Sunday 29 March 2015

The Best of smoothie's recipes: Lemon cooler

Weight Loss the Easy Ways 
Andrea Albright Featured on Health and Fitness Jan. 2015
will Personally Coach You How to Get There The Easy Way

Posted By Kyle J. Norton
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.

The (safe, nutritious, easy to prepare snacks for any occasion) ultimate allergy-free snack cookbook by Judi and Shari Zucker, Square one publishers. Over 100 kid -friendly recipes for the allergic child.

This drink is smooth, creamy and super frosty!

There is nothing like a homemade lemonade. It is the perfect drink to serve with chips and dips.
Yield 4 servings, about 8 ounces each.

2/3 cup fresh lemon juice (3 - 4 large lemons)
1/3 cup date sugar  or to taste
3 cups cold waters

1. Place a lemon juice and date sugar in a small bowl and stir until sugar is dissolved.
2. Transfer the mixture to a pitcher, add the cold water and stir well.
3. Serve as is or over ice.

Change it up.....For a  add of spark of flavor  and to turn the lemonade a fun pink color, add 1/4 cup cranberry or raspberry juice.
For a carbonated version, use sparkling water.
For Over 1000 recipes http://kylejnorton.blogspot.ca/p/recipes.html

Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer

Saturday 28 March 2015

The Holistic prevention, management and treatment of Polycystic Ovarian Syndrome: The Causes(Revised edition with Citations)

Weight Loss the Easy Ways
Andrea Albright Featured on Health and Fitness Jan. 2015
will Personally Coach You How to Get There The Easy Way

If You Are Looking For a SoulMate
Celebrity Patti Stanger Will Coach You To Get Him/Her
and Keep Him/Her for Good,The Simple Way

By Kyle J. Norton Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.




                           Polycystic Ovarian Syndrome


Polycystic Ovarian Syndrome is defined as endocrinologic diseases among reproductive-age women caused by undeveloped follicles clumping on the ovaries that interferes with the function of the normal ovaries associated with a high risk for metabolic disorder(1) as resulting of enlarged ovaries(2), leading to hormone imbalance(excessive androgen and anti-müllerian hormone (AMH) )(1)(3)(4)(5), induced Hirsutism(6)(7), reproductive disorder(10(12)), risks of type 2 diabetes(9)(10)(11), metabolic syndrome(10)(12) and early cardiovasular disease(8)(13), acne(10)(14), endometrial cance(18)(19),weight gain and obesity(15)(16)(17). The syndrome effects over 5% of women population or 1 in 20 women.
Unfortunately, according to studies, women with PCOs after the reproductive age, are associated to  continuously increase risk of type II diabetes, with no increasing altered glucose tolerance(20), CVD and hypertension(21).


                                           The Causes

The causes of polycystic ovarian syndrome are still unknown(69)(70), but there are some suggestions
1. Genetic predisposition
A genetic predisposition is defined as a genetic mutation of some women who were born predisposed to certain health problems(75). In this case, it is polycystic ovarian syndrome(70)(71)(72)(73)(74) .

2. Insulin resistance(82)
Insulin resistance is defined as abnormal levels of insulin in the blood of a person found to be associated to women with PCOs(83). It may be caused by certain health problems such as diabetes(76)(77), abnormal function of pancreas(78)(79) or caused low numbers of the insulin sensitivity of cells(79)(80), which impair the process of glucose in energy conversion(81), induced high blood glucose levels in the body, cause of increasing the risks of ovarian cysts development(83).

3. Obesity(84)
Obesity is defined as a person whose BMI index is over 24. As we known, obesity women in most cases are associated to clinical feature of insulin resistance(76). According to Università Cattolica del Sacro Cuore, low 25(OH)D levels(86) accompanied with the degree of adiposity may induce the causation of PCOs(85).

4. Hyperandrogenism
Hyperandrogenism is a medical condition characterized by excessive production and/or secretion of androgens leading to male pattern hair growth, probably due to mutation in the polymorphism rs12720071 in women(88). According to  Erciyes University, there is a relation between IR(Insulin resistance) and androgenetic alopecia (AGA)(87), a male pattern baldness.
Hirsutism develops when follicles in androgen sensitive areas start to form thick, pigmented hair as opposed to thin, short, non-pigmented hair normally seen in those areas in women with PCOs(89). Evaluating terminal hair growth on the chin or lower abdomen may be a reliable source for predicting hirsutism, according to Ahvaz Jundishapur University of Medical Sciences(90).

5. Environmental chemicals
Environment chemicals endocrine disruptors(91)(92), such as such as xanoestrogen, and lifestyle(91)(92) can causes over production of certain hormone and reduction of others, leading to abnormal function of the reproductive organs including the development of follicles and increasing the risk of PCOs(93).

6. Food adulteration
Food adulteration, including mixing, substituting, concealing the quality of food by mislabeling, putting up decomposed or expired food, and adding toxic substances(94) can lead to hormone imbalance(98) and distort the natural process of women reproductive system(97) and in same cases, result in death(95)(96).

7. Chronic inflammation
Prolonged inflammation, known as chronic inflammation, leads to a progressive shift in the type of cells which are present at the site of inflammation and is characterized by simultaneous destruction and healing of the tissue from the inflammatory process(99)(100)(101).

8. Disorders of cortisol metabolism
Cortisol is usually referred to as the stress hormone, presented in high levels in patients with schizophrenia and bipolar disorder(104) as it is secreted in large volume for our body to response to stress and anxiety(103). Disorders of cortisol metabolism is defined as a condition of which cortisol hormone has lost its function in restoring glucose homeostasis(105) in balancing insulin and glucagon in the blood stream(107). According to University College London Hospitals, altered cortisol metabolism does not seem to be the primary cause of PCOS(102).



Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months   


References
(1) Adiposity and metabolic dysfunction in polycystic ovary syndrome by Sam S.(PubMed)
(2) A "kiss" before conception: triggering ovulation with kisspeptin-54 may improve IVF by Young SL.(PubMed)
(3.) Androgen hyperfunction and excessive heterosexual hair growth in women, with special attention to the polycystic ovarian syndrome by Lunde O1.(PubMed)
(4) Expression of anti-Müllerian hormone in letrozole rat model of polycystic ovary syndrome by Du DF1, Li XL, Fang F, Du MR.(PubMed)
(5) [Serum levels of anti-muller hormone in women with polycystic ovary syndrome and healthy women of reproductive age].[Article in Bulgarian] by Parahuleva N, Pehlivanov B, Orbecova M, Deneva T, Uchikova E.(PubMed)
(6) [Current opinions on the etiology and pathophysiology of hirsutism].[Article in Polish] by Krysiak R1, Kedzia A, Okopień B.(PubMed)
(7) The clinical evaluation of hirsutism by Somani N1, Harrison S, Bergfeld WF.(PubMed)
(8) Polycystic ovary syndrome and insulin: our understanding in the past, present and future by Mayer SB1, Evans WS, Nestler JE.(PubMed)
(9) Association of mean platelet volume with androgens and insulin resistance in nonobese patients with polycystic ovary syndrome by Dogan BA1, Arduc A2, Tuna MM1, Karakılıc E1, Dagdelen I1, Tutuncu Y1, Berker D1, Guler S1.(PubMed)
(10) Approach to the patient: contraception in women with polycystic ovary syndrome by Yildiz BO1.(PubMed)
(11) Polycystic ovarian syndrome (PCOS): a significant contributor to the overall burden of type 2 diabetes in women by Talbott EO1, Zborowski JV, Rager JR, Kip KE, Xu X, Orchard TJ.(PubMed)
(12) Prevalence of vitamin D deficiency in Slovak women with polycystic ovary syndrome and its relation to metabolic and reproductive abnormalities by Figurová J1, Dravecká I, Javorský M, Petríková J, Lazúrová I.(PubMed)
(13) Role of Insulin Sensitizers on Cardiovascular Risk Factors in Polycystic Ovarian Syndrome: A Meta-Analysis by Thethi TK1, Katalenich B2, Nagireddy P3, Chabbra P4, Kuhadiya N5, Fonseca V1.(PubMed)
(14) Acne in hirsute women by Lumezi BG1, Pupovci HL1, Berisha VL1, Goçi AU2, Gerqari A3.(PubMed)
(15) Obesity and polycystic ovary syndrome by Naderpoor N1, Shorakae S, Joham A, Boyle J, De Courten B, Teede HJ.(PubMed)
(16) Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan by Teede H1, Deeks A, Moran L.(PubMed)
(17) Metabolic Evidence of Diminished Lipid Oxidation in Women With Polycystic Ovary Syndrome. by Whigham LD1, Butz DE2, Dashti H3, Tonelli M3, Johnson LK1, Cook ME2, Porter WP4, Eghbalnia HR5, Markley JL6, Lindheim SR7, Schoeller DA8, Abbott DH9, Assadi-Porter FM10.(PubMed)
(18) Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis by Barry JA1, Azizia MM1, Hardiman PJ2.(PubMed)
(19) Risk of cancer among women with polycystic ovary syndrome: a Danish cohort study by Gottschau M1, Kjaer SK2, Jensen A1, Munk C1, Mellemkjaer L3.(PubMed)
(20) Polycystic ovary syndrome: metabolic consequences and long-term management by Carmina E1.(PubMed)
(21) Arterial stiffness is increased in asymptomatic nondiabetic postmenopausal women with a polycystic ovary syndrome phenotype by Armeni E1, Stamatelopoulos K, Rizos D, Georgiopoulos G, Kazani M, Kazani A, Kolyviras A, Stellos K, Panoulis K, Alexandrou A, Creatsa M, Papamichael C, Lambrinoudaki I.(PubMed)


