A wide range of techniques is available to assess tumor cell proliferation such as calculating mitotic figures in stained tissue segments, flow cytometric analysis to determine the proportion of cells being in the S phase of the cell cycle, examination of thymidine-labeling index, proliferating cell nuclear antigen (PCNA), or cyclins E and D
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Ki-67 is a prognostic parameter in breast cancer patients: results of a large populatio... - 0 views
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Ki-67 is a nuclear protein being associated with cellular proliferation and was originally identified by Gerdes et al.
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Ki-67 nuclear antigen is expressed in certain phases of the cell cycle namely S, G1, G2, and M phases, but is nonexisting in G0
- ...11 more annotations...
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Ki-67 is also expressed at low levels (<3 % of cells) in ER-negative cells, but not in ER-positive cells
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A meta-analysis involving 12,155 patients demonstrated that the Ki-67 positivity confers a higher risk of recurrence and a worse survival rate in patients with early breast cancer.
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higher tumor stages and higher nodal status were associated with higher Ki-67 quartiles indicating that the more aggressive the tumor is the higher is the percentage of cells positively stained for Ki-67
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Previous studies were able to demonstrate that a prognostic model, the IHC 4 score, using ER, PR, HER2, and Ki-67 provides similar prognostic information to that in the 21-gene Genomic Health recurrence score
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ER status has been largely identified as being inversely correlated with Ki-67, with the higher rates of ER positivity shown in the lowest proliferating tumors
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Ki-67-labeling index was associated with larger tumors, higher tumor grade, peritumoral vascular invasion, and HER-2 positivity
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Late Disseminated Lyme Disease: Associated Pathology and Spirochete Persistence Post-Tr... - 0 views
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In this study, we have demonstrated microscopic pathology ranging from minimal to moderate in multiple different tissues previously reported to be involved with LD, including the nervous system (central and peripheral), heart, skeletal muscle, joint-associated tissues, and urinary bladder 12 to 13 months following tick-inoculation of rhesus macaques by Bb strain B31
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Based on histomorphology, inflammation consisted predominantly of lymphocytes and plasma cells, with rare scattered histiocytes
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in rare instances, morphologically intact spirochetes were observed in inflamed brain and heart tissue sections from doxycycline-treated animals
- ...41 more annotations...
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colocalization of the Bb 23S rRNA probe was not observed in any of the sections of experimental inoculated animals shown to harbor rare persistent spirochetes (Supplemental Figure S1). Previous in vitro work has shown large decreases in Bb rRNA levels when in a stationary phase of growth despite the majority of spirochetes remaining viable
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The possibility that the spirochetes were intact but dead also exists, though this may be unlikely given the precedence for viable but non-cultivable B. burgdorferi post-treatment
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The doxycycline dose utilized in this study (5mg/kg) was based on a previous pharmacokinetic analysis of oral doxycycline in rhesus macaques proven to be comparable to levels achieved in humans and was meant to mimic treatment of disseminated LD
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In addition to the brain of two treated animals, rare morphologically intact spirochetes immunoreactive to OspA were observed in the heart of one treated animal
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Although we did not measure the doxycycline levels in the cerebrospinal fluid, they have been found to be 12% to 15% of the amount measured in serum
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We and others have demonstrated the development of a drug-tolerant persister population when B. burgdorferi are treated with antibiotics in vitro
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The adoption of a dormant or slow-growing phenotype likely allows the spirochetes to survive and re-grow following removal of antibiotic
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The basic premise that antibiotic tolerance may be an adaptation of the sophisticated stringent response required for the enzootic cycle by the spirochetes is described in a recent review as well
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Although current IDSA guidelines recommend intravenous ceftriaxone (2g daily for 30 days) over oral doxycycline for treatment of neuroborreliosis, a randomized clinical trial failed to show any enhanced efficacy of I.V. penicillin G to oral doxycycline for treatment of Lyme neuroborreliosis (no treatment failures were reported in this study of 54 patients).
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we can speculate that the minimal to moderate inflammation that was observed, especially within the CNS and PNS can, in part, explain the breadth of symptoms experienced by late stage Lyme disease patients, such as cognitive impairment and neuralgia.
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Erythema migrans, the clinical hallmark of early localized Lyme disease, was observed in one of the rhesus macaques from this study.
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In 2014, a trailblazing study in mice demonstrated a dramatic decline in B. burgdorferi DNA in the tissues for up to eight months after antibiotic treatment followed by the resurgence of B. burgdorferi growth 12 months after treatment
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This study provides evidence that the slow-growing spirochetes which persist after treatment, but are not cultivable in standard growth media may remain viable.
