Street Journal editorial, while citing Marcus's column, agrees: "if Mrs. Clinton wants everyone to forget about Bill’s harassment of women, she ought to stop playing the sexism card, or drop Bill as surrogate, or both."
Marcus clearly struggles to remain intellectually honest before ultimately admitting what should be obvious (bolds are mine throughout this post):
Donald Trump ... has a point about (Hillary) Clinton playing the “woman’s card,” and about the male behavior that’s more concerning: her husband’s.
... Clinton’s attempt at outsourced outrage (over Donald Trump's "schlonged" and other comments — Ed.) has the air of a basketball player flopping on the floor for the benefit of the ref. Nothing would make the Clinton campaign happier than some good old-fashioned male chauvinist piggery directed her way — all the better to rile up female voters who seem surprisingly nonchalant about the prospect of electing the first female president.
We’ve seen this playbook before. ...
Marcus went on to recount Mrs. Clinton's history of playing the gender card during her first Senate campaign against Republican Rick Lazio in 2000, her unsuccessful presidential campaign in 2008, and currently against Bernie Sanders, when her surrogates bizarrely accused the Vermont senator of a sexist attack when he contended that "all the shouting in the world" won't solve gun violence.
Continuing with portions of Marcus's column:
Into this gender minefield lumbers Trump, characteristically unbound and deploying a weapon that none of Clinton’s Democratic opponents, past or present, has dared to mention. He played the Bill Card.
... “If Hillary thinks she can unleash her husband, with his terrible record of women abuse, while playing the women’s card on me, she’s wrong!”
Well, Bill Clinton has a penchant for something. He had a successful presidency — with an ugly blot. “Sexism” isn’t the precise word for his predatory behavior toward women or his inexcusable relationship with a 22-year-old intern. Yet in the larger scheme of things, Bill Clinton’s conduct toward women is far worse than any of the offensive things that Trump has said.
Trump has smeared women because of their looks. Clinton has preyed on them, and in a workplace setting where he was by far the superior. That is uncomfortable for Clinton supporters but it is unavoidably true.
.... Ordinarily, I would argue that the sins of the husband should not be visited on the wife. ...
... But Hillary Clinton has made two moves that lead me, gulp, to agree with Trump on the “fair game” front. She is (smartly) using her husband as a campaign surrogate, and simultaneously (correctly) calling Trump sexist.
These moves open a dangerous door. ...
Now that it's opened, the Wall Street Journal's editorialists contend that there's no going back, because her willingness to open it previews the kind of presidential administration a Hillary Clinton victory would spawn:
... Mr. Trump is rude and crude, but in this case he is raising an issue that rightly bears on the 2016 election campaign and the prospect of a third Clinton term. Mrs. Clinton wants to use her gender both as a political sword and shield to win the White House. The purpose is to make male politicians less willing to take her on, while reinforcing her main and not-so-subtle campaign theme that it’s time to elect the first woman President.
So she and her allies will try to spin any criticism as sexist. ...
... no one in American politics better personifies a war on women than Mrs. Clinton’s husband. For readers too young to recall the 1990s, we aren’t merely referring to Trumpian gibes about female looks or “Mad Men” condescension. Mr. Clinton was a genuine sexual harasser in the classic definition of exploiting his power as a workplace superior, and the Clinton entourage worked hard to smear and discredit his many women accusers.
Start with “bimbo eruptions,” the phrase that Mr. Clinton’s Arkansas fixer Betsey Wright used to describe the women who had affairs with Bill. Gennifer Flowers almost derailed his primary campaign in 1992, until Hillary stood by her man on CBS’s “60 Minutes” and the media portrayed Ms. Flowers as a golddigger.
Many more would come forward, not least Paula Jones, an Arkansas state employee who testified that a state policeman working for then Governor Clinton invited her to Bill’s hotel room where he exposed himself and sexually propositioned her. Ms. Jones filed a sexual-harassment lawsuit and Mr. Clinton lied under oath, resulting in his impeachment.
... When news of that affair came to light, the Clintons also waged war on her reputation.
... when her (Mrs. Clinton's) own access to political power was at stake, she dismissed the women and defended her husband.
We rehearse all this not merely to reinforce Mr. Trump’s claims of a Clinton double standard. The point relates to the standards that would prevail in another Clinton Presidency.
If Mrs. Clinton is going to play the gender and sexism cards, she has to acknlowledge and answer for her self-evident role as her sexual predator husband's defender and enabler. A liberal columnist and a usually conservative editorial board agree. Mrs. Clinton's knee-jerk media defenders like Don Lemon have thus been ideologically surrounded by irrefutable logic. Henceforth, the pushback against any attempt by Team Clinton and her press apparatchiks to go to their worn-out playbook in smearing others should be fierce, and should cite the now-clear agreement among people across the ideological divide.
Cross-posted at BizzyBlog.com.