(65) [Association between levels of serum leptin and insulin resistance in patients with polycystic ovary syndrome].[Article in Chinese]by Cheng X1, Guo J2, Xie J3.(PubMed)
(66) [Clinical study on treating insulin resistance and promoting ovulation in polycystic ovary syndrome].[Article in Chinese]by Liu ZA1, Xue YM, Chen LX, Cai Q, Chen H, Zhang J, Cui QH, Ge J, Yuan T.(PubMed)
(67) Randomized clinical trial evaluating metformin versus oral contraceptive pills in the treatment of adolescents with polycystic ovarian syndrome by Al-Zubeidi H, Klein KO.(PubMed)
(68) Randomized controlled trial evaluating response to metformin versus standard therapy in the treatment of adolescents with polycystic ovary syndrome by Allen HF1, Mazzoni C, Heptulla RA, Murray MA, Miller N, Koenigs L, Reiter EO.(PubMed)
(69) [Polycystic ovary syndrome: physiopathology review].[Article in Spanish]by Fux Otta C, Fiol de Cuneo M, Szafryk de Mereshian P.(PubMed)
(70) Trp28Arg/Ile35Thr LHB gene variants are associated with elevated testosterone levels in women with polycystic ovary syndrome by Batista MC1, Duarte Ede F2, Borba MD3, Zingler E4, Mangussi-Gomes J3, dos Santos BT5, de Moraes OL5, Hayashida SA6, Baracat EC6, da Rocha Neves Fde A5, Maciel GA6, Bachega TA7, Barra GB8, Lofrano-Porto A9.(PubMed)
(71) Polycystic ovary syndrome woman with heterozygous androgen receptor gene mutation who gave birth to a child with androgen insensitivity syndrome by Nam H1, Kim CH2, Cha MY1, Kim JM3, Kang BM1, Yoo HW3.(PubMed)
(72) The role of androgen receptor activity mediated by the CAG repeat polymorphism in the pathogenesis of PCOS by Baculescu N1.(PubMed)
(73) Study on the zona pellucida 4 (ZP4) gene sequence and its expression in the ovaries of patients with polycystic ovary syndrome by Meczekalski B1, Nawrot R, Nowak W, Czyzyk A, Kedzia H, Gozdzicka-Jozefiak A.(PubMed)
(74) Association study of polymorphism of FXIIIVal34Leu gene and polycystic ovary syndrome by Wang X1, Yang Y1, Huang Y2, Wang Q3.(PubMed)
(75) Epigenetics and migraine; complex mitochondrial interactions contributing to disease susceptibility by Roos-Araujo D1, Stuart S1, Lea RA1, Haupt LM1, Griffiths LR2.(PubMed)
(76) Mechanisms linking obesity to insulin resistance and type 2 diabetes by Kahn SE1, Hull RL, Utzschneider KM.(PubMed)
(77) The effect of past antibiotic exposure on diabetes risk by Boursi B1, Mamtani R2, Haynes K3, Yang YX4.(PubMed)
(78) Portal versus systemic venous drainage of the pancreatic graft: the effect on glucose metabolism in pancreas and kidney transplant recipients by Havrdova T1, Boucek P2, Jedinakova T2, Lipar K3, Kocik M3, Skibova J4, Saudek F2.(PubMed)
(79) The mechanisms linking adiposopathy to type 2 diabetes by Yang J1, Kang J, Guan Y.(PubMed)
(80) Caffeic acid, naringenin and quercetin enhance glucose-stimulated insulin secretion and glucose sensitivity in INS-1E cells by Bhattacharya S1, Oksbjerg N, Young JF, Jeppesen PB.(PubMed)
(81) Insulin resistance and adipogenesis: role of transcription and secreted factors by Penkov DN1, Egorov AD, Mozgovaya MN, Tkachuk VA.(PubMed)
(82) Insulin resistance in PCOS by Diamanti-Kandarakis E1(PubMed)
(83) Mouse models to study polycystic ovary syndrome: a possible link between metabolism and ovarian function? by van Houten EL1, Visser JA2.(PubMed)
(84)Epidemiologic investigation of polycystic ovarian syndrome (PCOS) in Han ethnic women of reproductive age in Liaoning Province, China by Jiao J, Fang Y, Wang T, Wang Z, Zhou M, Wang X.(PubMed)
(85) Low levels of 25(OH)D and insulin-resistance: 2 unrelated features or a cause-effect in PCOS?by Muscogiuri G1, Policola C, Prioletta A, Sorice G, Mezza T, Lassandro A, Della Casa S, Pontecorvi A, Giaccari A.(PubMed)
(86) Association of hypovitaminosis D with metabolic disturbances in polycystic ovary syndrome by Wehr E1, Pilz S, Schweighofer N, Giuliani A, Kopera D, Pieber TR, Obermayer-Pietsch B.(PubMed)
(87) The association of androgenetic alopecia and insulin resistance is independent of hyperandrogenemia: A case-control study by Kartal D1, Borlu M, Çınar SL, Ferahbaş A, Ulaş Y, Ünlühızarcı K, Ukşal Ü, Keleştimur F.(PubMed)
(88) GG genotype Selected CNR1 polymorphisms and hyperandrogenemia as well as fat mass and fat distribution in women with polycystic ovary syndrome by Jędrzejuk D1, Laczmański L, Kuliczkowska J, Lenarcik A, Trzmiel-Bira A, Hirnle L, Dorobisz U, Milewicz A, Lwow F, Urbanovych A, Słoka N.(PubMed)
(89) Women self-perception of excess hair growth, as a predictor of clinical hirsutism: a population-based study by Kazemi H1, Ramezani Tehrani F, Minooee S, Khalili D, Azizi F.(PubMed)
(90) Evaluation of only the chin or lower abdomen for predicting hirsutism by Rashidi H1, Parizi ZT, Mohammadi M.(PubMed)
(91) The Pancreas Is Altered by In Utero Androgen Exposure: Implications for Clinical Conditions Such as Polycystic Ovary Syndrome (PCOS) by Mick Rae, Cathal Grace, Kirsten Hogg, Lisa Marie Wilson, Sophie L. McHaffie,2 Seshadri Ramaswamy, Janis MacCallum, Fiona Connolly, Alan S. McNeilly,and Colin Duncan (PubMed)
(92) Prenatal androgen exposure leads to alterations in gene and protein expression in the ovine fetal ovary by Hogg K1, McNeilly AS, Duncan WC.(PubMed)
(93) Endocrine-Disrupting Chemicals: Some Actions of POPs on Female Reproduction by Ewa L. Gregoraszczuk* and Anna Ptak(PubMed)
(94) Food Adulteration and Consumer Awareness in Dhaka City, 1995-2011 By Sharifa Nasreencorresponding author1 and Tahmeed Ahmed(PubMed)
(95) FAO/WHO. Assuring food safety and quality: guidelines for strengthening national food control systems. Rome: Food and Agriculture Organization; 2003. p. 28. (FAO food and nutrition paper no. 76).
(96) Park K. Park's textbook of preventive and social medicine. 18th ed. Jabalpur: Banarsidas Bhanot; 2005. p. 481.
(97) Menstrual effects among women exposed to polychlorinated biphenyls and dibenzofurans by Yang CY1, Huang TS, Lin KC, Kuo P, Tsai PC, Guo YL.(PubMed)
(98) Endocrine modulators in the food chain and environment by Nilsson R1.(PubMed)
(99) Adipose tissue dysfunction, adipokines and low-grade chronic inflammation in PCOS by Spritzer PM1, Lecke SB2, Satler F3, Morsch DM4.(PubMed)
(100) Adipose tissue dysfunction in polycystic ovary syndrome by Villa J1, Pratley RE.(PubMed)
(101) Adipose tissue, metabolic syndrome and polycystic ovary syndrome: from pathophysiology to treatment by Garruti G1, Depalo R, Vita MG, Lorusso F, Giampetruzzi F, Damato AB, Giorgino F.(PubMed)
(102) Altered cortisol metabolism in polycystic ovary syndrome: insulin enhances 5alpha-reduction but not the elevated adrenal steroid production rates by Tsilchorozidou T1, Honour JW, Conway GS.(PubMed)
(103) Increased testosterone levels and cortisol awakening responses in patients with borderline personality disorder: Gender and trait aggressiveness matter by Rausch J1, Gäbel A1, Nagy K1, Kleindienst N2, Herpertz SC1, Bertsch K3.(PubMed|)
(104) Increased systemic cortisol metabolism in patients with schizophrenia and bipolar disorder: a mechanism for increased stress vulnerability? by Steen NE1, Methlie P, Lorentzen S, Hope S, Barrett EA, Larsson S, Mork E, Almås B, Løvås K, Agartz I, Melle I, Berg JP, Andreassen OA.(PubMed)
(105) Elevated maternal cortisol leads to relative maternal hyperglycemia and increased stillbirth in ovine pregnancy by Keller-Wood M1, Feng X2, Wood CE3, Richards E2, Anthony RV4, Dahl GE5, Tao S5.(PubMed)
(106) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man by Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC.(PubMed)
(107) Glucose Homeostasis and Starvation(Glucose Homeostasis)



