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fitspresso

https://www.sightcare-co.com/ - 0 views

www.sightcare-co.com

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shared by fitspresso on 27 Sep 23 - No Cached
  • fitspresso on 27 Sep 23
     
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Nathan Goodyear

Exposure to the Functional Bacterial Amyloid Protein Curli Enhances Alpha-Synuclein Agg... - 0 views

www.nature.com/srep34477

neurodegenerative disease amyloid alzheimer's disease Parkinson's disease gut gut flora gut microbiome gut microbiota gut-brain

shared by Nathan Goodyear on 06 Oct 16 - No Cached
  • Our work suggests that protein misfolding and immune activation in neurodegenerative disorders are triggered through cross-seeding by exposure to exogenous microbial amyloids in the nose, mouth and gut.
  • Streptococcus mutans, Staphlococcus aureus, Salmonella enterica, Mycobacterium tuberculosis and others
  • Gene homologs encoding curli were recently determined also in four phyla: Bacteroidetes, Proteobacteria, Firmicutes, and Thermodesulfobacteria
  • ...8 more annotations...
  • changes in the gut microbiota induced by antibiotics alter neuroinflammation and amyloid deposition in a mouse model of AD
  • Our data suggest that amyloid proteins in the microbiota are involved in the origination and maintenance of neurodegenerative disease.
  • exposure to bacteria producing a functional extracellular amyloid protein enhances aggregation of AS in brain neurons in aged rats and in muscle cells in nematodes
  • AS aggregates seed aggregation of tau
  • involvement of the vagus nerve in PD
  • microgliosis, astrogliosis and enhanced expression of IL-6, TLR2 and TNF in the brain following curli exposure suggest the occurrence of an enhanced local sterile inflammatory response to AS in the brain.
  • the immune system in both AD and PD have now been extensively established
  • TLR2 activation through exposure to bacterial amyloid is pathogenic
  • Nathan Goodyear on 06 Oct 16
     
    Gut bacteria may play crucial role in systemic inflammation that leads to Alzheimer's and Parkinson's disease.  These amyloid production bacteria trigger systemic inflammation that leads to microglia activation and amyloid in the brain.   More establishment of the gut-brain connection.  
Nathan Goodyear

Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as a p... - 0 views

www.pnas.org/...13604.full

IV vitamin C cancer ascorbic acid vitamin C H2O2 GPX glutathione Perioxidase

shared by Nathan Goodyear on 09 Feb 11 - Cached
  • Taken together, these data indicate that ascorbate at concentrations achieved only by i.v. administration may be a pro-drug for formation of H2O2, and that blood can be a delivery system of the pro-drug to tissues.
  • These findings give plausibility to i.v. ascorbic acid in cancer treatment, and have unexpected implications for treatment of infections where H2O2 may be beneficial
  • pharmacologic concentrations of ascorbate killed cancer but not normal cells, that cell death was dependent only on extracellular but not intracellular ascorbate, and that killing was dependent on extracellular hydrogen peroxide (H2O2) formation with ascorbate radical as an intermediate
  • ...48 more annotations...
  • Our data show that ascorbic acid selectively killed cancer but not normal cells, using concentrations that could only be achieved by i.v. administration
  • Ascorbate-mediated cell death was due to protein-dependent extracellular H2O2 generation, via ascorbate radical formation from ascorbate as the electron donor. Like glucose, when ascorbate is infused i.v., the resulting pharmacologic concentrations should distribute rapidly in the extracellular water space (42). We showed that such pharmacologic ascorbate concentrations in media, as a surrogate for extracellular fluid, generated ascorbate radical and H2O2. In contrast, the same pharmacologic ascorbate concentrations in whole blood generated little detectable ascorbate radical and no detectable H2O2. These findings can be accounted for by efficient and redundant H2O2 catabolic pathways in whole blood (e.g., catalase and glutathione peroxidase) relative to those in media or extracellular fluid
  • ascorbic acid administered i.v. in pharmacologic concentrations may serve as a pro-drug for H2O2 delivery to the extracellular milieu
  • H2O2 generated in blood is normally removed by catalase and glutathione peroxidase within red blood cells, with internal glutathione providing reducing equivalents
  • The electron source for glutathione is NADPH from the pentose shunt, via glucose-6-phosphate dehydrogenase. If activity of this enzyme is diminished, the predicted outcome is impaired H2O2 removal causing intravascular hemolysis, the observed clinical finding.
    • Nathan Goodyear
      Nathan Goodyear on 05 Mar 18
       