domain: news


4. Alchemilla glomerulans Buser, Bull. Herb. Boissier. 1(app. 2): 30. 1893.
Clustered lady's mantle, alchémille à glomérules
Alchemilla obtusa Buser; A. obtusa var. comosa Brenner; A. pseudomicans Böcher; A. vulgaris Linnaeus var. comosa (Brenner) Fernald & Wiegand
Plants medium-sized, grass green or glaucous, often becoming reddish orange when young changing to dark brownish especially on margins of leaves and flowers (young flowers are yellowish), ˂often coarse, 30–40 cm˃. Stems appressed-hairy throughout (hairs becoming looser and ± ascending distally). Leaves: stipules translucent to pale green, appearing brownish upon drying; ˂petiole thickly, usually densely appressed-hairy throughout, rarely glabrous or sparsely hairy (on spring leaves)˃; blade reniform to orbiculate, 7–9-lobed, margins undulate, basal sinuses narrow, middle lobes equal to longer than their half-widths; incisions absent; teeth: sometimes proximal sides at least slightly connivent, slightly concave near apex, slightly asymmetric, apex subobtuse to acute, abaxial surface with nerves hairy throughout, internerve regions ± hairy throughout, adaxial ˂light to grass green, sometimes glaucous, margins and folds usually turning reddish orange˃, sparsely to densely appressed-hairy throughout or only on folds. Inflorescences: primary branches densely appressed- to ascending-hairy; ˂peduncles appressed- to ascending-hairy or glabrous˃. Pedicels mostly glabrous or some of the proximal hairy. Flowers: epicalyx bractlet lengths 0.5 times to almost equal to sepals (narrower); hypanthium glabrous or sparsely appressed-hairy (on proximalmost flowers). Achenes not exserted.
Flowering late Jun–Sep. Moist herb slopes, willow scrub; 0–500 m; Greenland; Nfld. and Labr. (Labr.), Que.; Europe.
In contrast to Alchemilla wichurae, A. glomerulans occurs throughout the southern (unglaciated) portion of Greenland.


