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Nathan Goodyear

The Contribution of Cytotoxic Chemotherapy to 5-year Survival in Adult Malignancies | C... - 0 views

  • In this group, the 5-year survivalrateduesolelytocytotoxicchemotherapywas14%
  • There is also no convincing evidence that usingregimens with newer and more expensive drugs are anymore beneficial than the regimens used in the 1970s
  • two systematic reviews of chemotherapy inrecurrent or metastatic breast cancer have not been able toshow any survival benefit
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  • The five most common adult malignancies (colorectal, breast, prostate, melanoma and lung cancer)
  • n breast cancer, the optimal regimen(s) for cytotoxicchemotherapy in recurrent/metastatic disease are still notdefined, despite over 30 years of ‘research’ and a plethora of RCTs since the original Cooper regimen was published in1969
  • The five most ‘chemo-sensitive’ cancers,namely testis, Hodgkin’s disease and non-Hodgkin’s lym- phoma, cervix and ovary
  • only 13 out of the 22 malignancies evaluated showed any improvement in 5-year survival, and theimprovement was greater than 10% in only three of those13 malignancies
  • the contribution of curative and adjuvant cytotoxic chemotherapy to 5-year survival in adults is 2.3% in Australia and 2.1% in the USA
  • a benefit of less than 2.5% is likely to be applicable in other developed countries
  •   Overview The Contribution o
  • the benefit of cytotoxic chemotherapy may have been overestimated for cancers of oesophagus, stomach,rectum and brain.
  • this reflects the presentation of results as a ‘reduction in risk’ rather than asan absolute survival benefit[89,90]and by exaggerating theresponse rates by including ‘stable disease’
  • recent studies have documented impaired cognitive function inwomen receiving adjuvant treatment for breast cancer
  • the 5-year survival rate due solely to cytotoxicchemotherapy was 1.6%
  • the value of palliative chemotherapy has beenquestioned
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    Incredibly low impact of cytotoxic chemotherapy despite its wide spread utilization.  This article referenced cost yet did not evaluate the cost of cytotoxic side effect.  The question to answer: is Cytotoxic chemotherapy a valid treatment, at all, for the majority of cancers.
Nathan Goodyear

Histamine dihydrochloride and low-dose interleukin-2 as post-consolidation im... - 0 views

  • IL-2 is a central T cell-derived cytokine, which induces NK cell and T cell proliferation, differentiation and activation, and also stim-ulates the production of secondary immunostimulatory cytokines
  • combination of histamine and IL-2 thus triggers efficient NK cell-mediated killing of several types of leukemic cells, including freshly recovered human AML blasts
  • histamine improves the effects of IL-2 on T cell activation
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  • principal action of histamine is to protect cytotoxic lymphocytes from myeloid-cell-induced inactivation, thus improving the efficiency of the T and NK cell stimulation achieved by IL-2
  • random-ized Phase II study of patients with renal cell carcinoma further support the suggestion that the combination of HDC and IL-2 improves lymphocyte functions
  • HDC improves the effectiveness of IL-2-induced T and NK cell activation in cancer patients, as predicted in preclinical models
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    histamine dihydrochloride enhances immune effects of NK cells in IL02 therapy; specifically in this analysis in AML, the histamin prevented inactivation of the IL-2 activated NK cells.
Nathan Goodyear

Comparative Studies of the Estrogen Receptors β and α and the Androgen Recept... - 0 views

  • ER-β is predominately immunolocalized in basal cells and to a lesser extent in stromal cells of the morphologically normal human prostate
  • ER-α is detected in stromal cells and rarely in basal cells of the normal gland
  • AR was predominately localized in the nuclei of differentiated secretory cells and variably in basal cells of the normal acinar/duct unit as well as in stromal cells
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  • Hall and colleagues44 have reported that ER-β functions as a transdominant inhibitor of ER-α transcription and that it acts to decrease overall cellular sensitivity to estradiol
  • The expression of ER-β was diminished in high-grade dysplasias when compared to normal glands and lower grade lesions.
  • The transition from normal to low/moderate dysplastic glands in the peripheral zone was marked by the appearance of ER-β homogeneously immunostained nuclei in secretory as well as basal cells with no changes in the localization of the other receptors.
  • proliferative signals mediated by AR in basal cells or by ER-α and AR in stromal cells may be opposed by the purported growth-inhibitory action of ER-β25, 26, 27, 28 localized in basal cells.
  • The diminution of ER-β expression in high-grade dysplasias and grade 4/5 cancers may be therefore related to the alteration of DNA methylation pattern in CpG islands of the promoter, resulting in down-regulation of the receptor at the transcriptional level
  • based on the proposed anti-proliferative function of the receptor,25, 26, 27, 28 the presence of ER-β in secretory cells of low/moderate-grade lesions may represent a transient abortive attempt to counter growth of these cells
  • the attrition of receptor-positive basal cells in the high-grade dysplasias may signify a continuing loss of growth inhibitory function mediated by ER-β in these precursor lesions
  • Our findings in prostate therefore differ from those reported for human colon cancer in which Folley and colleagues48 demonstrated that a selective loss of ER-β protein but not receptor message expression occurs in these neoplasms
  • Our findings therefore differed from those of Bonkhoff and colleagues33 who found immunostaining for the receptor in high-grade dysplasias and grade 4/5 carcinomas. Using in situ hybridization these authors also reported that a high percentage of dysplasias and carcinomas in their study contained cells that expressed ER-α message
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    Very nice study.  The authors looked at normal prostate, early disease and late stage prostate cancer.  The authors found that ER beta expression, as a general rule, was lost as progression occurred to the high-grade dysplasias and grad 4/5 carcinomas of the prostate.  Early low/moderate dysplasia was associated with an increase in ER beta--the authors propose that this was due to an attempt of the basal epithelium to counter the paracrine effect of ER alpha.   In contrast, androgen receptors appeared to be equally expressed across all.
wheelchairindia9