      The mechansism here is inadequate recycling of GSH due to lack of G6PD, build up of intracellular H2O2 and RBC lysis--hemolysis.
  • Only recently has it been understood that the discordant clinical findings can be explained by previously unrecognized fundamental pharmacokinetics properties of ascorbate
  • Intracellular transport of ascorbate is tightly controlled in relation to extracellular concentration
  • Intravenous ascorbate infusion is expected to drastically change extracellular but not intracellular concentrations
  • For i.v. ascorbate to be clinically useful in killing cancer cells, pharmacologic but not physiologic extracellular concentrations should be effective, independent of intracellular ascorbate concentrations.
    • Nathan Goodyear
      Nathan Goodyear on 05 Mar 18
       
      accumulation of extracellular vitamin C is the effect.
  • It is unknown why ascorbate, via H2O2, killed some cancer cells but not normal cells.
  • There was no correlation with ascorbate-induced cell death and glutathione, catalase activity, or glutathione peroxidase activity.
  • H2O2, as the product of pharmacologic ascorbate concentrations, has potential therapeutic uses in addition to cancer treatment, especially in infections
  • Neutrophils generate H2O2 from superoxide,
  • i.v. ascorbate is effective in some viral infections
  • H2O2 is toxic to hepatitis C
  • Use of ascorbate as an H2O2-delivery system against sensitive pathogens, viral or bacterial, has substantial clinical implications that deserve rapid exploration.
  • Recent pharmacokinetics studies in men and women show that 10 g of ascorbate given i.v. is expected to produce plasma concentrations of nearly 6 mM, which are >25-fold higher than those concentrations from the same oral dose
  • As much as a 70-fold difference in plasma concentrations is expected between oral and i.v. administration,
  • Complementary and alternative medicine practitioners worldwide currently use ascorbate i.v. in some patients, in part because there is no apparent harm
  • Human Burkitt's lymphoma cells
  • We first investigated whether ascorbate in pharmacologic concentrations selectively affected the survival of cancer cells by studying nine cancer cell lines
  • Clinical pharmacokinetics analyses show that pharmacologic concentrations of plasma ascorbate, from 0.3 to 15 mM, are achievable only from i.v. administration
  • plasma ascorbate concentrations from maximum possible oral doses cannot exceed 0.22 mM because of limited intestinal absorption
  • For five of the nine cancer cell lines, ascorbate concentrations causing a 50% decrease in cell survival (EC50 values) were less than 5 mM, a concentration easily achievable from i.v. infusion
  • All tested normal cells were insensitive to 20 mM ascorbate.
    • Nathan Goodyear
      Nathan Goodyear on 05 Mar 18
       
      meaning safe.
  • Lymphoma cells were selected because of their sensitivity to ascorbate
  • As ascorbate concentration increased, the pattern of death changed from apoptosis to pyknosis/necrosis, a pattern suggestive of H2O2-mediated cell death
  • Apoptosis occurred by 6 h after exposure, and cell death by pyknosis was ≈90% at 14 h after exposure
    • Nathan Goodyear
      Nathan Goodyear on 05 Mar 18
       