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“No man is an island….” So wrote the poet John Donne four centuries ago. And while he meant the unity of humanity, the metaphor could equally apply to the interdependence of the various parts of the human body, including the mouth. According to recent scientific research, your mouth isn’t an “island” either.
Much of this research has focused on periodontal (gum) disease, an infection most often caused by bacterial plaque that triggers inflammation in the gum tissues. Although an important part of the body’s defenses, if the inflammation becomes chronic it can damage the gums and weaken their attachment to the teeth. Supporting bone may also deteriorate leading eventually to tooth loss.
Avoiding that outcome is good reason alone for treating and controlling gum disease. But there’s another reason—the possible effect the infection may have on the rest of the body, especially if you have one or more systemic health issues. It may be possible for bacteria to enter the bloodstream through the diseased gum tissues to affect other parts of the body or possibly make other inflammatory conditions worse.
One such condition is diabetes, a disease which affects nearly one person in ten. Normally the hormone insulin helps turn dietary sugars into energy for the body’s cells. But with diabetes either the body doesn’t produce enough insulin or the available insulin can’t metabolize sugar effectively. The disease can cause or complicate many other serious health situations.
There appears to be some links between diabetes and gum disease, including that they both fuel chronic inflammation. This may explain why diabetics with uncontrolled gum disease also often have poor blood sugar levels. Conversely, diabetics often have an exaggerated inflammatory response to gum disease bacteria compared to someone without diabetes.
The good news, though, is that bringing systemic diseases like diabetes under control may have a positive effect on the treatment of gum disease. It may also mean that properly treating gum disease could also help you manage not only diabetes, but also other conditions like cardiovascular disease, osteoporosis, or rheumatoid arthritis. Taking care of your teeth and gums may not only bring greater health to your mouth, but to the rest of your body as well.
If you would like more information on treating dental diseases like gum disease, please contact us or schedule an appointment for a consultation. You can also learn more about this topic by reading the Dear Doctor magazine article “Good Oral Health Leads to Better Health Overall.”
Some people are lucky — they never seem to have a mishap, dental or otherwise. But for the rest of us, accidents just happen sometimes. Take actor Jamie Foxx, for example. A few years ago, he actually had a dentist intentionally chip one of his teeth so he could portray a homeless man more realistically. But recently, he got a chipped tooth in the more conventional way… well, conventional in Hollywood, anyway. It happened while he was shooting the movie Sleepless with co-star Michelle Monaghan.
“Yeah, we were doing a scene and somehow the action cue got thrown off or I wasn't looking,” he told an interviewer. “But boom! She comes down the pike. And I could tell because all this right here [my teeth] are fake. So as soon as that hit, I could taste the little chalkiness, but we kept rolling.” Ouch! So what's the best way to repair a chipped tooth? The answer it: it all depends…
For natural teeth that have only a small chip or minor crack, cosmetic bonding is a quick and relatively easy solution. In this procedure, a tooth-colored composite resin, made of a plastic matrix with inorganic glass fillers, is applied directly to the tooth's surface and then hardened or “cured” by a special light. Bonding offers a good color match, but isn't recommended if a large portion of the tooth structure is missing. It's also less permanent than other types of restoration, but may last up to 10 years.
When more of the tooth is missing, a crown or dental veneer may be a better answer. Veneers are super strong, wafer-thin coverings that are placed over the entire front surface of the tooth. They are made in a lab from a model of your teeth, and applied in a separate procedure that may involve removal of some natural tooth material. They can cover moderate chips or cracks, and even correct problems with tooth color or spacing.
A crown is the next step up: It's a replacement for the entire visible portion of the tooth, and may be needed when there's extensive damage. Like veneers, crowns (or caps) are made from models of your bite, and require more than one office visit to place; sometimes a root canal may also be needed to save the natural tooth. However, crowns are strong, natural looking, and can last many years.
But what about teeth like Jamie's, which have already been restored? That's a little more complicated than repairing a natural tooth. If the chip is small, it may be possible to smooth it off with standard dental tools. Sometimes, bonding material can be applied, but it may not bond as well with a restoration as it will with a natural tooth; plus, the repaired restoration may not last as long as it should. That's why, in many cases, we will advise that the entire restoration be replaced — it's often the most predictable and long-lasting solution.
Oh, and one more piece of advice: Get a custom-made mouthguard — and use it! This relatively inexpensive device, made in our office from a model of your own teeth, can save you from a serious mishap… whether you're doing Hollywood action scenes, playing sports or just riding a bike. It's the best way to protect your smile from whatever's coming at it!
If you have questions about repairing chipped teeth, please contact us or schedule an appointment for a consultation. You can also learn more by reading the Dear Doctor magazine articles “Artistic Repair of Chipped Teeth With Composite Resin” and “Porcelain Veneers.”
Periodontal (gum) disease causes more than simple gum swelling—this bacterial infection can harm and destroy your teeth’s supporting structures, including the bone. Its aggressiveness sometimes requires equally aggressive treatment.
Gum disease usually begins with dental plaque, a thin film of bacteria and food particles on tooth and gum surfaces. Without proper oral hygiene plaque builds up with large populations of bacteria that can trigger an infection.
The growth of this disease is often “silent,” meaning it may initially show no symptoms. If it does, it will normally be reddened, swollen and/or bleeding gums, and sometimes pain. A loose tooth is often a late sign the disease has severely damaged the gum ligaments and supporting bone, making tooth loss a distinct possibility.
If you’re diagnosed with gum disease, there is one primary treatment strategy—remove all detected plaque and calculus (tartar) from tooth and gum surfaces. This can take several sessions because as the gums begin responding to treatment and are less inflamed, more plaque and calculus may be discovered.