The Best of smoothie's recipes: Banana frosty freeze

Weight Loss the Easy Ways 
Andrea Albright Featured on Health and Fitness Jan. 2015
will Personally Coach You How to Get There The Easy Way

Posted By Kyle J. Norton
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.

The (safe, nutritious, easy to prepare snacks for any occasion) ultimate allergy-free snack cookbook by Judi and Shari Zucker, Square one publishers. Over 100 kid -friendly recipes for the allergic child.

This drink is smooth, creamy and super frosty!

Yield 3 servings, about 8 ounces each

2 medium-size ripe  banana cup into small chunks
1 1/2 cup frozen peach slices
1/2 frozen orange juice concentrate
1/2 cup rice milk
1 teaspoon honey
4-6 ice cubes

1. Place all ingredients in a blender
2. Blend on high speed or until mixture is smoothed for about 1 minute or until mixture is smooth and the ice well crushed.
3. Serve immediately.

For Over 1000 recipes http://kylejnorton.blogspot.ca/p/recipes.html

Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer

Friday 27 March 2015

The Holistic prevention, management and treatment of Polycystic Ovarian Syndrome: The Diagnosis(Revised edition with Citations)

Weight Loss the Easy Ways
Andrea Albright Featured on Health and Fitness Jan. 2015
will Personally Coach You How to Get There The Easy Way

If You Are Looking For a SoulMate
Celebrity Patti Stanger Will Coach You To Get Him/Her
and Keep Him/Her for Good,The Simple Way

By Kyle J. Norton Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.




                      Polycystic Ovarian Syndrome


Polycystic Ovarian Syndrome is defined as endocrinologic diseases among reproductive-age women caused by undeveloped follicles clumping on the ovaries that interferes with the function of the normal ovaries associated with a high risk for metabolic disorder(1) as resulting of enlarged ovaries(2), leading to hormone imbalance(excessive androgen and anti-müllerian hormone (AMH) )(1)(3)(4)(5), induced Hirsutism(6)(7), reproductive disorder(10(12)), risks of type 2 diabetes(9)(10)(11), metabolic syndrome(10)(12) and early cardiovasular disease(8)(13), acne(10)(14), endometrial cance(18)(19),weight gain and obesity(15)(16)(17). The syndrome effects over 5% of women population or 1 in 20 women.
Unfortunately, according to studies, women with PCOs after the reproductive age, are associated to  continuously increase risk of type II diabetes, with no increasing altered glucose tolerance(20), CVD and hypertension(21).


                                           The Diagnosis


If you have experienced some of above symptoms, it is for your benefit to visit your doctor or gynecologist immediately. PCOs is easy to identify through your
1. Medical history, including question of your symptoms, such as menstrual irregularity, weight change, skin and sleep patterns, as well as all symptoms may contribute to the susceptible PCOs.
a. History of pregnancy including difficulty to conceive, miscarriage, poor neonatal and maternal pregnancy outcomes(46)(47) ...
b. Medication may influence the development of PCOs

2. Physical exam
The aim of the physicam exam is to check for PCOs symptoms, such as pelvic exam for enlarge and abnormal ovaries, male pattern hair growth, acne, weight gain, body mass index (BMI)(48)(49) etc., and risk of diseases caused by PCOs, such as hypertension, thyroid abnormality(50)(51).
(Please check citations in the topics of symptoms and risk factors)

3. Pelvic ultrasound
The aim of the test is to check for enlarge ovaries(2) and cysts(52). Unfortunately, many women with PCOs do not show these abnormalities.