      work continued beyond the IVC therapy itself
  • In contrast to lymphoma cells, there was little or no killing of normal lymphocytes and monocytes by ascorbate
  • Ascorbate is transported into cells as such by sodium-dependent transporters, whereas dehydroascorbic acid is transported into cells by glucose transporters and then immediately reduced internally to ascorbate
  • Whether or not intracellular ascorbate was preloaded, extracellular ascorbate induced the same amount and type of death.
  • extracellular ascorbate in pharmacologic concentrations mediates death of lymphoma cells by apoptosis and pyknosis/necrosis, independently of intracellular ascorbate.
  • H2O2 as the effector species mediating pharmacologic ascorbate-induced cell death
  • Superoxide dismutase was not protective
  • Because these data implicated H2O2 in cell killing, we added H2O2 to lymphoma cells and studied death patterns using nuclear staining (19, 28). The death patterns found with exogenous H2O2 exposure were similar to those found with ascorbate
  • For both ascorbate and H2O2, death changed from apoptosis to pyknosis/necrosis as concentrations increased
  • Sensitivity to direct exposure to H2O2 was greater in lymphoma cells compared with normal lymphocytes and normal monocytes
  • There was no association between the EC50 for ascorbate-mediated cell death and intracellular glutathione concentrations, catalase activity, or glutathione peroxidase activity
  • H2O2 generation was dependent on time, ascorbate concentration, and the presence of trace amounts of serum in media
  • ascorbate radical is a surrogate marker for H2O2 formation.
  • whatever H2O2 is generated should be removed by glutathione peroxidase and catalase within red blood cells, because H2O2 is membrane permeable
  • The data are consistent with the hypothesis that ascorbate in pharmacologic concentrations is a pro-drug for H2O2 generation in the extracellular milieu but not in blood.
  • The occurrence of one predicted complication, oxalate kidney stones, is controversial
  • In patients with glucose-6-phosphate dehydrogenase deficiency, i.v. ascorbate is contraindicated because it causes intravascular hemolysis
  • ascorbate at pharmacologic concentrations in blood is a pro-drug for H2O2 delivery to tissues.
  • ascorbate, an electron-donor in such reactions, ironically initiates pro-oxidant chemistry and H2O2 formation
  • data here showed that ascorbate initiated H2O2 formation extracellularly, but H2O2 targets could be either intracellular or extracellular, because H2O2 is membrane permeant
    • Nathan Goodyear
      Nathan Goodyear on 05 Mar 18
       
      the conversion of ascorbate to H2O2 occurs extracellular
  • More than 100 patients have been described, presumably without glucose-6-phosphate dehydrogenase deficiency, who received 10 g or more of i.v. ascorbate with no reported adverse effects other than tumor lysis
  • Nathan Goodyear on 09 Feb 11
     
    IV vitamin C benefits cancer patients
Nathan Goodyear

Interleukin‐2 enhances the natural killer cell response to Herceptin‐coated H... - 1 views

onlinelibrary.wiley.com/...%3AAID-IMMU3016%3E3.0.CO%3B2-J

IL-2 breast cancer cancer NK cells HER-2 immunotherapy

shared by Nathan Goodyear on 18 Jun 18 - No Cached
  • administration of low‐dose IL‐2 results in expansion of a CD3– / CD56+ NK cell population in patients with advanced cancer
  • approximately 20 % will overexpress theHer2 / neu proto‐oncogene
  • In breast cancer, Her2 / neu overexpression is associated with a worse histologicalgrade, decreased relapse‐free and overall survival periods, and altered sensitivity to chemotherapeutic regimens
  • ...17 more annotations...
  • NK cells are large granular lymphocytes that comprise approximately 10 % of circulating lymphocytes
  • all human NK cells express the CD56 antigen
  • treatment with various concentrations of IL‐2 in vivo may induce distinct functions within the NK cell compartment and, therefore, may have profound effects on NK cell‐mediated cytotoxicity
  • CD56bright
  • CD56dim
  • We show here that ADCC conducted by NK cells in vitro is enhanced by IL‐2 activation and is critically dependent on interactions between FcγRIII on NK cells and Herceptin‐coated tumor targets
  • administration of low‐dose IL‐2 to patients results in the marked expansion of a CD56+ population of immune effectors with the ability to lyse antibody‐coated cancer targets
  • NK cells represented only 7 % of lymphocytes prior to therapy but comprised over 50 % of the population after 10 weeks of low‐dose IL‐2
  • These data suggest that the enhanced ADCC seen following the expansion of NK cells with low‐dose IL‐2 is likely due to an increase in the overall number of NK cells
  • co‐administration of IL‐2 with rhu4D5 mAb will enhance activation of NK cell effector functions
  • Stimulation of NK cells with IL‐2 resulted in a significant increase in the lysis of rhu4D5‐coated targets
  • We have shown that costimulation with IL‐2 plus rhu4D5 results in significant production of IFN‐γ by NK cells with concomitant up‐regulation of cell‐surface activation and adhesion molecules
  • It has been previously demonstrated that continuous low‐dose IL‐2 can expand a CD56+ lymphocyte population, and we have now shown that this cell population is a potent mediator of ADCC against rhu4D5 mAb‐coated Her2 / neu+ targets
  • These results suggest that administration of low‐dose IL‐2 can be used to expand NK cell numbers, while higher doses may be used to enhance their cytolytic capacity in the setting of mAb therapy
  • we have demonstrated that NK cell lysis of Her2 / neu+ breast cancer cell lines in the presence of rhu4D5 mAb is markedly enhanced following stimulation with IL‐2
  • we have presented evidence that administration of low‐dose IL‐2 in vivo results in the expansion of a potent NK cell effector population
  • Our experiments suggest that NK cells costimulated with IL‐2 and immobilized IgG can secrete potent immunomodulatory cytokines which may serve to potentiate the anti‐tumor immune response.
  • Nathan Goodyear on 18 Jun 18
     