Plaque removal can involve various techniques depending on the depth of the infection within the gums. For surfaces above or just below the gum line, we often use a technique called scaling: manually removing plaque and calculus with specialized instruments called scalers. If the infection has progressed well below the gum line we may also use root planing, a technique for “shaving” plaque from root surfaces.
Once infection reaches these deeper levels it’s often difficult to access. Getting to it may require a surgical procedure known as flap surgery. We make incisions in the gums to form what looks like the flap of an envelope. By retracting this “flap” we can then access the root area of the tooth. After thoroughly cleansing the area of infection, we can do regenerative procedures to regain lost attachment. Then we suture the flap of gum tissue back into place.
Whatever its stage of development, it’s important to begin treatment of gum disease as soon as it’s detected. The earlier we can arrest its spread, the less likely we’ll need to employ these more invasive procedures. If you see any signs of gum disease as mentioned before, contact us as soon as possible for a full examination.
If you would like more information on preventing and treating gum disease, please contact us or schedule an appointment for a consultation. You can also learn more about this topic by reading the Dear Doctor magazine article “Treating Difficult Areas of Periodontal Disease.”
If your child begins complaining of tooth pain without an accompanying fever or facial swelling, it’s likely not an emergency. Still, you should have us check it—and the sooner the better if the pain persists or keeps your child up at night. There are a number of possible causes, any of which if untreated could be detrimental to their dental health.
Before coming in, though, you can do a cursory check of your child’s mouth to see if you notice any abnormalities. The most common cause for a toothache is tooth decay, which you might be able to see evidence of in the form of cavities or brown spots on the tooth’s biting surfaces. If you notice swollen or reddened gums around a tooth, this could be a possible sign of a localized area of infection known as an abscess. You should also ask your child if they fell or were hit in the mouth and look for any signs of an injury.
If you don’t see anything unusual, there may be another cause—stuck food like popcorn or candy lodged and exerting painful pressure on the gum tissue or tooth. You may be able to intervene in this case: gently floss around the affected tooth to try to dislodge any food particles. The pain may ease if you’re able to remove any. Even so, if you see abnormalities in the mouth or the pain doesn’t subside, you should definitely plan to come in for an examination.
In the meantime, you can help ease discomfort with a child-appropriate dose of ibuprofen or acetaminophen. An ice pack against the outside jaw may also help, but be careful not to apply ice directly to the skin. And under no circumstances rub aspirin or other painkiller directly on the gums—like ice, these products can burn the skin. If these efforts don’t help you should try to see us the same day or first thing the next morning for advanced treatment.
The main thing is not to panic. Knowing what to look for and when to see us will help ensure your child’s tooth pain will be cared for promptly.
If you would like more information on handling dental issues with your child, please contact us or schedule an appointment for a consultation. You can also learn more about this topic by reading the Dear Doctor magazine article “A Child’s Toothache.”
Could your toothache be trying to tell you that you require root canal therapy?
What is a root canal? Why is my tooth hurting so much? Do I need to visit a dentist if I’m dealing with a toothache? These are just some of the most frequent questions our Westfield, IN, dentists Drs. Kenneth and Katie Krause hear. Find out more about root canal treatment, why it’s performed and when dental problems may be trying to tell you that you need to seek care.
What is a root canal?
This endodontic procedure is performed when a tooth’s dental pulp is damaged or infected. The dental pulp lies inside the tooth underneath the hard enamel and dentin layers. The pulp consists of connective tissue, nerves and blood vessels. While this structure is important for the development of the tooth, once the tooth has fully matured the dental pulp is no longer necessary for the tooth to remain healthy and strong.
Of course, if decay, direct trauma or an infection sets in and isn’t caught right away it can continue to spread until it reaches the dental pulp. As a result, the dental pulp becomes infected or inflamed. Once this happens the only option is to have the pulp removed in order to preserve the rest of the tooth.
Besides removing the pulp, our Westfield, IN, general dentists will also disinfect the inside of the tooth to remove any bacteria or pus that is present. Furthermore, we will also fill the root canals with a special material to prevent an infection from occurring in the future.
What are the symptoms of a damaged dental pulp?
If you are experiencing any of these issues it’s time to schedule a visit with us right away, as you could require root canal treatment:
- A toothache
- Pain that gets worse when chewing or biting down on the tooth
- Sudden tooth sensitivity (to hot or cold temperature)
- Swelling or tenderness in the gums around the tooth
- A pimple-like growth on the gums (known as an abscess)
What happens if I don’t get a root canal?
Once the dental pulp is inflamed or infected it needs to be removed to prevent bacteria from growing within the tooth. The sooner we treat the tooth the better. If you don’t seek care, this infection can lead to bone and tooth loss.
Don’t let dental problems get the better of your smile. Here at Krause Dental in Westfield, IN, we pride ourselves on providing expert and immediate dental care when you need it most. Call us right away if you are experiencing any dental symptoms.
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DB Lift Provides Fast, Safe Lifting Of Small Loads And Packages. Features Counterweighted Lifting Mechanism For Smooth, Quiet Operation.
Ideal for high-speed applications that require light-duty lifting of boxes, cartons, packages, totes, containers or cases.
Provides throughput of four loads per minute (based on 100 lb. load, 10′ vertical rise, 90 to 120 fpm horizontal conveying speed.)
Counterweighted lifting mechanism requires minimal maintenance. Lifting belt never needs lubricating.
Perfect for use in an automated system.
Saves space and handles loads that are often transported on an inclined conveyor.
Completely self-contained, self-supporting and economical. Moves loads to mezzanines, between floors or between conveyor levels.
Lifts up to 100 lb. live loads with carriage sizes up to 3′ x 4′. Vertical rise to 50′. Travel speeds from 60 fpm to 400 fpm.
Counterweighted design minimizes horsepower requirements, saves energy costs.
Optional variable frequency drive package ensures smooth acceleration and deceleration control in high-speed, automated systems.
Allows loading and unloading from three sides.
Durable, high-quality construction ensures safe, reliable, long-term performance. Standard full-height safety enclosure protects workers and materials.
Meets ANSI/ASME B20.1 code.


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Trace your ancestry
The information gathered here can help you trace your Norwegian ancestors, and how best to use The Digital Archives.
The first thing you should to do is collect as much information as possible about the people you want to research.
What name(s) did they use, when were they born, and where did they live?
You may not know this yourself, so talk with family, review old pictures and documents, and make notes of what you find.
Read more about genealogy in general here: Tracing your ancestry
The information you collect should be checked against historical sources, where you may find additional information.
Always be critical of source material. By this, we mean that you should assess whether the information comes from a trustworthy source and compare the sources with one another. Bygdebøker (Village books) can be a great help, and there are many genealogy sites on the Internet, but it is easy to draw false conclusions and mix people up. Always check if the information is correct in the written historical sources.
For Norwegian sources, you will find the most widely used historical sources in The Digital Archives. For genealogists, these are parish registries and censuses, but sources such as probate records and tax lists can also be useful.
Read more about the sources in the Digital Archive here: Explore digitized archive material
You can search for people or places in the search box on the frontpage of the Digital Archive. Try a search for Fridtjof Nansen:
The list will show the first hits found in the sources available in the Digital Archive. Not all hits will refer to the same person, and may encounter variations in spelling. Click in the list to look at the result and the source it originates in.
You can also try a search for Sofie Matilde Nilsen. This will return results for different people; the first one being the most relevant result with the whole name, while the others are only partial results.
You can also restrict a search by adding a date. A search for Fridtjof Nansen 1861, will return results associated with the year 1861 in addition to the name.
We also have an advanced search, which you can restrict by geographic location, time period and much more: Advanced Search
Tip! You can begin by searching for people you are sure were living ca. 1900 - 1910. We have censuses from both 1900 and 1910 available, where you will find almost everyone who lived in Norway at the time.
Transcriptions of sources in the digital archive must be faithful copies of the original source material. By that, we mean that we make them available "as is". We do not correct typing errors in the sources and we do not try to normalize the spelling of personal names or place names. We do not change birthdays in people's censuses that differ from what you will find for the same person in the baptismal protocol of the parish records. We do not correct the sources in relation to each other.
This makes it challenging to search, as the sources may contain mistakes and omissions. Trying to fix these could introduce new errors; for example, the changes of people's names would potentially disappear. It is you, the user, who is responsible for assessing what is "correct".
A source provides a snapshot of a situation, but not the complete picture. Building a family history is the task of the genealogical investigator, for which the source materials are merely means to an end.
In The Digital Archives, you will find that many of the sources pertaining to people date from ca. 1650 to ca. 1930. We have information about people before and after this period, but before 1650 there are few available sources. After 1930, we have few available sources due to privacy reasons.
The period between 1801 to 1910 is best covered, as we have nationwide censuses available for this entire period.
- Our Help Pages can be found here: Help pages
- We have a dedicated debate forum with thousands of participants and activity around the clock. The User's own forum is where users can help one another.
- Short list of expressions for property listings can be found here: Glossary of property
- How to trace your ancestors in Norway
Tips on other family history sites
- National Library
- Local libraries have local history collections
- There are teams and associations that can be most helpful. Examples can include [Family and Data] (http://www.disnorge.no) and Norwegian Family History Association (NSF), but there are many others. Please read the page Overview of History on Local History Wizard
- Words and expressions can be difficult to understand. There are several online dictionaries that can prove useful; for example: Your Family: Glossary of Families

domain: history


text:
The Qur’an, Islam’s holy book, plays a central role in the lives of Muslims and is considered the ultimate source of guidance for all aspects of life. Revealed to the Prophet Muhammad over a period of 23 years, the Qur’an is believed to be the word of Allah, conveyed through the angel Gabriel.
For Muslims, the Qur’an is more than just a book. It is a spiritual guide that provides direction, wisdom, and inspiration. Its teachings cover a wide range of topics, including faith, morality, social justice, family values, and personal conduct. Muslims strive to study and understand the Qur’an, seeking guidance from its verses to navigate through the challenges of life.
The Qur’an is written in Arabic, and its language is considered a miracle in itself. Muslims believe that the beauty and eloquence of the Arabic language used in the Qur’an reflects the divine nature of the text.
Muslims show great respect and reverence for the Qur’an. They handle the book with utmost care, keeping it elevated and clean. The recitation of the Qur’an is also an important practice in Islam, with many Muslims memorising the entire book or sections of it.
By understanding the role of the Qur’an, we can appreciate its significance in shaping the beliefs and practices of Muslims. It serves as a constant reminder of their relationship with Allah and guides them towards living a righteous and meaningful life.

domain: library


text:
Contact the Center
The Center for Global Citizenship (CGC) is located at 3672 West Pine Mall. The CGC includes occupant centers and offices housed in neighboring Des Peres Hall. Both buildings are easily recognizable by the array of international flags lining the rooftops. The nearest intersections to the CGC are Laclede Avenue and Grande Avenue and Laclede Avenue and South Spring Avenue.
Parking is available in the visitor section of the Laclede Garage or at meters along Laclede Avenue.
The Center for Global Citizenship is accessible from the front entrance on West Pine Mall adjacent to the clock tower. Des Peres Hall also offers a rear door entrance to the building from the Gonzaga parking lot.
Schedule an Event
To schedule an event in the Auditorium or Atrium contact Event Services at 314-977-6338 or firstname.lastname@example.org.
To schedule an event in the Seminar Room, or any conference room in the Center for Global Citizenship or in Des Peres Hall, contact Kathy Michael at 314-977-9326 or email@example.com.
For information about activities of the Center for Global Citizenship, or for information on how to collaborate with the CGC and its occupant groups, please contact Kathy Michael at 314-977-93276 or firstname.lastname@example.org.
Center for Global Citizenship
3672 West Pine Mall
St. Louis, MO 63108
Map: Center for Global Citizenship

domain: geography


This past Sunday, the Royal Academy hosted a free, family-friendly workshop that combined 70,000 Lego bricks and the imagination of its participants. The idea was to inspire the public to think about architecture, to coincide with the RA's current exhibition on Richard Rogers.
We went along expecting to see familiar London buildings in Lego-form. Instead we were greeted with unique creations from fertile minds. While most buildings were constructed by children, the parents also got involved. Some buildings were taller than us, and some were precariously balanced (which proved to be a challenge to the organisers when placed aside a mock Thames river). Towards the end of the three-hour event, we overheard one of the organisers say "This is no longer child's play".
The creations are intended to stay with the exhibition until 13 October, but you may want to get there sooner than later just in case the dreaded "Kidzilla" decides to walk through the city leaving carnage behind.