4. Blood test
The blood test includes testing of
a. Dehydroepiandrosterone(DHEA), is a test for excess adrenal precursor androgen (APA) production(53)(54) found in approximately 20-30% of women with PCOS(53).

b Abnormal testosterone(55) levels may interference with the follicle incubation medium(55)(56).

c. Sex hormone-binding globulin (SHBG)(57) is a surrogate marker of insulin resistance
Lower levels of SHBG are found in women with PCOs(58)

d. Follicle-stimulating hormone (FSH)/LH ratio(LH(58) and FSH ratio(58)(59)). Dr. Li Y and the research team at Second Affiliated Hospital of Sun Yat-sen University, said "PCOS patients with higher LH/FSH ratio are primarily caused by hypothalamic-pituitary dysfunction, while the PCOS patients with normal LH/FSH ratio are mainly caused by metabolic disorders"(60).

e. Thyroid-stimulating hormone (TSH)
The aim of the test is to check for levels of TSH (> or =2.5 mIU/l) as the hormone has shown to significantly alter endocrine and metabolic changes(64)
Thyroid dysfunctionis found to be associated to independent risks of ovarian failure and pregnancy related complications in women with Polycystic ovarian syndrome (PCOS)(61). It is said that both PCOS patients combined with SCH have higher risk of cardiovascular risk factors(62)and subclinical hypothyroidism (SCH) is more common in women with PCOs(63).

f. IGTT level (fasting insulin)(65)(66) and several other androgens(67)(68) are used to evaluate adrenal function. If there are abnormal secretion of certain hormones, you may be at a high risk of having PCOs.
Low birth weight may contribute the causation of hyperandrogenism and insulin resistance in adolescents with PCOS, according to the joint study in Italy(64).

Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months   


References
(1) Adiposity and metabolic dysfunction in polycystic ovary syndrome by Sam S.(PubMed)
(2) A "kiss" before conception: triggering ovulation with kisspeptin-54 may improve IVF by Young SL.(PubMed)
(3.) Androgen hyperfunction and excessive heterosexual hair growth in women, with special attention to the polycystic ovarian syndrome by Lunde O1.(PubMed)
(4) Expression of anti-Müllerian hormone in letrozole rat model of polycystic ovary syndrome by Du DF1, Li XL, Fang F, Du MR.(PubMed)
(5) [Serum levels of anti-muller hormone in women with polycystic ovary syndrome and healthy women of reproductive age].[Article in Bulgarian] by Parahuleva N, Pehlivanov B, Orbecova M, Deneva T, Uchikova E.(PubMed)
(6) [Current opinions on the etiology and pathophysiology of hirsutism].[Article in Polish] by Krysiak R1, Kedzia A, Okopień B.(PubMed)
(7) The clinical evaluation of hirsutism by Somani N1, Harrison S, Bergfeld WF.(PubMed)
(8) Polycystic ovary syndrome and insulin: our understanding in the past, present and future by Mayer SB1, Evans WS, Nestler JE.(PubMed)
(9) Association of mean platelet volume with androgens and insulin resistance in nonobese patients with polycystic ovary syndrome by Dogan BA1, Arduc A2, Tuna MM1, Karakılıc E1, Dagdelen I1, Tutuncu Y1, Berker D1, Guler S1.(PubMed)
(10) Approach to the patient: contraception in women with polycystic ovary syndrome by Yildiz BO1.(PubMed)
(11) Polycystic ovarian syndrome (PCOS): a significant contributor to the overall burden of type 2 diabetes in women by Talbott EO1, Zborowski JV, Rager JR, Kip KE, Xu X, Orchard TJ.(PubMed)
(12) Prevalence of vitamin D deficiency in Slovak women with polycystic ovary syndrome and its relation to metabolic and reproductive abnormalities by Figurová J1, Dravecká I, Javorský M, Petríková J, Lazúrová I.(PubMed)
(13) Role of Insulin Sensitizers on Cardiovascular Risk Factors in Polycystic Ovarian Syndrome: A Meta-Analysis by Thethi TK1, Katalenich B2, Nagireddy P3, Chabbra P4, Kuhadiya N5, Fonseca V1.(PubMed)
(14) Acne in hirsute women by Lumezi BG1, Pupovci HL1, Berisha VL1, Goçi AU2, Gerqari A3.(PubMed)
(15) Obesity and polycystic ovary syndrome by Naderpoor N1, Shorakae S, Joham A, Boyle J, De Courten B, Teede HJ.(PubMed)
(16) Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan by Teede H1, Deeks A, Moran L.(PubMed)
(17) Metabolic Evidence of Diminished Lipid Oxidation in Women With Polycystic Ovary Syndrome. by Whigham LD1, Butz DE2, Dashti H3, Tonelli M3, Johnson LK1, Cook ME2, Porter WP4, Eghbalnia HR5, Markley JL6, Lindheim SR7, Schoeller DA8, Abbott DH9, Assadi-Porter FM10.(PubMed)
(18) Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis by Barry JA1, Azizia MM1, Hardiman PJ2.(PubMed)
(19) Risk of cancer among women with polycystic ovary syndrome: a Danish cohort study by Gottschau M1, Kjaer SK2, Jensen A1, Munk C1, Mellemkjaer L3.(PubMed)
(20) Polycystic ovary syndrome: metabolic consequences and long-term management by Carmina E1.(PubMed)
(21) Arterial stiffness is increased in asymptomatic nondiabetic postmenopausal women with a polycystic ovary syndrome phenotype by Armeni E1, Stamatelopoulos K, Rizos D, Georgiopoulos G, Kazani M, Kazani A, Kolyviras A, Stellos K, Panoulis K, Alexandrou A, Creatsa M, Papamichael C, Lambrinoudaki I.(PubMed)
(46) Female Obesity and Infertility by Talmor A1, Dunphy B2.(PubMed)
(47) [Reproductive problems in women with PCOS, the impact of PAL-1 CARRIERS OF 4G PAI -1 polymorphism and BMI].[Article in Bulgarian] by Komsa-Penkova R, Golemanov G, Georgieva G, Slavov N, Popovski K, Ivanov P, Kovacheva K, Atanasova M, Blajev A.(PubMed)
(48) Endothelial function in young women with polycystic ovary syndrome (PCOS): Implications of body mass index (BMI) and insulin resistance by El-Kannishy G1, Kamal S2, Mousa A2, Saleh O2, Badrawy AE2, Farahaty RE2, Shokeir T2.(PubMed)
(49) Body Mass Index and Gonadotropin Hormones (LH & FSH) Associate With Clinical Symptoms Among Women With Polycystic Ovary Syndrome by Esmaeilzadeh S, Andarieh MG1, Ghadimi R, Delavar MA.(PubMed)
(50) Thyroid disorders in polycystic ovarian syndrome subjects: A tertiary hospital based cross-sectional study from Eastern India by Sinha U1, Sinharay K, Saha S, Longkumer TA, Baul SN, Pal SK.(PubMed)
(51) The evaluation and management of hirsutism by Azziz R1.(PubMed)
(52) Pcos.[No authors listed](PubMed)
(53) DHEA, DHEAS and PCOS by Goodarzi MO1, Carmina E2, Azziz R3.(PubMed)
(54) Adrenal androgen excess and body mass index in polycystic ovary syndrome by Moran C1, Arriaga M, Arechavaleta-Velasco F, Moran S.(PubMed)
(55) Superactive human leptin antagonist reverses leptin-induced excessive progesterone and testosterone secretion in porcine ovarian follicles by blocking leptin receptors by Gregoraszczuk EL1, Rak A.(PubMed)
(56) Reproduction in hens: is testosterone necessary for the ovulatory process? by Rangel PL1, Gutierrez CG2.(PubMed)
(57) The value of sex hormone binding globulin (SHBG) in predicting treatment response in polycystic ovary syndrome (PCOS) by Wassell J1, Michail M, Soliman N, Wardle PG.(PubMed)
(58) Effects of metformin treatment in women with polycystic ovary syndrome depends on insulin resistance by Nawrocka J1, Starczewski A.(PubMed)
(59) Serum luteinizing hormone level and luteinizing hormone/follicle-stimulating hormone ratio but not serum anti-Müllerian hormone level is related to ovarian volume in Korean women with polycystic ovary syndrome by Chun S1.(PubMed)
(60) [Effect of luteinizing hormone vs follicular stimulating hormone ratio on anti-Müllerian hormone secretion and folliculogenesis in patients with polycystic ovarian syndrome].[Article in Chinese] by Li Y1, Wei LN, Xiong YL, Liang XY.(PubMed)
(61) Thyroid disorders in polycystic ovarian syndrome subjects: A tertiary hospital based cross-sectional study from Eastern India by Sinha U1, Sinharay K, Saha S, Longkumer TA, Baul SN, Pal SK.(PubMed)