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The first well-documented indication of Lyme disease (LD) in the United States occurred in the early 1970s
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Lyme disease is now known to be caused by multiple closely related genospecies classified within the Bb sensu lato complex, representing the most common tick-borne human disease in the Northern Hemisphere
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approximately 30,000 physician-reported cases occur annually in the United States, the annual incidence has been estimated to be 10-fold higher by the Centers for Disease Control and Prevention.6
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Current antibiotic therapy guidelines outlined by the Infectious Disease Society of America (IDSA) are successful in the treatment of LD for the majority of LD patients, especially when administered early in disease immediately following identification of erythema migrans (EM)
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host-adapted spirochetes that persist in the tissues, probably in small numbers, inaccessible or impervious to antibiotic
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Experimental studies on immunocompetent mice, dogs, and rhesus macaques have provided evidence for the persistence of Bb spirochetes subsequent to antibiotic treatment in the form of residual spirochetes detected within tissue by IFA and PCR, and recovered by xenodiagnoses
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half (five) of the NHP received antibiotic treatment, consisting of 5 mg/kg oral doxycycline twice per day.
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Peripheral nerves contained minimal to moderate lymphoplasmacytic inflammation with a predilection for collagen-rich epineurium and perivascular spaces
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Minimal to mild lymphoplasmacytic inflammation of either the myocardial interstitium (Figure 2Figure 2A), pericardium (Figure 2Figure 2B), or combination therein was observed in 60% of NHPs
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A single morphologically intact spirochete, as indicated by positive red immunofluorescence (Figure 2Figure 2C), was observed in the myocardium of one treated animal
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three animals exhibited minimal to mild lymphoplasmacytic inflammation affecting joint-associated structures
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Multiple randomized placebo-controlled studies which evaluated sustained antimicrobial therapy concluded that there is no benefit in alleviating patients’ symptoms and indicated that long-term antibiotic therapy may even be detrimental to patients due to potential associated complications (ie, catheter infection and/or clostridial colitis)
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Printinginn - 0 views
www.printinginn.com
Booklets Bookmarks Box Printing Brochures Business Cards Calendars CD Jackets Flyers Labels Letterheads Post Posters Rack Stickers Tickets.
shared by Benton Smith on 30 Oct 12
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Printinginn.com is a one-stop solution for all your printing needs. Printinginn provides full color printing in different styles, sizes and shapes using materials of your choice. We are specialized in Booklets, Bookmarks, Box Printing, Brochures, Business Cards, CD Jackets, Flyers, Labels, Letterheads, Post Cards, Posters, Rack Cards, Stickers and many more. We use the best printing methods to achieve best printing results and thus can print your jobs using a vast number of custom options.
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Sugar Content of Popular Sweetened Beverages Based on Objective Laboratory Analysis: Fo... - 0 views
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Arch Gen Psychiatry -- Abstract: Trajectories of Depression Severity in Clinical Trials... - 0 views
archpsyc.ama-assn.org/...1227
depression psychiatry SSRI therapy treatment cymbalta duloxetine non-resonders
shared by Nathan Goodyear on 10 Dec 11
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Neurobehavioural effects of developmental toxicity : The Lancet Neurology - 0 views
www.thelancet.com/...abstract
flourine toxins environmental brain neurology ADD ADHD autism ASD pediatrics children
shared by Nathan Goodyear on 11 Mar 14
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new study out of the Lancet labels Flouride as neurotoxicant, along with lead, methyl mercury, PCBs, arsenic, toluene and others. This is not a political issue and needs to be reviewed scientifically. These toxicants impair neurodevelopment and may be one reason for the rapidly rising conditions associated: i.e. ADD, ADHD, autism...
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PLOS ONE: Vitamin C: Intravenous Use by Complementary and Alternative Medicine Practiti... - 0 views
www.plosone.org/...journal.pone.0011414
IV vitamin C vitamin C intravenous alternative medicine complementary alternative
shared by Nathan Goodyear on 29 Sep 13
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Proton pump inhibitors decrease diversity in gut microbiome, increase risk for complica... - 0 views
www.sciencedaily.com/...141125074656.htm
PPIs proton pump inhibitors gut flora gut microbiome gut microbiota gut health biodiversity diversity
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O2*− and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Su... - 0 views
www.ncbi.nlm.nih.gov/...PMC5497844
Cancer "vitamin C" "IV vitamin H2O2 Fe ascorbate ascorbic acid redox
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Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic... - 0 views
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Recent reports indicate that a certain ROS concentration is required for high-dose vitamin C to induce cytotoxicity in cancer cells.