    low dose IL-2 found to expand NK levels in conjuction in with herceptin in HER-2 positive breast cancer cell lines.
Ciara Usher

My One and Only Comfy Craftmatic Bed - 1 views

I used to have restless nights, I cannot sleep soundly. And I thought it was because I kept on thinking of my boyfriend. But I was wrong. I found out that the reason I cannot sleep because I was no...

Craftmatic adjustable beds

started by Ciara Usher on 17 Mar 11 no follow-up yet
Ciara Usher

My One and Only Comfy Craftmatic Bed - 1 views

I used to have restless nights, I cannot sleep soundly. And I thought it was because I kept on thinking of my boyfriend. But I was wrong. I found out that the reason I cannot sleep because I was no...

Craftmatic adjustable beds

started by Ciara Usher on 06 Apr 11 no follow-up yet
Nathan Goodyear

Testosterone and benign prostatic hyperplasia Jarvis TR, Chughtai B, Kaplan SA, - Asian... - 0 views

www.ajandrology.com/preprintarticle.asp

Testosterone BPH low T low Testosterone prostate cancer men male hormone hormones

shared by Nathan Goodyear on 01 Dec 14 - No Cached
  • The prevalence of hypogonadism (often defined as serum testosterone < 300 ng dl−1 ) ranges from 6% [10] to as high as 38%
  • The process of BPH, however, continues as men age and despite the fact their serum testosterone decreases
  • Liu et al. [12] demonstrated that in a group of older males (mean age 59.8 years) that there was not a significant correlation of serum testosterone levels (total, free or bioavailable) with either prostate volume or International Prostate Symptom Score (IPSS)
  • ...11 more annotations...
  • in eugonadal men, studies have demonstrated that the prostate can increase in volume by approximately 12%
  • There seems to be little doubt that the treatment with testosterone of a young hypogonadal male leads to significant growth of the prostate
  • Behre et al. [22] demonstrated increased prostate volume and prostate-specific antigen (PSA) levels in hypogonadal men
  • Most studies, however, have shown no effect of exogenous androgens on PSA or prostate volume for older hypogonadal males
  • saturation model
  • They argue that the prostate is relatively insensitive to changes in androgen concentration at normal levels or in mild hypogonadism because the AR is saturated by androgens and therefore maximal androgen-AR binding is achieved. Conversely, the prostate is very sensitive to changes in androgen levels when testosterone is low
  • visceral obesity (one of the most significant components of metabolic syndrome) is associated with prostate volume and influences prostate growth during TRT.
  • This hypothesis of inflammation induced LUTS is also argued to be a mechanism for improvement of LUTS with PDE5I
  • The concept, therefore, that treatment with TRT of hypogonadal males with metabolic syndrome might lead to improvement/stabilization of their LUTS, appears to be confirmed in recent work by Francomano et al.
  • There was also an improvement in components of the patient's metabolic syndrome (such as BMI, waist circumference, hemoglobin A1c [HbA1c], insulin sensitivity, and lipid profile) as well as inflammatory markers and C-reactive protein.
  • They concluded that TRT was safe in this group of men, and hypothesize that TRT mitigates the pro-inflammatory factors associated with metabolic syndrome.
  • Nathan Goodyear on 01 Dec 14
     