Pediatric Wheelchair KM 7501 - 0 views

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    Ergonomically designed wheelchair not only for the patients but also for the assistants, both of them are considered users of this wheelchair. WheelCare has been designed to prevent work injury to the assistants by redesigned the handle, seat, hanger, rear pedals and front pedals, make them adjustable and easier to use. Tube-shaped structure allows the users to install extensional gears depends on the different needs. Ergonomic Wheelchairs with a body contouring S-Shaped seat frame and contoured armrests provides the user with all day comfort and ultimate mobility. And since this wheelchair is designed around the human body, less likely to need a seat cushion or other device to help make the wheelchair more comfortable. Ergonomics is really about using bodies safely and efficiently, in a way which doesn't strain the tissues. A way which is comfortable, While working, cooking, driving, creating or other work. Karma Wheelchair KM 7501: Karma Healthcare KM 7501 Pediatric Wheelchair is a manual wheelchair for children. It's ergonomically antelope horn-shaped handle makes it easy to steer and push the chair, and vertical footrest allow legs to be placed in the correct position. One-piece footplate increases stability. The wheelchair has a great look with a bright color and modern style. Karma Healthcare Wheelchair KM 7501 Features: Karma Healthcare Wheelchair KM-7501 Paediatric Wheelchair offers here-we-go handle Caring footrest Seat width: 11" or 13.5" Ultra lightweight and compact Outward extended front wheels 6" solid caster and 14" solid rear wheel Maximum user weight: 60Kg One Year Warranty Karma Wheelchair KM 7501 Measurements: Width 11" 13.5" Front/Rear Wheels 6" to 14" 6" to 14" Seat Width 28cm 34cm Seat Depth 30cm 30cm Overall Width 45cm 51cm Overall Collapsed Width 34cm 34cm Armrest Height 18cm 18cm Overall Length 70W 70W Seat Height 39cm 39cm Backrest Height 36cm 36cm Overall Height 102cm 102cm Weight 9.3kg 9.3kg Karma Ergo
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Ergonomic Wheelchair - 0 views

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    Lightweight Ergonomic Wheelchair is designed to cradle patients in comfort while reducing risk of pressure sores, relieving pressure, dispersing weight evenly and improving stability. The Ergo Lite Wheelchair is easy to lift and its small size makes it ideal for travel. Weighing only 19.8 lbs., the chair is easy to store and transport. The chair folds down the middle like a standard wheelchair and the backrest also folds down to make the wheelchair even more compact. Also features companion brakes located on handles for added safety and comfort. Ergonomic Wheelchairs are ultra lightweight and have a supportive seating system to provide pressure relief and anti-slippage giving the user excellent stability and posture support. . Better Ergonomic wheelchair for Comfort: Sit for any length of time in a fixed position in a traditional transport chair and it will feel how painful bad ergonomics can be. It is fully reclined 25° angle, which minimizes slumping and sliding. And because of this can be easily adjusted with the push of a button, it can change positions frequently over time, reducing the chance of secondary conditions that may include pressure sores. Designed to Fit Almost Everyone: It is one of the most extensively researched seat profiles specifically design to accommodate users ranging in size from small women to large men, with the greatest amount of comfort and proper posture/spinal support. The Karman wheelchairs are exceptional in both their function and style. With comfort built right into the frame of a wheelchair eliminating the need for a "thick cushion" to add comfort, S-Shape seat allows the wheelchair to be "ergonomically correct" putting into a seating position and comfort conforming to natural body's curves. These chairs are built for comfort and quality to stand the test of time. Ergonomic Wheelchair is Right: Ergonomic Wheelchair is designed for users who will spend a large amount of time in the chair. This wheelchair'
Nathan Goodyear

Inborn-like errors of metabolism are determinants of breast cancer risk, clinical respo... - 0 views

  • We now recognize that human cancers evolve in an environment of metabolic stress. Rapidly proliferating tumor cells deprived of adequate oxygen, nutrients, hormones and growth factors up-regulate pathways that address these deficiencies to overcome hypoxia (HIF), vascular insufficiency (VEGF), growth factor deprivation (EGFR, HER2) and the loss of hormonal support (ER, PR, AR) all to enhance survival and proliferation
  • RAS, PI3K, TP53 and MYC
  • The results suggest that breast cancer could be preceded by systemic subclinical disturbances in glucose-insulin homeostasis characterized by mild, likely asymptomatic, IEM-like biochemical changes
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  • The process would include variable periods of hyperinsulinemia with the consequent systemic MYC activation of glycolysis, glutaminolysis, structural lipidogenesis and further exacerbation of hypoglycemia, the result of MYC's known role as an inhibitor of liver gluconeogenesis
  • The metabolic changes we describe in breast cancer arise in concert with IEM-like changes in oxidative phosphorylation as detected by increased values of the ratio lactate/pyruvate (Supplementary Table 2A, 2B) characteristic of Ox/Phos deficiency [25]. In our study, 76% (70/92) of the European breast cancer patients had lactate/pyruvate ratios values higher than the normal value of 25.8
  • four-fold higher frequency of cancer (including breast) in patients with energy metabolism disorders
  • growing recognition that cancer cells differ from their normal counterparts in their use of nutrients, synthesis of biomolecules and generation of energy
  • glutamine concentrations in the cancer patients were reduced to nearly 1/8 of the levels observed in the normal population
  • blood concentrations of aspartate (p = 1.7e-67, FDR = 8.3e-67) (Figure ​(Figure1E)1E) and glutamate (p = 6.4e-96, FDR = 6.2e-95) (Figure ​(Figure1F)1F) were nearly 10 fold higher than the normal ranges of 0–5 μM/L and 40 μM/L, respectively
  • glutamine consumption associated with parallel increases in glutamate and aspartate (Figure ​(Figure1A1A red arrows) is considered a hallmark of MYC-driven “glutaminolysis”
  • Gln/Glu ratio inversely correlates with i- late stage metabolic syndrome and with ii- increased chance of death
  • changes in glutamine consumption, reflected by the Gln/Glu ratio could provide a metabolic link between breast cancer initiation and diabetes, reflective of a systemic metabolic reprogramming from glucose to glutamine as the preferred source of precursors for biosynthetic reactions and cellular energy
  • lower Gln/Glu ratios inversely correlated with insulin resistance and the risk of diabetes
  • the metabolic dependencies of cancer characterized by excessive glycolysis, glutaminolysis and malignant lipidogenesis, previously considered a consequence of local tumor DNA aberration [23] could, instead, represent a systemic biochemical aberration that predates and very likely promotes tumorigenesis
  • these metabolic disturbances would be expected to remain extant after therapeutic interventions
  • accumulation of very long chain acylcarnitines such as C14:1-OH (p = 0.0, FDR = 0.0), C16 (p = 0.0, FDR = 0.0), C18 (p = 0.0, FDR = 0.0) and C18:1 (p = 1.73e-322, FDR = 1.16-321) and lipids containing VLCFA (lysoPC a C28:0) (p = 1.14-e95, FDR = 1.65e-95) in the blood of breast and colon cancer patients
  • Among the most powerful metabolic equations for MYC-activation is that which links the widely used MYC-driven desaturation marker ratio of SFA/MUFA to the MYC glutaminolysis-associated ratio of (Asp/Gln)
  • liver dysfunction shares many features with both IEM and cancer suggesting a role for hepatic dysfunction in carcinogenesis
  • cancer “conscripts” the human genome to meet its needs under conditions of systemic metabolic stress
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    Breast cancer is a metabolic disease.  Now, where have I heard that cancer is a metabolic disease?
hohanbogdan

Obosit mereu - 0 views

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started by hohanbogdan on 19 Jan 18 no follow-up yet
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Reclining Commode Wheelchair - 0 views

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    wheelchair category (standard, transport, power, etc.) could be classified as a reclining wheelchairs, since the product class is built around one key feature: the capability to adjust the backrest and/or footrest into a reclined position. This feature is especially important to users who find it difficult or impossible to sit in a fully upright position, and users who sleep in their chairs frequently. For those that are looking for a more portable chair, however, products from this category may not be a great fit. When compared with a similar, non-reclining chair, a reclining wheelchair tends to weigh more and - unlike other manual models - manual wheelchairs that recline typically aren't foldable. Some people use special wheelchairs to distribute pressure and thus reduce the risk of skin sores. These chairs also increase comfort and sitting tolerance. One type of chair, called "tilt in space," changes a person's orientation while maintaining fixed hip, knee, and ankle angles. The whole seat, in effect, tilts. The other chair option is called a recline system, which basically changes the seat-to-back angle, flattening out the back of the chair and in some cases raising the legs to form a flat surface. Different Types Of Reclining Wheelchairs: Reclining Wheelchair 902 GC Reclining Wheelchair 609 GC Karma Aurora 4 Reclining Wheelchair Karma Reclining Wheelchair KM 5000 Karma VIP 515 Wheelchair Reclining Wheelchair 902 GC: Reclining Wheelchair 902 GC is one of the basic models of a Reclining Wheelchair which helps transfer to bed to wheelchair easily and comes with head and neck support and Calf support for added comfort. Reclining Wheelchair 902 GC Features: The chair boast of movable armrest and elevating footrest. A well padded thigh support helps the user thigh's during reclining. The front and the rear wheels are designed and placed in such a way so as to support the users weight during reclining. The Pneumatic rear wheels help the movement
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Toilet Wheelchair - 0 views

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    Commode chairs are best suited for people who cannot use a regular toilet. The chairs enable patients who have limited mobility due to an accident or any medical condition to use the toilet with ease. The chair allows the patient to use the toilet without causing discomfort to the legs and back. The chair can be used by people who are restricted to a bed or wheelchair. A commode chair is a useful mobility for people of any age who are recovering from injury or surgery. The chair offers a reasonable level of independence to the user; a handy device to be presented to someone who needs it and for whom care. Commode Wheelchairs which are specially designed for aged and physically challenged people. These wheelchairs can be used for indoor toilet purposes. Fabricated using quality raw material, these wheelchairs are suitable for domestic and hospital purpose. There are two types for handicapped and disability product like Commode Wheelchair- Commode Wheelchair Rainbow 6 Commode Wheelchair Rainbow 7 Commode Wheelchair Rainbow 6: Karma commode wheelchair rainbow 6 comes with lot of exiting features for elderly or physically challenged person who want commode in wheelchair. Karma Rainbow 6 has single seat with center cut commode having cushion cover on top and removable pan or plastic commode seat with pot. Commode Wheelchair Rainbow 6 Features: Frame Material : M.S.Chrome Plated Single Seat with center cut commode Both Option Available In Single Seat Plastic Commode Seat With Pot. Cushioned Top Cover Square Pan Commode Pan Removable Pan Commode Wheelchair Rainbow 6 Measurements: Frame Style : Foldable Open Position Wheel To Wheel Width In : 26" (Inches) Seat Width : 18" (Inches) Total Width in Closing Position : 11" (Inches) Rear Wheel Size : 24" (Inches) Front Wheel Size : 8" (Inches) Seat to Floor Height : 19" (Inches) Seat Depth : 18" (Inches) Total Height : 34" (Inches) Max User Weight Capacity : 110 (kgs)
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Manual Wheelchairs - 0 views

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    Manual wheelchairs are the type that require people to move them, there are three types of manual wheelchairs namely self-propelled, attendant propelled, and wheelbase. Many manual chairs can be folded wheelchairs for storage or movement into a vehicle. A manual wheelchair is one that is propelled by the user. It is usually done by pushing on round bars that surround the wheels. This wheelchair also has handles on the back so it can be pushed by another person. A manual wheelchair is easy to maintain, is lightweight, and is the least expensive to buy. Manual wheelchairs that cater to many different conditions that a user may have. Manual wheelchairs includes a large selection of high quality chairs that are highly competitive in price. It carry many different categories of wheelchairs, depending on condition can find one that best fits lifestyle. Manual Wheelchairs are the type of device that a person must move themselves without the assistance of a battery. It choose from self-propel, which requires the user to propel with the use of their limbs, and companion propelled, which means that must have a person to push. It believe that users will be able to find the best manual wheelchair available for their specific needs. A lightweight manual wheelchair offers a combination of safety and durability with convenient features such as flip-back armrests and swingaway footrests for easier transfers, and height-adjustable rear wheels. It is available in self-propelled and attendant-assisted versions, and can be quickly demounted for easier transportation. It has quick release rear wheels, swing away and detachable armrests, swing in/out footrests, puncture proof tyres, fitted lap belt, folding backrest and lightweight, padded nylon upholstery. Karma Econ 800 Wheelchair The new multi-adjustable ECON 800 is a quality, lightweight aircraft grade aluminium alloy frame wheelchair. The swing-away and detachable footrest's calf length can be adjusted to fit your bod
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Transport Chair - 0 views

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    Lightweight wheelchairs provide convenience and comfort to the user and caregiver alike and are often built using materials like aluminum and titanium alloy, while foldable wheelchairs allow for easy storage and transport. Merge the two styles, and got a great mobility aid that isn't a pain to lug around. Utilizing small wheels and lighter materials, transport wheelchairs can tip the scale at as little as 19 lbs, ideal for those looking for a highly portable option. Transport chairs also tend to be more affordable and offer the benefit of increased mobility without breaking the bank. Transport wheelchairs or companion chairs are companion wheelchairs where the purpose is for a companion to push the user. Most transporters have swing-away leg rests, fixed armrests, and side panels. Instead of the usual large back - small front wheels typical of most wheelchairs, light travel chairs have four small wheels providing much easier maneuverability of the chair. Karma KM 2500 Small Wheel Wheelchair: Karma KM 2500 Small Wheel Wheelchair Specifications: Width 18" Front/Rear Wheels 6" to 14" Seat Width 47cm Seat Depth 40cm Overall Width 66cm Overall Collapsed Width 36cm Armrest Height 21cm Overall Length 90cm Seat Height 47cm Backrest Height 38cm Overall Height 86cm Weight 9.2 k.g. Karma KM 2500 Small Wheel Wheelchair Seat and Back: AEGIS Microbe Shield Approved by the FDA, EPA, EU, etc., bonded anti-microbial barrier upholstery protects from odor, staining and deterioration from bacteria, fungus and other microorganisms. It is a shield for your health. Karma KM 2500 Small Wheel Wheelchair Extended Armrest: By simulating the natural position of arms, the extended armrest design is ergonomic and creates bigger seating space. An Ultra lightweight wheelchair (9.2 kg) with a compact design for either attendant assisted or self propelling users. The use of aircraft-grade aluminium alloy and double cross brace provide this model
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Karman Ergo Lite S-2501 Wheelchair - 0 views

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    Karma Ergo Lite 2501 Wheelchair The extremely lightweight Ergo Lite 2501 Transport Wheelchair weighs only 8.16 kg. and features an ergonomically-designed seat and backrest, making it one of the most comfortable transport chairs on the market. The folding seat and backrest make the S-Ergo ideal for storage or travel, and the built in AEGIS anti-bacterial cushion provides added comfort and support. Despite its light weight, the S-Ergo features a 115 kg. weight capacity along with large, 14" flat-free polyurethane rear tires. Karma Ergo Lite 2501 Wheelchair Features Lightest transporter on the market! Patented S-Style Ergonomic Seat Frame 6061 T-6 Aircraft-grade Aluminum Only 18 lb . (w/ footrests) Built in Silver Aegis Anti-bacterial Cushion Fixed Armrests w/Concaved Armpads Pocket Behind Backrest & Small Carry Pouch on Each Armrest 6" x 1" Polyurethane Front Casters 16" x 17" or 18" x 17" Seat Width S-Style Ergonomic Seat 14" Rear Polyurethane, High Tread, Flat Free Wheels 3-Stage handle brake: allows light to firm grip for lock Folding Backrest/ Folding Seat for Transporting in Vehicle or Travel Fixed Footrests w/ Extra Wide Footplates Frame Color: Pearl Silver Weight Capacity of 100 kg Ergonomic Transporter w/ handle brakes Karma Ergo Lite 2501 Wheelchair Measurements Seat Width 16 inch., 18 inch. Seat Depth 17 inch. Armrest Height 8 inch. Seat Height 19 inch. Back Height 17 inch. Overall Height 36 inch. Overall Open Width 23 inch., 25 inch. Folded Width 12 inch. Overall Length 39 inch. Weight Without Riggings 8 kg. Weight Cap 100 kg. Shipping Dimensions 35" L x 30" H x 12" W
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Karma S-Ergo 105 Manual Wheelchair - 0 views

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    Ergonomic chairs are designed to confirm to a person's physical dimensions, allowing them to sit naturally and comfortably for long periods of time, while reducing the risk of pressure ulcers. Ergonomic system (Intelligent s-shaped ergonomic seating) provides efficient pressure relief by spreading weight over a greater area, at the same time provides stabilization and reduced sliding. With their lightweight frames and seats designed to reduce or prevent pressure points, ergonomic wheelchairs provide a comfortable option for mobility impaired users who have the upper body strength to propel themselves, or a caregiver strong enough to do so. Karma Ergo Lite 2501 Wheelchair: The extremely lightweight Ergo Lite 2501 Transport Wheelchair weighs only 8.16 kg. and features an ergonomically-designed seat and backrest, making it one of the most comfortable transport chairs on the market. The folding seat and backrest make the S-Ergo ideal for storage or travel, and the built in AEGIS anti-bacterial cushion provides added comfort and support. Despite its light weight, the S-Ergo features a 115 kg. weight capacity along with large, 14" flat-free polyurethane rear tires. Karma Ergo Lite 2501 Wheelchair Features: Lightest transporter on the market! Patented S-Style Ergonomic Seat Frame 6061 T-6 Aircraft-grade Aluminum Only 18 lb . (w/ footrests) Built in Silver Aegis Anti-bacterial Cushion Fixed Armrests w/Concaved Armpads Pocket Behind Backrest & Small Carry Pouch on Each Armrest 6" x 1" Polyurethane Front Casters 16" x 17" or 18" x 17" Seat Width S-Style Ergonomic Seat 14" Rear Polyurethane, High Tread, Flat Free Wheels 3-Stage handle brake: allows light to firm grip for lock Folding Backrest/ Folding Seat for Transporting in Vehicle or Travel Fixed Footrests w/ Extra Wide Footplates Frame Color: Pearl Silver Weight Capacity of 100 kg Ergonomic Transporter w/ handle brakes Karma Ergo Lite 2501 Wheelchair Measurements: Seat Width 16 inch., 18
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Improve Safety By Transport wheelchairs - 0 views

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    Walking disabled people are more fortunate nowadays. While in the past they always have felt incapacitated and immobile, nowadays, they are provided with more and better means to roam and move around. With the development and heightened popularity and usage of wheelchairs, such handicapped people are given more advantage and privilege. The emergence of transport wheelchairs have significantly helped improve the way people make use of wheelchairs. Transport wheelchairs are machines or equipment that facilitate for mobility and movement of wheelchair confined people at public places. While it is true that simple wheelchairs can do the trick, transport wheelchairs are specifically designed and manufactured to facilitate better roaming and mobility at malls, restaurants and parks where people usually converge to relax. Transport wheelchairs provide many advantages: Weight: As the name implies, they are easy to transport because they typically weigh around 15 to 20 pounds, which is much less than a manual wheelchair. Storage: They are easier to store than traditional manual and electric wheelchairs. Most are small enough to fit into the trunk of a compact car. Karma Travel Wheelchair KM TV 20.2: Karma Travel Wheelchair KM TV 20.2 - 606 T-6 aircraft-grade aluminum-alloy frame provides incredible strength. Easy-to-fold in three seconds. Karma Travel Wheelchair KM TV 20.2 Features: Type: Travel Wheelchair T-6 aircraft-grade aluminum Secure brake improve safety Padded flip back armrest PU front caster & rear wheel Karma Travel Wheelchair KM TV 20.2 Measurements: Weight: 8.9kg Seat width: 39.5cm Tyre: PU front casters and rear wheels Capacity: 100kg Folded size: (L/W/H): 610mm x 350mm x710mm. Wheelchair provides comfort and mobility in an economical package. It comes standard with padded nylon upholstery and one-piece armrests that offer a cushioned feel with minimal maintenance. Combined with its stylish silver vein frame and matching fr
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Ultra Lightweight Travel Wheelchair With Seat Belt - 0 views

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    Travel Wheelchair is ideal for those looking for an easily portable wheelchair without sacrificing sturdiness or weight capacity. In order to accommodate various heights, models feature adjustable backs and the threaded seat screw inserts reduce stripping from upholstery damage to give the chair a longer life. The wheels feature sealed bearings to keep dirt out, making the wheels virtually maintenance free. The Travel Chair is a lightweight sturdy aluminum framed portable chair. It is easily transportable and comes with a compact carry bag, making it ideal for stowing away in cars, buses, trains, and more. This wheelchair can be used both indoors and outdoors on forgiving terrain, with a convenient step for the attendant to lift the chair over obstacles. This travel chair gives the freedom to go, with the added convenience of folding up to a manageable size. This lightweight Steel Travel Chair with Fixed Full Arms or Detachable Desk Arms has a foldable back, making it convenient and easy to store and transport. The silver vein frame is scratch resistant and it comes standard with a comfortable, durable, and easy to clean, black nylon upholstery seat and back. The caster wheels in front and rear with provide a smooth ride over most surfaces. The padded armrests, rear wheel locks, swing away footrest and seat belt all combine to make this travel chair convenient, durable, easy to transport and safe. Karma Travel Wheelchair KM TV 20.2 Karma Travel Wheelchair KM TV 20.2 - 606 T-6 aircraft-grade aluminum-alloy frame provides incredible strength. Easy-to-fold in three seconds. Karma Travel Wheelchair KM TV 20.2 Features Type: Travel Wheelchair T-6 aircraft-grade aluminum Secure brake improve safety Padded flip back armrest PU front caster & rear wheel Karma Travel Wheelchair KM TV 20.2 Measurements Weight: 8.9kg Seat width: 39.5cm Tyre: PU front casters and rear wheels Capacity: 100kg Folded size: (L/W/H): 610mm x 350mm x710mm. Lightweight wh
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Comfort And Ease Lightweight Wheelchair - 0 views