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In this study, we report that PAA is efficacious in killing MM cells in vitro and in vivo models, which generated levels of 20–40 mM ascorbate and 500 nM ascorbyl radicals after intraperitoneal administration of 4 g ascorbate per kilogram of body weight (Chen et al., 2008Chen et al., 2008), in xenograft MM mice
- ...33 more annotations...
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These data suggest that PAA may show a therapeutic advantage to blood cancers vs solid tumors because of the communication between tumor cells and blood plasma
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These results strongly suggest that the mechanism of PAA killing of MM cells is indeed iron-dependent
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These results suggest that PAA administration in SMM may be able to prevent progression to symtomatic MM
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A recent study by Yun and colleagues demonstrated that vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH, but spares normal cells
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RAS family genes show the most frequent mutations in MM. KRAS, NRAS and BRAF are mutated in 22%, 20% and 7% of MM samples
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the disease stage rather than the mutation of RAS and/or BRAF is the major predictive factor for PAA sensitivity in MM treatment
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Other molecular mechanisms including ATP depletion and ATM-AMPK signaling have been reported to explain PAA-induced cell death
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Our findings complement reported studies and further address the mechanism of action using clinical samples in which we observed that PAA killed tumor cells with high iron content, suggesting that iron might be the initiator of PAA cytotoxicity
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combination of PAA with standard therapeutic drugs, such as melphalan, may significantly reduce the dose of melphalan needed
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Combined treatment of reduced dose melphalan with PAA achieved a significantly longer progression-free survival than the same dose of melphalan alone.
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These data also suggest that the bone marrow suppression induced by high-dose melphalan can be ameliorated by the combination of PAA with lower dose of melphalan because of the lack of toxicity of PAA on normal cells with low iron content.
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In MM preclinical and clinical studies, ascorbate was used as an adjunct drug and showed controversial results (Harvey et al., 2009, Perrone et al., 2009, Held et al., 2013, Sharma et al., 2012, Nakano et al., 2011, Takahashi, 2010, Sharma et al., 2009, Qazilbash et al., 2008). However, none of these tests used pharmacological doses of ascorbate and intravenous administration
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Cameron and Pauling reported that high doses of vitamin C increased survival of patients with cancer
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pharmacologically dosed ascorbic acid (PAA) 50–100 g (Chen et al., 2008, Padayatty et al., 2004, Hoffer et al., 2008, Padayatty et al., 2006, Welsh et al., 2013), administered intravenously, has potent anti-cancer activity and its role as anti-cancer therapy is being studied at the University of Iowa and in other centers
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In the presence of catalytic metal ions like iron, PAA administered intravenously exerts pro-oxidant effects leading to the formation of highly reactive oxygen species (ROS), resulting in cell death
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The survival of CD138+ cells in vitro was significantly decreased following PAA treatment in all 9 MM
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In contrast, no significant change of cell viability was observed in CD138− BM cells from the same patients
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the combination of melphalan plus PAA showed greater tumor burden reduction than each drug alone, suggesting a synergistic activity between these two drugs
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adding deferoxamine (DFO), an iron chelator, to OCI-MY5 cells before PAA treatment was also sufficient to prevent PAA-induced cellular death
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PAA by reacting with LIP and generating ROS induces mitochondria-mediated apoptosis in which AIF1 cleavage is important for cell death.
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microRNA Expression in Ethnic Specific Early Stage Breast Cancer: an Integration and Co... - 0 views
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dysregulated miRNA could be involved in tumor cell proliferation and growth as well as cell cycle progression
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The upregulated miR-183 in our samples was predicted to be responsible for the decrease in expression of the BTG1 mRNA whose protein is involved in cell cycle arrest and apoptosis in breast cancer cells18.