(62) Studies of cardiovascular risk factors in polycystic ovary syndrome patients combined with subclinical hypothyroidism by Pei YJ1, Wang AM, Zhao Y, Yan L, Li M, White RE, Han GC.(PubMed)
(63) Polycystic ovary syndrome and chronic autoimmune thyroiditis by Novais Jde S1, Benetti-Pinto CL, Garmes HM, Jales RM, Juliato CR.(PubMed)
(64) Association of thyroid-stimulating hormone with insulin resistance and androgen parameters in women with PCOS by Dittrich R1, Kajaia N, Cupisti S, Hoffmann I, Beckmann MW, Mueller A.(PubMed)

(65) [Association between levels of serum leptin and insulin resistance in patients with polycystic ovary syndrome].[Article in Chinese]by Cheng X1, Guo J2, Xie J3.(PubMed)
(66) [Clinical study on treating insulin resistance and promoting ovulation in polycystic ovary syndrome].[Article in Chinese]by Liu ZA1, Xue YM, Chen LX, Cai Q, Chen H, Zhang J, Cui QH, Ge J, Yuan T.(PubMed)
(67) Randomized clinical trial evaluating metformin versus oral contraceptive pills in the treatment of adolescents with polycystic ovarian syndrome by Al-Zubeidi H, Klein KO.(PubMed)
(68) Randomized controlled trial evaluating response to metformin versus standard therapy in the treatment of adolescents with polycystic ovary syndrome by Allen HF1, Mazzoni C, Heptulla RA, Murray MA, Miller N, Koenigs L, Reiter EO.(PubMed)

Thursday 26 March 2015

The Best of smoothie's recipes: Apple-ginger splitz

Weight Loss the Easy Ways 
Andrea Albright Featured on Health and Fitness Jan. 2015
will Personally Coach You How to Get There The Easy Way

Posted By Kyle J. Norton
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.

The (safe, nutritious, easy to prepare snacks for any occasion) ultimate allergy-free snack cookbook by Judi and Shari Zucker, Square one publishers. Over 100 kid -friendly recipes for the allergic child.

The combination of Granny Smith apple and carrot juice give this refreshing drink a sweet-tart taste, while the ginger gives a flavorful spark.
Yield 2  servings, about 8 ounces each

3 Granny Smith apples and cut into small chunks (about 2 cups)
1 cup carrot juice
1/4 teaspoon ground ginger
1 tablespoon lime juice
1/2 cup sparkling water

1. Place all ingredients in a blender
2. Blend on high speed or until mixture is smoothed for about 1/2 minute or until mixture is smooth and the ice well crushed.
3. Pour in glass over ice, garnish with a slice green apple and serve immediately.

Change it up..... For a sweet drink, use a sweet variety of apple, such as Delicious (red or golden), Fuji, Gala.....
For Over 1000 recipes http://kylejnorton.blogspot.ca/p/recipes.html

Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer

The Holistic prevention, management and treatment of Polycystic Ovarian Syndrome: The Risk Factors(Revised edition with Citations)

Weight Loss the Easy Ways
Andrea Albright Featured on Health and Fitness Jan. 2015
will Personally Coach You How to Get There The Easy Way

If You Are Looking For a SoulMate
Celebrity Patti Stanger Will Coach You To Get Him/Her
and Keep Him/Her for Good,The Simple Way

By Kyle J. Norton Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.