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    Transport Chair weighs only 14.8 lbs - almost 25% lighter than standard folding transport chairs. The Chair also features breathable nylon upholstery, an attractive colored frame and comfortable, "restaurant-style" arms - so it can pull up to tables and eat comfortably. The chair not only has a fold-down back but is foldable for length-wise for easy transport. The backside of the chair contains a key ring and multiple pockets. Transport chairs make it easier for the loved ones and caregivers to help to get around in comfort and ease. Compared to a standard wheelchair, a transport chair requires a caregiver to push the chair. A transport wheelchair is much lighter than a wheelchair; plus, it is more compact which makes getting around town easier. This chair comes equipped with loop-lock hand brakes that are easy to operate and ideal for locking the rear wheels during transfers. It also has a seatbelt which keeps the passenger securely in place and it is compact when folded making it easy to lift into a car or carry up the stairs. It is equipped with a seat belt, comfortable nylon upholstery, full length permanent armrest, and detachable footrests. It has a 19 inch wide seat that can provide and a weight capacity of 300 pounds. Karma Travel Wheelchair KM TV 20.2: Karma Travel Wheelchair KM TV 20.2 - 606 T-6 aircraft-grade aluminum-alloy frame provides incredible strength. Easy-to-fold in three seconds. Karma Travel Wheelchair KM TV 20.2 Features: Type: Travel Wheelchair T-6 aircraft-grade aluminum Secure brake improve safety Padded flip back armrest PU front caster & rear wheel Karma Travel Wheelchair KM TV 20.2 Measurements: Weight: 8.9kg Seat width: 39.5cm Tyre: PU front casters and rear wheels Capacity: 100kg Folded size: (L/W/H): 610mm x 350mm x710mm. Ultra Lightweight Wheelchair: Its compact design and feather light weight makes it suitable for people on the go. Ultra Lightweight Wheelchair Specifications: Frame Style : Foldabl
wheelchairindia9

Travel Wheelchair For Handicapped With Special Health Care Needs - 0 views

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    A transport wheelchair is designed to only be propelled by another individual and is sometimes referred to as a companion chair or rollabout chair. Transport chairs have four small wheels instead of two small and two large. They come in different widths and weight capacities and are usually the same basic frame as a standard manual wheelchair. Lightweight Transport wheelchair is one of the the lightest transport chairs on the market, weighing in at only 19 lbs! With four great colors to choose from, this can be transported in style. A seat belt and swing-away removable footrests are standard and make it easy to get in and out of this chair. A fold-down back allows for easier storage and transport and padded armrests add additional comfort. Karma KM 2500 Small Wheel Wheelchair: Karma KM 2500 Small Wheel Wheelchair Specifications: Width 18" Front/Rear Wheels 6" to 14" Seat Width 47cm Seat Depth 40cm Overall Width 66cm Overall Collapsed Width 36cm Armrest Height 21cm Overall Length 90cm Seat Height 47cm Backrest Height 38cm Overall Height 86cm Weight 9.2 k.g. Karma KM 2500 Small Wheel Wheelchair Seat and Back: AEGIS Microbe Shield Approved by the FDA, EPA, EU, etc., bonded anti-microbial barrier upholstery protects from odor, staining and deterioration from bacteria, fungus and other microorganisms. It is a shield for your health. Karma KM 2500 Small Wheel Wheelchair Extended Armrest: By simulating the natural position of arms, the extended armrest design is ergonomic and creates bigger seating space. An Ultra lightweight wheelchair (9.2 kg) with a compact design for either attendant assisted or self propelling users. The use of aircraft-grade aluminium alloy and double cross brace provide this model with outstanding strength and durability. Karma Healthcare KM-2500 Premium Wheelchair is amazingly light and compact transit wheelchair which is ideal for outings and travelers. It folds down to take up virtually no sp
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Travel Wheelchair Add Additional Comfort - 0 views

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    Lightweight Transport wheelchair is one of the the lightest transport chairs on the market, weighing in at only 19 lbs! With four great colors to choose from, it can be transported in style. A seat belt and swing-away removable footrests are standard and make it easy to get in and out of this chair. A fold-down back allows for easier storage and transport and padded armrests add additional comfort. It is made out of a lightweight and durable powder coated aluminum frame that is available in either red or blue. It is available in a 19" wide seat with permanent full-length arms and swing-away detachable footrests. The chair also has padded armrests and a seatbelt for safety purposes. Karma Travel Wheelchair KM TV 20.2 Karma Travel Wheelchair KM TV 20.2 - 606 T-6 aircraft-grade aluminum-alloy frame provides incredible strength. Easy-to-fold in three seconds. Karma Travel Wheelchair KM TV 20.2 Features Type: Travel Wheelchair T-6 aircraft-grade aluminum Secure brake improve safety Padded flip back armrest PU front caster & rear wheel Karma Travel Wheelchair KM TV 20.2 Measurements Weight: 8.9kg Seat width: 39.5cm Tyre: PU front casters and rear wheels Capacity: 100kg Folded size: (L/W/H): 610mm x 350mm x710mm. Ultra Lightweight Wheelchair Its compact design and feather light weight makes it suitable for people on the go. Ultra Lightweight Wheelchair Specifications Frame Style : Foldable Frame Material : Aluminium (Light weight) Rear wheel to wheel width in open position (inches) : 20" Handle to Handle : 16" Seat Width (inches): 13" Rear Wheel Size: 7" Front Wheel Size: 5" Seat to floor height (inches): 19" Seat Depth (inches): 13" Back height (inches): 16" Total height (inches): 35" Max User Weight Capacity (kgs): 80 k.g. Net Weight (kgs): 8.5 k.g. Upholstery: Cloth look like, washable Armrest: Flip up, for easy transfer to bed Legrest: Flip up footplate Wheel Quality: Tear resistant polyurethane wheels Rear Wheel Lo
Nathan Goodyear

The river blindness drug Ivermectin and related macrocyclic lactones inhibit WNT-TCF pa... - 0 views

  • WNT signaling
  • early colon cancers commonly display loss of function of the tumor suppressor Adenomatous polyposis coli (APC), a key component of the β-CATENIN destruction complex
  • Other cancers also show an active canonical WNT pathway; these include carcinomas of the lung, stomach, cervix, endometrium, and lung as well as melanomas and gliomas
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  • In normal embryogenesis and homeostasis, the canonical WNT pathway is activated by secreted WNT ligands produced in highly controlled context-dependent manners and in precise amounts. WNT activity is transduced in the cytoplasm, inactivates the APC destruction complex, and results in the translocation of activate β-CATENIN to the nucleus, where it cooperates with DNA-binding TCF/LEF factors to regulate WNT-TCF targets and the ensuing genomic response
  • beyond the loss of activity of the APC destruction complex, for instance throughAPC mutation, phosphorylation of β-CATENIN at C-terminal sites is required for the full activation of WNT-TCF signaling and the ensuing WNT-TCF responses in cancer.
  • The WNT-TCF response blockade that we describe for low doses of Ivermectin suggests an action independent to the deregulation of chloride channels
  • involve the repression of the levels of C-terminally phosphorylated β-CATENIN forms and of CYCLIN D1, a critical target that is an oncogene and positive cell cycle regulator.
  • the Avermectin single-molecule derivative Selamectin, a drug widely used in veterinarian medicine (Nolan & Lok, 2012), is ten times more potent acting in the nanomolar range
  • Ivermectin also diminished the protein levels of CYCLIN D1, a direct TCF target and oncogene, in both HT29 and H358 tumor cells
  • Activated Caspase3 was used as a marker of apoptosis by immunohistochemistry 48 h after drug treatment. Selamectin and Ivermectin induced up to a sevenfold increase in the number of activated Caspase3+ cells in two primary (CC14 and CC36) and two cell line (DLD1 and Ls174T) colon cancer cell types (Fig​(Fig2C).2C). All changes were significative
  • The strong downregulation of the expression of the intestinal stem cell genesASCL2 andLGR5 (van der Flieret al, 2009; Scheperset al, 2012; Zhuet al, 2012b) by Ivermectin and Selamectin (Fig​(Fig2D)2D) raised the possibility that these drugs could affect WNT-TCF-dependent colon cancer stem cell behavior
  • Pre-established H358 tumors responded to Ivermectin showing a ˜ 50% repression of growth
  • Ivermectin hasin vivo efficacy against human colon cancer xenografts sensitive to TCF inhibition with no discernable side effects
  • Ivermectin (Campbellet al, 1983), an off-patent drug approved for human use, and related macrocyclic lactones, have WNT-TCF pathway response blocking and anti-cancer activities
  • these drugs block WNT-TCF pathway responses, likely acting at the level of β-CATENIN/TCF function, affecting β-CATENIN phosphorylation status.
  • anti-WNT-TCF activities of Ivermectin and Selamectin
  • Ivermectin has a well-known anti-parasitic activity mediated via the deregulation of chloride channels, leading to paralysis and death (Hibbs & Gouaux, 2011; Lynagh & Lynch, 2012). The same mode of action has been suggested to underlie the toxicity of Ivermectin for liquid tumor cells and the potentiation or sensitization effect of Avermectin B1 on classical chemotherapeutics
  • the specificity of the blockade of WNT-TCF responses we document, at low micromolar doses for Ivermectin and low nanomolar doses for Selamectin, indicate that the blockade of WNT-TCF responses and chloride channel deregulation are distinct modes of action
  • What is key then is to find a dose and a context where the use of Ivermectin has beneficial effects in patients, paralleling our results with xenografts in mice.
  • Cell toxicity appears at doses greater (> 10 μM for 12 h or longer or > 5 μM for 48 h or longer for Ivermectin) than those required to block TCF responses and induce apoptosis.
  • Our data point to a repression of WNT-β-CATENIN/TCF transcriptional responses by Ivermectin, Selamectin and related macrocylic lactones.
  • (i) The ability of Avermectin B1 to inhibit the activation of WNT-TCF reporter activity by N-terminal mutant (APC-insensitive) β-CATENIN as detected in our screen
  • (ii) The ability of Avermectin B1, Ivermectin, Doramectin, Moxidectin and Selamectin to parallel the modulation of WNT-TCF targets by dnTCF
  • (iii) The finding that the specific WNT-TCF response blockade by low doses of Ivermectin and Selamectin is reversed by constitutively active TCF
  • (iv) The repression of key C-terminal phospho-isoforms of β-CATENIN resulting in the repression of the TCF target and positive cell cycle regulator CYCLIN D1 by Ivermectin and Selamectin
  • (v) The specific inhibition ofin-vivo-TCF-dependent, but notin-vivo-TCF-independent cancer cells by Ivermectin in xenografts.
  • These results together with the reduction of the expression of the colon cancer stem cell markersASCL2 andLGR5 (e.g., Hirschet al, 2013; Ziskinet al, 2013) raise the possibility of an inhibitory effect of Ivermectin, Selamectin and related macrocyclic lactones on TCF-dependent cancer stem cells.
  • the capacity of cancer cells to form 3D spheroids in culture, as well as the growth of these, is also WNT-TCF-dependent (Kanwaret al, 2010) and they were also affected by Ivermectin treatment
  • If Ivermectin is specific, it should only block TCF-dependent tumor growth. Indeed, the sensitivity and insensitivity of DLD1 and CC14 xenografts to Ivermectin treatment, respectively, together with the desensitization to Ivermectin actionin vivo by constitutively active TCF provide evidence of the specificity of this drug to block an activated WNT-TCF pathway in human cancer.
  • Ivermectin has a good safety profile since onlyin-vivo-dnTCF-sensitive cancer xenografts are responsive to Ivermectin treatment, and we have not detected side effects in Ivermectin-treated mice at the doses used
  • previous work has shown that side effects from systemic treatments with clinically relevant doses in humans are rare (Yang, 2012), that birth defects were not observed after exposure of pregnant mothers (Pacquéet al, 1990) and that this drug does not cross the blood–brain barrier (Kokozet al, 1999). Similarly, only dogs with mutantABCB1 (MDR1) alleles leading to a broken blood–brain barrier show Ivermectin neurotoxicity (Mealeyet al, 2001; Orzechowskiet al, 2012)
  • Indications may include treatment for incurable β-CATENIN/TCF-dependent advanced and metastatic human tumors of the lung, colon, endometrium, and other organs.
  • Ivermectin, Selamectin, or related macrocyclic lactones could also serve as topical agents for WNT-TCF-dependent skin lesions and tumors such as basal cell carcinomas
  • they might also be useful as routine prophylactic agents, for instance against nascent TCF-dependent intestinal tumors in patients with familial polyposis and against nascent sporadic colon tumors in the general aging population
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    Ivermectin, a common anti-parasitic, found to inhibit WTF-TCF pathway and decrease c-terminal phosophorylaiton of Beta-CATENIN all resulting in increased aptosis and inhibition of cancer growth in colon cancer cell lines and lung cancer cell lines.
Nathan Goodyear

Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde... - 0 views

  • Hydroxyl radicals cause oxidative damage to cells because they unspecifically attack biomolecules [22] located less than a few nanometres from its site of generation and are involved in cellular disorders such as neurodegeneration [23, 24], cardiovascular disease [25], and cancer [26, 27].
  • It is generally assumed that in biological systems is formed through redox cycling by Fenton reaction, where free iron (Fe2+) reacts with hydrogen peroxide (H2O2) and the Haber-Weiss reaction that results in the production of Fe2+ when superoxide reacts with ferric iron (Fe3+)
  • other transition-metal including Cu, Ni, Co, and V can be responsible for formation in living cells
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  • The hydroperoxyl radical () plays an important role in the chemistry of lipid peroxidation
  • The is a much stronger oxidant than superoxide anion-radical
  • Lipid peroxidation can be described generally as a process under which oxidants such as free radicals or nonradical species attack lipids containing carbon-carbon double bond(s), especially polyunsaturated fatty acids (PUFAs) that involve hydrogen abstraction from a carbon, with oxygen insertion resulting in lipid peroxyl radicals and hydroperoxides as described previously
  • under medium or high lipid peroxidation rates (toxic conditions) the extent of oxidative damage overwhelms repair capacity, and the cells induce apoptosis or necrosis programmed cell death
  • The overall process of lipid peroxidation consists of three steps: initiation, propagation, and termination
  • Once lipid peroxidation is initiated, a propagation of chain reactions will take place until termination products are produced.
  • The main primary products of lipid peroxidation are lipid hydroperoxides (LOOH)
  • Among the many different aldehydes which can be formed as secondary products during lipid peroxidation, malondialdehyde (MDA), propanal, hexanal, and 4-hydroxynonenal (4-HNE) have been extensively studied
  • MDA has been widely used for many years as a convenient biomarker for lipid peroxidation of omega-3 and omega-6 fatty acids because of its facile reaction with thiobarbituric acid (TBA)
  • MDA is one of the most popular and reliable markers that determine oxidative stress in clinical situations [53], and due to MDA’s high reactivity and toxicity underlying the fact that this molecule is very relevant to biomedical research community
  • 4-HNE is considered as “second toxic messengers of free radicals,” and also as “one of the most physiologically active lipid peroxides,” “one of major generators of oxidative stress,” “a chemotactic aldehydic end-product of lipid peroxidation,” and a “major lipid peroxidation product”
  • MDA is an end-product generated by decomposition of arachidonic acid and larger PUFAs
  • Identifying in vivo MDA production and its role in biology is important as indicated by the extensive literature on the compound (over 15 800 articles in the PubMed database using the keyword “malondialdehyde lipid peroxidation” in December 2013)
  • MDA reactivity is pH-dependent
  • When pH decreases MDA exists as beta-hydroxyacrolein and its reactivity increases
  • MAA adducts are shown to be highly immunogenic [177–181]. MDA adducts are biologically important because they can participate in secondary deleterious reactions (e.g., crosslinking) by promoting intramolecular or intermolecular protein/DNA crosslinking that may induce profound alteration in the biochemical properties of biomolecules and accumulate during aging and in chronic diseases
  • MDA is an important contributor to DNA damage and mutation
  • This MDA-induced DNA alteration may contribute significantly to cancer and other genetic diseases.
  • Dietary intake of certain antioxidants such as vitamins was associated with reduced levels of markers of DNA oxidation (M1dG and 8-oxodG) measured in peripheral white blood cells of healthy subjects, which could contribute to the protective role of vitamins on cancer risk
  • 4-HNE is an extraordinarily reactive compound
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    Great review of lipid peroxidation
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