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Kharkov is a city situated in the north-eastern part of Ukraine. It is the second largest city after Kiev and the first capital of the country. It is still referred to like this by its habitants who are proud of their city.
First of all Kharkov is an industrial city. There are many factories and plants there. In this respect a flow of people head to Kharkov in search of jobs and career growth.
It is also a city of fun and entertainment. One can never be bored either in the daytine or at night. Cinemas, cafes, restaurants, disco clubs get alive when darkness goes down. Among the most popular entertainment establishments it is possible to name Misto, Bolero and restaurant of traditional Ukrainian cuisine-Sloboda. Nevertheless Kharkov has preserved all historical monuments and architecture.
Sumskaya is the longest street, lined up with shops and fashinable boutiques. Pushkinskays Street is the oldest one and is considered to be the home of the first Kharkov habitants.
The life is always in full swing here and never slows down even if it seems like this. Parks and recreational zones are the most favourite destinations for students and young people, coming from all over Ukraine to get education. They say it is a city of students, it is a city of youth, energy and restless stream of life to be more corect.
Science and Education
Kharkiv is one of the most prolific centres of higher education and research of Eastern Europe. The city has 13 national universities and numerous professional, technical and private higher education institutions, offering its students a wide range of disciplines. Kharkiv National University, National Technical University “KhPI”, Kharkiv National Aerospace University “KhAI” are the leading universities in Ukraine. A total number of 150,000 students attend the universities and other institutions of higher education in Kharkiv. About 9,000 foreign students from 96 countries study in the city. More than 17,000 faculty and research staff are employed in the institutions of higher education in Kharkiv.
The city has a high concentration of research institutions, which are independent or loosely connected with the universities. Among them are three national science centres: Kharkіv Institute of Physics and Technology, Institute of Metrology, Institute for Experimental and Clinical Veterinary Medicine and 20 national research institutions of the National Academy of Science of Ukraine.


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Flying to your family vacation destination is often the quickest, easiest way to travel, but flying with children takes extra planning. If you haven’t flown with your kids before, or if you’re looking for ways to make your next trip safer and smoother, you’ll enjoy these sites, which are full of air travel tips for families…Read More
Are you planning on flying with your dog, cat, bird, or other pet? You’ll need to check the latest TSA regulations and the current rules for the airline you’ll be flying on, then plan for potty breaks, snacks, water… The pre-flight to-do list can get overwhelming, but don’t worry. There’s plenty of information available to guide you through the process and keep your pet safe and happy. Here are some of the best resources on the web for airline travel with pets…Read More
Should I rent out my vacation home? If you’re asking yourself this question, you’re definitely not alone. According to a recent study by the National Association of Realtors, 86% of vacation home buyers plan to rent out their property to travelers. There’s certainly a lot to consider when opening up your home to guests, but the benefits can be significant. As you contemplate how to proceed, here are some great reasons to rent out your second home:Read More
As more and more travelers discover the benefits of staying in vacation rental homes, alternative accommodations are becoming increasingly popular for families looking for more space and better value. As a vacation rental owner, you have an opportunity to attract this huge — and growing! — group of travelers. But how do you set your home apart?Read More
The Evolve Network currently has over 250 vacation rental homes — and we’re always growing! See if you can guess which destinations have been booked most often by our travelers! It’s no surprise that our most popular vacation spots are full of sunshine… Is your favorite destination in our top 5?Read More
1. What is your role at Evolve?
Throughout the past year, I’ve had the opportunity to wear many different hats! From speaking with travelers and homeowners, to bookkeeping and office management, to marketing and recruiting, I’ve been involved with a variety of projects at Evolve. Most recently, I have shifted my main focus to recruiting, as we’re looking for smart, enthusiastic individuals to join our amazing team!Read More

domain: travel