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nother molecule related to cell proliferation that was over-expressed in our data and suggested as a target of downregulated miR-376c is AURKA
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the over-expression of miR-183 and miR-21 in Lebanese breast cancer tissues is consistent with downregulation of two important tumor suppressor predicted targets: AKAP12 whose protein regulates cellular adhesion dynamics by controlling cytoskeletal architecture, cell migration, and mitogenic signaling20; and LATS2 whose protein causes cell cycle arrest
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dysregulation in cancer particularly in breast cancer highlights their importance in tumor development
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mRNA-miRNA integration analysis of early breast cancer revealed a potential role of miRNA in increasing cellular proliferation and progression, and decreasing invasion and migration
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most of the miRNA dysregulated in Lebanese breast cancer patients are similar to those dysregulated in American patients, differences in miRNA expression exist and could be attributed either to the patients’ age at diagnosis or to ethnic variation in miRNA epigenetic regulation and sequence variation of pre-miRNA
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microRNA (miRNA) are small non-coding 18–25 nucleotide RNA molecules currently being studied as potential diagnostic, prognostic and therapeutic biomarkers for cancer and other diseases
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Extensive research on these post-transcriptional modulators has proven that they are deregulated in breast cancerous tissues and even in biological fluids from breast cancer patients
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Tumor regionalization after surgery: Roles of the tumor microenvironment and neutrophil... - 0 views
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tumor surgery must be carefully considered because the risk of metastasis could be increased by the surgical procedure.
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surgery results in a serious wound that disrupts the structural barrier preventing the outspreading of cancer cells, change the properties of the cancer cells and stromal cells remaining in the tumor microenvironment, or impairs the host defense systems against cancers
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After the primary tumor is surgically removed, the metastases can start to grow vigorously via neoangiogenesis because the circulating inhibitors disappear
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infection and inflammation during the postoperative period have been reported to increase the risk of cancer recurrence in patients
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Surgeons have long suspected that surgery, even if it is a necessary step in cancer treatment, facilitates cancer metastasis
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Even externally palpitating tumors for diagnosis could increase the numbers of CTCs in skin cancer and breast cancer
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In addition to glucocorticoids, during stimulation of the HPA axis, the catecholamine hormones epinephrine and norepinephrine are released from the adrenal medulla
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NK cell suppression may be attributed to increased levels of catecholamines as well as glucocorticoids
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In mice bearing a primary tumor, it was observed that the removal of the primary tumor facilitated the growth of highly vascularized metastases
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second phase of tumor recurrence and metastasis, which are newly acquired events, rather than just outcomes of incomplete treatment.
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formation of neutrophil extracellular traps (NETs), which are large extracellular complexes composed of chromatin and cytoplasmic/granular proteins1
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Once activated, neutrophils produce intracellular precursors by using DNA, histones, and granular and cytoplasmic proteins and then spread the mature form of NETs out around themselves
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neutrophil elastase, myeloperoxidase, cathepsin G, proteinase 3, lactoferrin, gelatinase, lysozyme C, calprotectin, neutrophil defensins, and cathelicidins
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NETs are present in a variety of cancers, such as lung cancer, colon cancer, ovarian cancer, and leukemia
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the proliferative cytokines TGFβ and IL-10 and the angiogenic factor VEGF are representative of neutrophil-derived tissue repair proteins.
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when neutrophils are excessively stimulated, they produce excess NETs, thereby leading to pathological consequences
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local invasion, intravasation into the blood or lymphatic vessels, escape from the immune system, anchoring to capillaries in target organs, extravasation into the organs, transformation from dormant cells to proliferating cells, colonization to micrometastases, and growth to macrometastases
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NETs and platelets wrap CTCs, which protects them from attack by immune cells and shearing force by blood flow
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After metastasizing to distant tissues, tumor cells are often found to remain dormant for a period of time and unexpectedly regrow late
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NET-associated proteases NE and MMP-9 were found to be responsible for the reactivation of dormant cancer cells
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LeanBiome™ (Official) | Get Save UpTo $540 Today Only! - 0 views
usleanbiome.com
leanbiome us lean biome usa uk buy get does work discount 2022 australia legit weight loss bioma customer reviews review canada website ireland product
shared by fitspresso on 27 Sep 23
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LeanBiome™ (Official) | Get Save UpTo $540 Today Only! usleanbiome.com LeanBiome™ Hurry Up! Offer Expires in: 00 HOUR 29 MINUTE 59 SECOND LeanBiome Attention! Get Special 84% Discount Today Faster fat burning and weight loss Healthy cholesterol and sugar levels Higher energy levels Regular price: $129 Only for: 39$ What Is LeanBiome? LeanBiome Lean for Good is a weight loss dietary supplement derived from scientifically researched ingredients and comprehensively developed to help people achieve sustainable weight control. The formula comes in a capsule format that is easy to take and is made with natural ingredients from plants and other sources to achieve its goals. The main ingredient in LeanBiome is piperine, which has been found to affect the body's ability to absorb micronutrients and other compounds more effectively. LeanBiome is a dietary supplement that claims to help weight management. It contains 100% natural ingredients that support healthy weight loss. It does not interfere with any natural process making it safe for use. It ranks among the top weight loss supplements that claim to provide a permanent solution. LeanBiome is made by a company named Lean for Good. It is made with natural and research-backed ingredients that help you lose excess fat without hassles. It is sold in capsule form. The company assures the composition is GMO, gluten, and soy-free. As for manufacturing standards, you need not fret. The company makes the supplement in a facility certified by the FDA. How Does LeanBiome Work? The starting period of the LeanBiome program includes a detoxification process that effectively removes any accumulated ree radicals, toxins, fand oxidative stress. This cleansing enables improved blood circulation, setting the stage for the body to initiate its own fat-burning mechanisms. To enhance metabolic activity, introducing the lean bacteria contained in LeanBiome to your gut microbiome is a beneficial approach. This activation triggers r
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An Open-Label Pilot Study to Assess the Efficacy and Safety of Virgin Coconut Oil in Re... - 0 views
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The Ketogenic Diet and Sport: A Possible Marriage? : Exercise and Sport Sciences Reviews - 0 views
journals.lww.com/..._and_Sport___A_Possible.8.aspx
nutrition diet ketogenic ketogenic diet sports athletes exercise sports medicine
shared by Nathan Goodyear on 16 Nov 16
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It is important to note that, although the blood level of glucose drops, it still remains at a physiological level (23), which is maintained through gluconeogenesis involving glucogenic amino acids and also glycerol released from triglycerides
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“physiological ketosis” where KB levels may rise to 7 to 8 mmol L-1 (but without any pH change). In “pathological diabetic ketoacidosis,” on the other hand, ketonemia can exceed 20 mmol L-1 and also cause lowering of blood pH
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in the initial phase of KD, about 16% of glucose comes from glycerol (released from triglyceride hydrolysis) and the bulk (60–65 g) from proteins via gluconeogenesis (proteins may be of either dietary or endogenous origin
- ...5 more annotations...
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The importance of glycerol as a glucose source increases progressively during ketosis; in fact, glycerol passes from supplying 16% of total glucose to an average of 60% after many days (>7 d) of complete fasting (from 38% in lean individual to 79% in the obese).
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The possible reasons for the effectiveness of KD for weight loss may be listed as follows, in order of evidence, strongest first: Figure 3Image Tools 1. Appetite reduction: protein satiety, effects on appetite-related hormones such as ghrelin, and possibly a sort of direct appetite-blocking effect of KB 2. Reduced lipogenesis and increased fat oxidation 3. A reduction in respiratory quotient may indicate a greater metabolic efficiency in fat oxidation 4. A thermic effect of proteins and increased energy usage by gluconeogenesis
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all data regarding biochemical and molecular mechanisms suggest that it is very difficult to increase muscle mass during a KD; use of which really should be limited to the few days immediately before competition in bodybuilding.
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a long-term KD can interfere with some muscle hypertrophy mechanisms and this could be counterproductive if the aim of the athlete is to gain muscle mass
Perfect Body Building Supplements - 3 views
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A randomized, open-label, crossover study ... [Menopause. 2007 Nov-Dec] - PubMed - NCBI - 0 views
www.ncbi.nlm.nih.gov/...17507833
BHRT HRT estrogen oral transdermal therapy treatment hormones TBG thyroid liver metabolism
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BMC Complementary and Alternative Medicine | Full text | An open label pilot study to e... - 0 views
www.biomedcentral.com/...475
black spanish radish radish alternative medicine nutrition detoxification
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Normalization of testosterone level is associated with reduced incidence of myocardial ... - 0 views
eurheartj.oxfordjournals.org/...2706
low T low Testosterone Testosterone Testosterone therapy mortality MI stroke heart men male hormones
shared by Nathan Goodyear on 18 Jan 16
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In this study of men with low TT levels and without prior MI or stroke, normalization of TT levels using TRT is associated with lower all-cause mortality, fewer MIs, and ischaemic strokes.
- ...9 more annotations...
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It can be postulated that the beneficial effect of normal T levels on adipose tissue, insulin sensitivity, and lipid profiles or by its anti-inflammatory and anticoagulant properties, as reported by other investigators, might have contributed to our findings
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Recent FDA analyses suggest that currently only half of the men on TRT had been diagnosed with hypogonadism
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men without a history of previous MI or stroke who have low TT levels, TRT might be associated with decreased risks of MI, ischaemic stroke, and all-cause mortality in long-term follow-up
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TRT should aim for doses resulting in normalization of TT level as this was shown to be associated with reduction in adverse CV events