    Authors review the literature behind Testosterone and BPH.  The authors highlight the 4 proposed theories behind BPH: Testosterone, Estrogen, inflammation, and metabolic.   The conclusion is mixed: pointing out that no high level of evidence exists on either side of the debate of Testosterone and BPH.
fitspresso

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www.fitspresso-co.com

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shared by fitspresso on 27 Sep 23 - No Cached
  • fitspresso on 27 Sep 23
     
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fitspresso

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shared by fitspresso on 27 Sep 23 - No Cached
  • fitspresso on 27 Sep 23
     
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Stanley Bishop

The Reliable Sleep Apnea Home Test - 1 views

Because I used to snore hard, my wife insisted that I should see a doctor to make sure that this snoring problem will not lead to a more serious health concern. However, going to a doctor is the la...

started by Stanley Bishop on 17 Oct 12 no follow-up yet
Edgar Anderson

Gaining Back My Good Health - 1 views

Due to my very hectic schedule at work there were several times that I skipped some meals and ate mostly canned foods or those that have preservatives. I thought it would not affect my health beca...

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started by Edgar Anderson on 30 Aug 13 no follow-up yet
Meredith Blige

Aid For Snoring Problem - 2 views

My wife would always complain about my snoring a lot. Before, I thought it was just because I was exhausted from work, but as time goes by, I am already afraid my snoring is getting worse, that eve...

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started by Meredith Blige on 19 Jul 11 no follow-up yet
Ciara Usher

My Craftmatic Bed Helped Me Sleep - 1 views

Funny thing, when I graduated from college and went straight to work, I started to have restless nights. At first, I thought it was because I kept on thinking of my work and the stress it carried. ...

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started by Ciara Usher on 27 Oct 11 no follow-up yet
Nathan Goodyear

Frontiers | Microbiome-Derived Lipopolysaccharide Enriched in the Perinuclear Region of... - 0 views

journal.frontiersin.org/...full

LPS lipopolysaccharides Alzheimer's disease brain inflammation

shared by Nathan Goodyear on 23 Sep 17 - No Cached
  • lipopolysaccharides (LPS), either alone or in combination, have indicated that when compared, bacterial LPSs exhibit the strongest induction of pro-inflammatory signaling in human neuronal–glial cells in primary coculture of any single inducer, and different LPS extracts from different gastrointestinal (GI)-tract resident Gram-negative bacteria appeared to have different pro-inflammatory potential
  • powerful inducer of the NF-κB
  • In both neocortex and hippocampus, LPS has been detected to range from a ~7- to ~21-fold increase abundance in AD brain
  • ...15 more annotations...
  • Major Gram-negative bacilli of the human GI-tract, such as the abundant B. fragilis and Escherichia coli (E. coli), are capable of discharging a remarkably complex assortment of pro-inflammatory neurotoxins
  • (i) bacterial amyloids (10, 21); (ii) endotoxins and exotoxins (5, 12); (iii) LPS (12, 18); and (iv) small non-coding RNAs (sncRNAs)
  • integral components of the outer leaflet of the outer membrane of Gram-negative bacteria, LPS
  • LPS, the major molecular component of the outer membrane of Gram-negative bacteria normally serves as a physical barrier providing the bacteria protection from its surroundings
  • LPS is also recognized by the immune system as a marker for the detection of bacterial pathogen invasion and responsible for the development of inflammatory response is perhaps the most potent stimulator and trigger of inflammation known
  • AD-affected brains have remarkably large loads of bacterial-derived toxins compared to controls. The transfer of noxious, pro-inflammatory molecules from the GI-tract microbiome to the CNS may be increasingly important during the course of aging when both the GI-tract and blood–brain barriers become significantly more permeable
  • first evidence of a perinuclear association of LPS with AD brain cell nuclei
  • LPS-mediated stimulation of chronic inflammation, beta-amyloid accumulation, and episodic memory decline in murine models of AD (39, 40) and a biophysical association of LPS with amyloid deposits and blood vessels in human AD patients
  • Strong adherence of LPS to the nuclear periphery has recently been shown to inhibit nuclear maturation and function that may impair or block export of mRNA signals from brain cell nuclei, a highly active organelle with extremely high rates of transcription, mRNA processing, and export into the cytoplasm
  • LPS may be further injurious to the nuclear membrane just as LPS contributes to cerebrovascular endothelial cell membrane injury
  • high intake of dietary fiber is a strong inhibitor of B. fragilis abundance and proliferation in the intact human GI-tract and as such is a potent inhibitor of the neurotoxic B. fragilis-derived amyloids, LPS, enterotoxins, and sncRNAs.
  • GI-tract microbiome-derived LPS may be an important initiator and/or significant contributor to inflammatory degeneration in the AD CNS
  • LPS has been recently localized to the same anatomical regions involved in AD-type neuropathology
  • a known pro-inflammatory transcription factor complex that triggers the expression of pathogenic pathways involved in neurodegenerative inflammation
  • pro-inflammatory amyloids, endo- and exotoxins, LPSs, and sncRNAs but also serve as potent sources of membrane-disrupting agents
  • Nathan Goodyear on 23 Sep 17
     
    LPS links gut to inflammation in Alzheimer's disease
Nathan Goodyear

Relationship between endogenous testosterone and cardiovascular risk in early postmenop... - 0 views

www.metabolismjournal.com/...abstract

testosterone women high elevated CRP inflammation BMI obesity overweight post-menopausal CVD

shared by Nathan Goodyear on 10 May 12 - No Cached
  • Body mass index and waist circumference were significantly higher in the group with testosterone levels
  • Median CRP levels were greater in the group with higher testosterone level
  • ET-1 levels were also higher in women with greater testosterone levels
  • ...2 more annotations...
  • An association of testosterone with CRP (r = 0.416, P = .004) and ET-1 (r = 0.323, P = .031) was observed
  • Testosterone was also associated with waist circumference and blood pressure (P = .001)
  • Nathan Goodyear on 10 May 12
     
    testosterone associated with elevated CRP, increase BMI, and increased waist circumference in early, post-menopausal women.
stretchmark treatment

My Effective Stretch Mark Cream - 3 views

I am very depressed this past few days because I thought I will never get rid of this stretch marks on my thighs, I am still at my teenage years and I cannot even enjoy going out with my friends to...

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started by stretchmark treatment on 23 Mar 12 no follow-up yet
Nathan Goodyear

Normal Flora - Medical Microbiology - NCBI Bookshelf - 0 views

www.ncbi.nlm.nih.gov/...NBK7617

flora gut flora gut microbiome gut microbiota

shared by Nathan Goodyear on 05 May 15 - No Cached
  • Concentrations of 109 to 1011 bacteria/g of contents are frequently found in human colon
  • more than 400 species have been identified
  • 95 to 99 percent belong to anaerobic genera such as Bacteroides, Bifidobacterium, Eubacterium, Peptostreptococcus, and Clostridium
  • ...2 more annotations...
  • hese genera proliferate, occupy most available niches, and produce metabolic waste products such as acetic, butyric, and lactic acids
  • Anaerobic bacteria can then deconjugate bile acids in this region and bind available vitamin B12 so that the vitamin and fats are malabsorbed
  • Nathan Goodyear on 05 May 15
     
    normal flora of the body
alexabert

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HELLO For my donation project, you may be the person I need. In short, my name is Alexandrea BERTUZZI, of Italian origin, but under medical observation in France. I suffer from a serious illness wh...

started by alexabert on 27 Jun 20 no follow-up yet
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I have been working straight for a year now and yet I have not given myself the chance to relax and unwind. My friend told me about Shantai Wellness Spa, a day spa in Adelaide that is using only na...

started by Day Spa Adelaide on 18 Dec 12 no follow-up yet
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I have been working straight for a year now and yet I have not given myself the chance to relax and unwind. My friend told me about Shantai Wellness Spa, a day spa in Adelaide that is using only na...

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