                                     Polycystic Ovarian Syndrome

Polycystic Ovarian Syndrome is defined as endocrinologic diseases among reproductive-age women caused by undeveloped follicles clumping on the ovaries that interferes with the function of the normal ovaries associated with a high risk for metabolic disorder(1) as resulting of enlarged ovaries(2), leading to hormone imbalance(excessive androgen and anti-müllerian hormone (AMH) )(1)(3)(4)(5), induced Hirsutism(6)(7), reproductive disorder(10(12)), risks of type 2 diabetes(9)(10)(11), metabolic syndrome(10)(12) and early cardiovasular disease(8)(13), acne(10)(14), endometrial cance(18)(19),weight gain and obesity(15)(16)(17). The syndrome effects over 5% of women population or 1 in 20 women.
Unfortunately, according to studies, women with PCOs after the reproductive age, are associated to  continuously increase risk of type II diabetes, with no increasing altered glucose tolerance(20), CVD and hypertension(21).


                                                      The Risk factors


1. Family history
Risk of PCOs is increase if your mother or sister has PCOS(29). According to North Staffordshire Hospital, polycystic ovaries are highly prevalent within families as an autosomal dominant trait, in the analysis of 29 polycystic ovary syndrome and 10 control families(30).

2. Reproductive age women
Polycystic ovary syndrome (PCOS) affects 4% to 18% of reproductive-aged women(31)

3. Environment risks
a. Eating plastic-packaged food(32), fruit with pericarp(32) and drinking alcohol(32) were associated to the independent risk factors for PCOS. According to the Second Affiliated Hospital of Nanjing Medical University, risks of PCOs increased with the use of  disposable plastic cup for drinking, cooking oil fume and indoor decoration(33).
b. Exposure to industrial products such as Bisphenol A (BPA)(36)were found to exacerbate the clinical course of PCOS(34) as they exhibited impairment of normal reproductive function and metabolic regulation(35).

4. Dietary factor
Over-nutrition with foods in advanced glycated end products (AGEs) is found to associated to risk of PCOs(34).

5. Metabolic perturbations begin early in adolescence are also found to elevate risk of PCOs(37).

6. Psychotropic medication
Prolonged period uses of psychotropic drugs such as  mood stabilizers, lithium are also induced higher risk of PCOs(38). Women with epilepsy are also at risk of developed polycystic ovary syndrome (PCOS) if treated by valproate sodium (VPA) therapy(39)(40).

7. Genetic mutations
Although it is uncleared, genetic mutation of certain genes may be associated to the risk of PCOs, according to studies, such as the zona pellucida 4 (ZP4)(41) gene, polymorphism of FXIIIVal34Leu gene(42), C/T single nucleotide polymorphism at exon 17(43), single nucleotide polymorphism-56 of calpain-10 gene(44), vaspin rs2236242 polymorphism(45), etc.

Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months   


References
(1) Adiposity and metabolic dysfunction in polycystic ovary syndrome by Sam S.(PubMed)
(2) A "kiss" before conception: triggering ovulation with kisspeptin-54 may improve IVF by Young SL.(PubMed)
(3.) Androgen hyperfunction and excessive heterosexual hair growth in women, with special attention to the polycystic ovarian syndrome by Lunde O1.(PubMed)
(4) Expression of anti-Müllerian hormone in letrozole rat model of polycystic ovary syndrome by Du DF1, Li XL, Fang F, Du MR.(PubMed)
(5) [Serum levels of anti-muller hormone in women with polycystic ovary syndrome and healthy women of reproductive age].[Article in Bulgarian] by Parahuleva N, Pehlivanov B, Orbecova M, Deneva T, Uchikova E.(PubMed)
(6) [Current opinions on the etiology and pathophysiology of hirsutism].[Article in Polish] by Krysiak R1, Kedzia A, Okopień B.(PubMed)
(7) The clinical evaluation of hirsutism by Somani N1, Harrison S, Bergfeld WF.(PubMed)
(8) Polycystic ovary syndrome and insulin: our understanding in the past, present and future by Mayer SB1, Evans WS, Nestler JE.(PubMed)
(9) Association of mean platelet volume with androgens and insulin resistance in nonobese patients with polycystic ovary syndrome by Dogan BA1, Arduc A2, Tuna MM1, Karakılıc E1, Dagdelen I1, Tutuncu Y1, Berker D1, Guler S1.(PubMed)
(10) Approach to the patient: contraception in women with polycystic ovary syndrome by Yildiz BO1.(PubMed)
(11) Polycystic ovarian syndrome (PCOS): a significant contributor to the overall burden of type 2 diabetes in women by Talbott EO1, Zborowski JV, Rager JR, Kip KE, Xu X, Orchard TJ.(PubMed)
(12) Prevalence of vitamin D deficiency in Slovak women with polycystic ovary syndrome and its relation to metabolic and reproductive abnormalities by Figurová J1, Dravecká I, Javorský M, Petríková J, Lazúrová I.(PubMed)
(13) Role of Insulin Sensitizers on Cardiovascular Risk Factors in Polycystic Ovarian Syndrome: A Meta-Analysis by Thethi TK1, Katalenich B2, Nagireddy P3, Chabbra P4, Kuhadiya N5, Fonseca V1.(PubMed)
(14) Acne in hirsute women by Lumezi BG1, Pupovci HL1, Berisha VL1, Goçi AU2, Gerqari A3.(PubMed)
(15) Obesity and polycystic ovary syndrome by Naderpoor N1, Shorakae S, Joham A, Boyle J, De Courten B, Teede HJ.(PubMed)
(16) Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan by Teede H1, Deeks A, Moran L.(PubMed)
(17) Metabolic Evidence of Diminished Lipid Oxidation in Women With Polycystic Ovary Syndrome. by Whigham LD1, Butz DE2, Dashti H3, Tonelli M3, Johnson LK1, Cook ME2, Porter WP4, Eghbalnia HR5, Markley JL6, Lindheim SR7, Schoeller DA8, Abbott DH9, Assadi-Porter FM10.(PubMed)
(18) Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis by Barry JA1, Azizia MM1, Hardiman PJ2.(PubMed)
(19) Risk of cancer among women with polycystic ovary syndrome: a Danish cohort study by Gottschau M1, Kjaer SK2, Jensen A1, Munk C1, Mellemkjaer L3.(PubMed)
(20) Polycystic ovary syndrome: metabolic consequences and long-term management by Carmina E1.(PubMed)
(21) Arterial stiffness is increased in asymptomatic nondiabetic postmenopausal women with a polycystic ovary syndrome phenotype by Armeni E1, Stamatelopoulos K, Rizos D, Georgiopoulos G, Kazani M, Kazani A, Kolyviras A, Stellos K, Panoulis K, Alexandrou A, Creatsa M, Papamichael C, Lambrinoudaki I.(PubMed)
(29) Hormonal abnormalities in first-degree relatives of women with polycystic ovary syndrome (PCOS) by Lenarcik A1, Bidzińska-Speichert B, Tworowska-Bardzińska U, Krępuła K.(PubMed)
(30) Polycystic ovaries are inherited as an autosomal dominant trait: analysis of 29 polycystic ovary syndrome and 10 control families by Govind A1, Obhrai MS, Clayton RN.(PubMed)
(31) Lifestyle changes in women with polycystic ovary syndrome. Moran LJ1, Hutchison SK, Norman RJ, Teede HJ.(PubMed)
(32) Environmental risk factors for women with polycystic ovary syndrome in china: a population-based case-control study by Zhang J1, Liu XF1, Liu Y1, Xu LZ1, Zhou LL1, Tang LL1, Zhuang J1, Li TT1, Guo WQ2, Hu R3, Qiu DS3, Han DW3.(PubMed)
(33) [Analysis of environmental factors and polycystic ovary syndrome]. [Article in Chinese] by Huang WJ1, Liu JY, Li LN.(PubMed)
(34) Phenotypes and enviromental factors: their influence in PCOS by Diamanti-Kandarakis E1, Christakou C, Marinakis E.(PubMed)
(35) Industrial endocrine disruptors and polycystic ovary syndrome by Palioura E1, Diamanti-Kandarakis E.(PubMed)
(36) Bisphenol A (BPA) and its potential role in the pathogenesis of the polycystic ovary syndrome (PCOS) by Rutkowska A1, Rachoń D.(PubMed)
(37) PCOS in adolescence and type 2 diabetes by Carreau AM1, Baillargeon JP.(PubMed)
(38) [Adverse events of psychotropic drugs]. [Article in Japanese] by Watanabe K, Kikuchi T.(PubMed)
(39) [Characteristics of women with epilepsy who developed polycystic ovary syndrome owing to the therapy with valproate sodium]. [Article in Japanese] Minagawa K1, Watanabe T, Oyanagi R.(PubMed)
(40) A meta-analysis of polycystic ovary syndrome in women taking valproate for epilepsy by Hu X1, Wang J, Dong W, Fang Q, Hu L, Liu C.(PubMed)
(41) Study on the zona pellucida 4 (ZP4) gene sequence and its expression in the ovaries of patients with polycystic ovary syndrome by Meczekalski B1, Nawrot R, Nowak W, Czyzyk A, Kedzia H, Gozdzicka-Jozefiak A.(PubMed)
(42) Association study of polymorphism of FXIIIVal34Leu gene and polycystic ovary syndrome by  Wang X1, Yang Y1, Huang Y2, Wang Q3.(PubMed)
(43) [Correlation between single nucleotide polymorphism of insulin receptor gene with polycystic ovary syndrome]. [Article in Chinese] by Chen ZJ1, Shi YH, Zhao YR, Li Y, Tang R, Zhao LX, Chang ZH.(PubMed)
(44) [Relationship between single nucleotide polymorphism-56 of calpain-10 gene and glucose and lipid metabolism in polycystic ovary syndrome patients]. [Article in Chinese] by Diao XH1, Shi YH, Gao Q, Wang LC, Tang R, Chen ZJ.(PubMed)
(45) Association between vaspin rs2236242 gene polymorphism and polycystic ovary syndrome risk by Kohan L1, Zarei A2, Fallahi S3, Tabiee O4.(PubMed)

The Best of smoothie's recipes: California sunshine sparkler

Weight Loss the Easy Ways 
Andrea Albright Featured on Health and Fitness Jan. 2015
will Personally Coach You How to Get There The Easy Way

Posted By Kyle J. Norton
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.

The (safe, nutritious, easy to prepare snacks for any occasion) ultimate allergy-free snack cookbook by Judi and Shari Zucker, Square one publishers. Over 100 kid -friendly recipes for the allergic child.

Very light.... very refreshing
Yield 2  servings, about 8 ounces each

2/3 cup rice milk
1 cup fresh or frozen bluebberries
1 cup seedless grapes
1 tablespoon brown rice syrup or honey
1 cup sparkling water

1. Place blueberries, grapes and brown rice syrup in a blender and blend on medium speed for about 1 minute.
2. Add sparkling water and stir on low speed for a few seconds.
3. Pour in glass over ice and serve.
For Over 1000 recipes http://kylejnorton.blogspot.ca/p/recipes.html

Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer