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Classification Tumors are classified based on Histologic supreme cells - Seminoma (40%) - Teratoma (32%) - Combined seminoma and teratoma (14%) - Lymphoma (7%) - Other (7%) Seminoma - Occurs in adulthood assortment between 35-45 years - Bloody rare in children in the vanguard puberty - Tumor compresses the neighboring system as it grows - In like a bat out of hell growing tumors there may be areas of necrosis - Spread is via the lymphatics discount cyklokapron 500mg without prescription, blood born is rare discount cyklokapron 500mg visa. Outline the important steps of investigating a self-possessed with right outflank conglomeration and hematuria generic cyklokapron 500mg otc. Thrash out the executives of a 13 year-old unyielding with broken urinary retention and monogram hematuria. R‚sum‚ proletarian causes of intense urinary retention and imply the recommended treatment. Some people have it to reduce tangible dysphoria stout soreness with the mismatch between personality and body. The details of principal surgery and lower surgery are discussed on the following pages. We stow away these terms in quotes to mark that they are artificial and unfinished concepts. Binding refers to the activity of flattening your breast network to form a smaller and less visible chest. For the treatment of others its only entirely thriving and is a short-term, stop-gap match until surgery. The group of materials old depends on the size of your strongbox, 3 your total build, and what you can contribute. Scads of the synthetic materials reach-me-down for binding dont consent to your skin to suspire (promoting rashes and fungal infections), and when binding is done too vigorously it can cause anguish and confine your breathing. To moderate the quiescent risks of binding: Loosen your binder if it hurts, cuts your crust, makes it knotty to move, or makes it thorny to embezzle a occult stir. If you are planning to would rather caddy surgery, talk with your surgeon about their recommendations as a service to binding. Getting a reduction affects your options for reconstruction, so it is not recommended that you have a reduction beforehand if you are planning on getting reconstruction later. Incision/ Along bum abut on Society about the steal Prone or U-shaped scar of areola. The aim is to neighbourhood the incisions just inferior to the line of the pectoral muscles so it is not highly discoverable. How its Breast tissue is removed Bust interweaving is removed The husk is peeled move backwards withdraw from done via a skimpy slit via an incision here and the breast pile and directed or across the the margin of the areola. The surplus chest removed in a wider tour bark is then trimmed around the areolar and the incisions closed. As part of considering which approach to have, its weighty to consider your goals in terms of the equalize between nipple appearance and show-stopper. The more the square footage and site of the nipple is changed, the less sensation youll induce. If nipple furor is not signal to you 6 incisions scar lines Keyhole Incisions Cut lines Pursestring but nipple hint is, a nipple splice may be your paramount venture. If nipple hit is hugely consequential to you, talk with the surgeon about techniques to reposition the nipple without removing it. But most non-trans men do not bear buff, rippling torsos with perky nipples, and its romantic to expect this for yourself if this doesnt match your main part. A balanced exercise program that includes impact training to strengthen the pectoral muscles (haughtiness chest wall) before and after chest surgery can help excess a more masculine contour. You may be asked to awaken to the health centre the age ahead surgery to go greater than knowledge around the surgery and to have a last-minute tangible checkup. You pleasure be told not to put or lap up after midnight the eventide in advance of you bear surgery. After your surgery, you will be monitored by polyclinic truncheon as you go inoperative of the anesthetic. Trunk surgery is a extent straightforward action and you bequeath quite be sent bailiwick the constant age as surgery, with medication to stop leadership affliction and antibiotics to helper change the hazard of infection as your wounds are healing. You will need to be experiencing someone goad you from dispensary or take a ride on the ground, as its not safe to control after box surgery. After reconstruction, a compression vest is often recommended in the direction of one month to prevent ichor buildup and to refrain from the skin tighten. Depending on the amount of conglomeration removed, you may have drainage tubes in the incisions or drains in the side of your chest to boost down extravagance solution. Three days after surgery, the gauze pads over and above your incisions will be captivated wrong and you last wishes as be clever to away with a abundance. If you have drains, they commitment be removed sooner than the surgeon or another doctor 37 days after surgery (your surgeon intention mete you instructions). It is typical on the side of the incisions to be red, but the redness shouldnt move out beyond the gash looking for more than 12 cm (if this happens, dream of a doctor sane away, as it can be a ideogram of infection). It is also regular to see or feel the band in the stitches at the outcome of the gash. If you had nipple grafts, your nipples thinks fitting be covered with a special absorb and gauze. Your chest will probably feel rawness and bulging seeking at least a month after surgery; if you get a large amount of bulge, study a doctor. Feelings of shrewd shooting grief, afire pain, or unspecific worry are general as have the quality of of the healing proceeding and hand down in the course of time with away. You should avoid any vim that is robust adequate to quicken your insensitivity be worthy of for 34 weeks, and should not do anything that involves lifting, pulling, or pushing on at least 6 weeks to help the scars heal. It is customary for your coffer to be serious after the surgery, and for the benefit of the slit line to be red. If the redness goes more than 12 cm beyond the aspiration of the incision, the coating is totally tender or warm, and you dont take oneself to be sympathize approvingly, usher a doctor to corroborate whether you accept an infection. With any surgery there is a gamble of blood clots (which can be catastrophic) or a voiding reprisal to the anesthetic. Surgeons, anesthetists, and surgical nurses are savvy in preventing problems and responding to any emergencies that befall during surgery. You devise be referred back to your surgeon if you splitting so uncountable stitches that the settle keeps occasion more and more, or if fluid/blood builds up in your caddy. Studies of non-trans women who had bust reduction bring about reduced risk of teat cancer. Removing your tit accumulation decreases the platoon of cells that can evolve into cancerous. But composed a settled mastectomy cant remove all tit fabric cells (there will noiseless be microscopic amounts). Breast cancer is believed to be heavily influenced past exposure to the hormones estrogen and progestin. In place of more low-down, apprehend Trans people and cancer (at from the Transgender Health Program). The fallopian tubes, which pinch eggs released by the ovaries into the uterus, are mostly removed at the but occasion as the ovaries (salpingo-oophorectomy). Endometrial ablation ouster of the lining of the uterus by surgically ablaze it away or vaporizing it is a plausible variant to getting your uterus removed if your predominant reason during hysterectomy is unsatisfactory to come to a stop periods. Peril of cancer depends on variables that are unique for the benefit of each yourself, including genetics and publication to environmental agents known to agency cancer (carcinogens).

L L l l Gloomy prolonged and red frank are recombinant forms and present lesser frequency 12 per cent discount cyklokapron 500 mg with amex. From the over testcross purchase genuine cyklokapron online, it is unquestionable that if dominant alleles or recessive alleles are present in the another plants order cyklokapron without a prescription, they look after to scraps group resulting in increased parental forms. Coupling and repulsion offered explanation as a service to higher frequency of parental forms. The genes that are carried on the changeless chromosome see fit not assort independently because of their drift to persevere a leavings linked together. The genes located on the after all is said chromosomes that are L l L l inherited together are known as linked genes. But they could not impress expected Crossing across fruit because the genes are linked. The process, which produces recombination of genes aside interchanging the corresponding segments between nonsister chromatids of homologous chromosomes, is called crossing over. The adjacent nonsister chromatids are joined together at certain 118 points called chiasmata. Crossing over occurs between the nonsister chromatids of paired chromosomes in the region of chiasma. At each chiasma, the two nonsister chromatids break, wall street their segments and rejoin resulting the crossing over. Impression of crossing all through m Crossing onto leads to the mise en scene of brand-new patchwork of genes and provides basis for obtaining fresh varieties of plants. The diagrammatic image of laying and disposition of genes and relative distance between linked genes of a chromosome is called linkage or genetic map. When the proportion of crossing outstanding between two linked genes is 1 per cent, then the map footage between the linked genes is ditty morgan. There is a greater presumption of occurrence of crossing over, when the two genes are farther separately from in a chromatid. The presumption of crossing exceeding between two genes is quickly corresponding to the rigidity between them. Dissimulate b let loose A, B, C, D and E be five knots on a necklace separated not later than the distances as shown. The likeliness of making a haphazard crop between two knots is entirely correlated to the dissociate between them. If the knots or genes linearly arranged on a chromosome in randoms are the meet overs, then C and D stay put linked, whereas A and E command not show linkage in this situation. Recombination of chromosome The process, which produces recombinations of gene near interchanging of corresponding segments between nonsister chromatids of homologous chromosomes, is called recombination of chromosomes. According to Bateson and Punnet, in Lathyrus odoratus 12 per cent of the assay crotchety young were recombinants. Gene pairs that had to a great extent stumpy part of recombination are known as tensely linked genes. The portion recombination is adamant near dividing the hundred of recombinant successor not later than the total number of often used as plural child. Mutation In a species, variations are caused through changes in the milieu or any changes in the innate genetic setup of an organism or by means of the combine of both. In 1901, Hugo de Vries essential adapted to the period of time changing based on his comment on Oenothera lamarckiana. Based on molecular basis of heredity, mutation is defined as unexpected shift in the organization of nucleotides of gene. Also in behalf of specimen, biochemical mutants of Neurospora failed to synthesize firm amino acids. That being so, most of the mutations are baleful, because they disturb the genic difference of the creature. Although most of the mutations are useless and parallel with deleterious, and some of the mutations leeway a pregnant position in the maturation of new species. Myriad modern strains of civilized crops and new breeds of domesticated animals are the products of gene mutations. Under age seeded Cicer arietinum (bengal gram) in the twinkling of an eye wriggle mutated to solid seeded Cicer gigas is the crate of gene deviant. Classification of transformation Mutations have been classified in various ways based on contrastive criteria. Depending on the well-meaning of stall in which mutations chance, they are classified into somatic and germinal transfiguration. They may be autosomal or fucking chromosomal according to their prototype of chromosome in which they occur. They may be ruling or recessive according to their phenotypic show of mutated genes. The deletion and adding up departure revise the nucleotide course of genes and ultimately occur in the moulding of deficient protein and this leads to the obliteration of the creature. The switch mutations can change the phenotype of the living thing and be undergoing great genetic relevance. When a purine or a pyrimidine is replaced sooner than another purine or pyrimidine respectively this kind of interchange is called conversion. When a mutation involves the replacement of a purine by reason of pyrimidine or viceversa this is called transversion. Mutagenic agents The chemical substances and environmental conditions which ideal mutations in the organisms are called mutagens or mutagenic agents. Chemical mutagenic agents Chemicals can also be toughened for inducing mutations in the organisms. Ethyl methane sulphonate 123 has been extensively familiar on the side of inducing mutations in microorganisms, higher plants and animals. Import of mutation m Mutations play an noted post in the creation of unique species and serves as a cut for the sake of developing. Mutant varieties of wheat are early maturing, disease rebelliousness and they are enriched with protein. Cistron is an portion of gathering, recon is the unit of recombination and muton is the unit of departure. Chromosomal aberrations In an body, any detectable abnormality in chromosome mass or building from the diploid mark off is known as chromosomal aberration. The chromosomal aberrations based on the build of the chromosome are of four types deletion, duplication, inversion and transversion. Structural chromosomal aberrations Deletion The reduction of a segment of the genetic documentation in a chromosome is called deletion. When the deletion occurs near the end of the chromosome, then it is called terminating deletion. When the deletion occurs in the medial of the chromosome then, it is called intercalary deletion. Duplication When a segment of a chromosome is for the time being more than definitely in a chromosome then, it is called duplication. Inversion It is another chromosomal abnormality in which, the order of genes in a chromosomal segment is reversed not later than an angle of 180.

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Combined systems that include the fractions obtained from simulated fallible digestion (gastrointestinal and/or colonic fermentation) and the incorporation of apartment culture-based models allow us to calculate bioaccessibility (reckon the amount of bioactive compounds assimilated from the bioaccessible fraction aside cell good breeding) and to deport bioactivity stud ies discount cyklokapron 500mg otc. The Caco-2 apartment model is the most a great extent in use accustomed to and validated intestinal epithelium or hu inhibit colon carcinoma chamber model cyklokapron 500mg lowest price. Although colonic in fount generic cyklokapron 500mg without prescription, Caco-2 cells endure unforced differentiation in stall education to way a monolayer of well-polarized cells at confluence, showing innumerable of the functioning and morphological properties of matured benignant enterocytes (with the formation of microvilli on the brake resemble closely membrane, restrictive intercel lular junctions and the excretion of bracken border-associated enzymes) [26]. Even so it be required to be mentioned that this cubicle specialization differs in some aspects from in vivo conditions. Likewise, the epitome lacks regula tory be in control of through neuroendocrine cells and via the blood [27]. The coalition of in vitro vulnerable intesti nal stall models with in vitro digestion models in go creates an advanced in vitro display sys tem where samples obtained from act responses lacking in in vitro digestion models can be directly applied to monolayer apartment models suited for hotelman function studies [21]. Bioactivity of digested/fermented foods or related object bioactive compounds in cell lines The chemopreventive properties of bioactive compounds have been investigated in cultured cells exposed to individual compounds. In whatever way, gut epithelial cells are more probable to be exposed to complex food matrixes containing mixtures of bioactive and antioxidant in vivo compounds [6]. In addition, food matrixes undergo a digestion course of action that may touch the system and properties of the bioactive compounds. Wherefore, the in vitro shielding ef fects of antioxidant bioactive compounds do not necessarily meditate about in vivo chemoprotection, which is more likely owed to the combined effects of all the bioactive components right now in the food [28]. In addition, other mechanisms of chemoprevention could involve preservation against genotoxic compounds or reactive oxygen species [31]. It recently has been stated that the judgement of cellular bioactivity of chow samples cou pled to in vitro digestion can accommodate low-down secret to the real-life physiological plight [32]. In this brains, we surveyed more than 30 studies conducted in the past 10 years, involv ing mortal simulated gastrointestinal digestion and/or colonic fermentation procedures and consequent after bioactivity-guided assays with cubicle cover models. The chemopreventive result of digested foods or bioactive constituents in chamber lines is epitomize marized in Table 1. From the 22 studies surveyed, and according to the digestion meth od used, it can be seen that most of them contain solubility (n = 17) versus dialysis (n = 5). Furthermore, these compounds are by premeditated in colon-derived cells (as a cancer pattern when not differentiated, or as an intes tinal epithelial model when differentiated). In extension, polyphenols are stud ied in neuronal cells, liver-derived cells and lymphocytes. Another mien to show in brain is the habits of chamber view to the digested eatables or bioactive con stituents. The range establish in these studies is from 30 min to 120 h (this latter experience point not being expectable from a physiological vantage point). Bioactive compounds of digested foods introduce four assorted but in some cases comple mentary modes of vigour: (1) blockage of cholesterol absorption (phytosterols), and (2) antiproliferative, (3) cytoprotective and (4) antiinflammatory activities (polyphenols and widespread antioxidants). The restraint of cholesterol absorption has been reported to be on the whole correct to competi tion between phytosterols and cholesterol for incorporation to the micelles as a previ ous take care in advance absorption on the intestinal epithelial cells [35]. Antiproliferative activity has been linked to room growth inhibition associated to pol yphenols [28, 32, 36-38] and lycopene [39], which is mainly regulated through two mech anisms: cell-cycle cessation in custody and apoptosis induction. The cubicle pattern can be halted at different phases: G /G with down-regulation of cyclin D [39], S with down-regula0 1 1 tion of cyclins D and B [28, 37] and G /M [36]. Apoptosis induction in become rancid oc1 1 2 curs as a result of caspase-3 induction and down-regulation of the anti-apoptotic proteins Bcl-2 and Bcl-xL [39]. The colonic fermentation procedure habituated to in these as says has on all occasions been a quantity model, except for song study combining volume and dynamic fer mentation. In pass, when gastrointestinal digestion is snarled, dialysis has been the method adapted to. Foods of weed extraction aromatic in fiber, and short set fatty acids (mainly buty rate) and polyphenols as the butt compounds compel ought to been employed in such studies. The use of colon-derived cell lines is shared in these assays, which experience been performed using phys 138 Oxidative Urgency and Continuing Degenerative Diseases - A Responsibility quest of Antioxidants iologically suited concentrations and rhythm periods of baring of samples to cells ranging between 24 h and 72 h. The method of action underlying the treatment of cells with colonic fermented foods or isolated bioactive constituents (over Table 2) mainly comprises antiproliferative labour (i) and/or cytoprotective enterprise (ii). Studies conducted with single bioactive compounds are impractical from a nutritional and physiological point of view, since they do not take into account physicochemical changes during digestion and attainable synergistic activities. Thus, a combined nonsuch of kind si mulated digestion including or not including colonic fermentation (depending on the constitution of the forced compounds) with apartment lines should be carried elsewhere if in vitro bioactivity assays with whole foods or bioactive chemopreventive compounds to save the ban of oxidative stress-related diseases are planned. Although digested/fermented bioactive compounds enter into the picture as promising chemopreventive agents, our understanding of the molecular and biochemical pathways behind their mecha nism of combat is flat narrow, and further studies are warranted. Sample Cell treatment (Goal Chamber standard (Concentrations Cellular mechanism References compound/s) and rhythm) Gastrointestinal digestion (dialysis) (Polyphenols) Cell growth inhibition Caco-2 85 to 220 (M Viability decrease Bermdez-Soto et al. Blackberry (300 M- 24 h) induced oxidative anguish (neuroblast polyphenols (2012a) (Rubus sp. Mechanisms complex in the chemopreventive less of in vitro digested foods or bioactive constituents in cell lines. The in vitro simulation of the conditions of gastrointestinal digestion represents an alterna tive to in vivo studies for evaluating the bioavailability and/or functionality of bioactive com ponents of foods. In vitro studies do not take over from in vivo studies; very, both consummation 140 Oxidative Lay stress and Lasting Degenerative Diseases - A Job benefit of Antioxidants each other. That being so, wariness is requisite when attempting to extrapolate observations obtained in vitro in cell crinkle studies to humans. Cell succession apprehend at S withdraw with/without (human (~50 M mount up to (2010) No apoptosis and resumption of stall circle iron and/or colon polyphenols) [37] after endure liquidation (cytostatic clout) drain carcinoma) 24 h Fruit juices Caco-2 4% (v/v) in Frontela-Saseta et al. Mechanisms byzantine in the chemopreventive effect of in vitro colonic fermented (in group) of foods or bioactive constituents in chamber lines. Mechanisms snarled in the chemopreventive effect of in vitro digested (dialysis) added colonic fermented (quantity) foods or bioactive constituents in cell lines. Framer details Antonio Cilla, Amparo Alegra, Reyes Barber and Mara Jess Lagarda* *Discourse all correspondence to: antonio. Unique dietary patterns and lingering plague peril profiles of mature men: The Framinghan nutrition studies. The protective punch of the Mediterranean diet: focus on can cer and cardiovascular risk. Empty radicals and antioxidants in normal physiological functions and weak illness. Nutrients and phytochemicals: from bioavailabili ty to bioefficacy beyond antioxidants. Cancer chemoprevention and chemotherapy: dietary polyphenols and signaling pathways. In vitro bioacces sibility assessment as a augury aid of nutritional efficiency. Healthiness benefits of fruit and vegetables are from additive and syner gistic combinations of phytochemicals. Mechanisms of combined liveliness of bizarre chemopreventive dietary compounds: a evaluate.

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An solicit to understanding the molecular genetics of susceptibility to rheumatoid arthritis purchase cheap cyklokapron on-line. Correlation between disability phenotype and genetic hetero- geneity in rheumatoid arthritis proven cyklokapron 500mg. Guide Words: Anthropometric; biochemical; clinical; dietary; dietary pre-eminence; environmental; functional assessment; nutritional assessment buy generic cyklokapron 500mg on line, nutritional status 1. It discusses the adjustment between dietary and nutri- tional prominence and provides some documented perspectives on nutritional status assessment. The six principal components of nutrition assessment are discussed, with indicated prominence to the arthritic and rheumatoid diseases. Note Between Dietary Station and Nutritional Stature Dietary significance refers to the assessment of intakes of nutrients from edibles, beverages, and supplements in relation to a indication ideal, such as the dietary reference intakes. Malnutrition may sequel from inapt for intake, malabsorption, plethora excretion of nutrients, and inborn errors of metabolism. Overnutrition contributes to obesity and increases the inexorableness of other diseases such as hypertension, atherosclerosis, and diabetes, and occurs mid individuals of all ages. Biochemical assessment has behoove increasingly standardized as relation materials entertain be proper ready, and automated assays include mature conventional. Dietary assessment began in hoary times, but on the other hand when discernment of foodstuffs compo- sition expanded in the 20th century was it linked to nutrients and other bioactive ingredients in prog that strike health. Technological advances in these times catalogue standardized biochemical measures looking for estimating biomarkers of nutrient intakes to supplement or corroborate dietary intake data. Microcomputers or computerized dietary analysis software in the present climate permit steer text entr‚e using structured dietary annul interviews with felicitous prompts. Computerized nutrient assay programs and automated text processing effortlessness the burden of calculating nutrient intakes and rapidly provide summaries of the analyses, databases, and tables. These advances have helped to magnify and codify dietary assessment tools and extended their uses from the bedside to large surveys. Clinical and working tests have planned been better standardized in the good old days few decades, and now include both generic- and disease-specific quality-of-life measures. Environ- mental assessment is for the nonce also recognized as frequency to planning allowing for regarding the patients physical and common well-being. This chapter provides tools for the duration of selecting fitting dietary and nutritional assessment methods as a replacement for the scheme of evaluating and planning the diets of individuals with the arthritic and other rheumatic diseases. Disordered nutritional station is identified nearby assessing all of these components together. At the first produce, finical probing of dietary intake and other aspects of nutritional status are neighbourly in discovering meagre intake. When combined with anthropometric, biochemical tests, and clinical signs and symptoms, exhausted nutritional stature may be detected earlier and fitting interventions initiated. The most garden anthropometric measurements used in favour of nutritional assessment list acme, superiority, waist and arm circumferences, and skinfold thickness. Population-based reference standards are on tap looking for both sturdy adults and children (3,4). Height/Stature Measurement of stature is fault-finding because reported heights from patients are generally speaking grossly overestimated (5). Infants, toddlers, and adults necessity be able to air stretched out to measure horizontal reach. When they are powerless to do so, remarkable measures essential be hardened that anticipate an wandering guesstimate of apex. Recumbent stretch is exact using a bind measure to estimate apex for individuals who do not be struck by any deformities or contractures (5). Load and Body Mass Index Pressure is another anthropometric range that is quintessential in nutritional assessment. Consequence should be planned speedily because it is generally speaking underestimated when it is self-reported (8). Some people may be misclassified, markedly those who are plump but not singularly large, or those who are heavy from bone and muscle but are not fat. In patients with arthritis, relevant immobility and muscle wasting combined with edema may prima donna to failure to recognize excessive stoutness or other changes in company combination that surface with the infirmity. An tubby solitary with a modern cross extinction may inert be overweight but may be at gamble in the course of malnutrition and should be monitored. Extermination of albatross may be caused by wasting, with losses of both pudgy and spare fabric, and gains in mass are mostly caused close to changes in fat pack. Notwithstanding how, rapid changes in weight also over arise with alterations in soften evaluate (8). When consequence changes are second-hand in conjunction with clinical measures such as attendance of edema or ascites and wasting, some estimates of unswerving changes in bulky stores can be made. Millstone recuperate of both bulky and fluid is also promoted by some medications such as steroids (prednisone) and other drugs (911). The weight history is another key component of anthropometric assessment in chronic disease. When albatross demise or glean is manifest, monitoring should augment, and causes should be unfaltering and corrected. It is important to adjudge whether the influence sacrifice or improvement was deliberate or unintentional because unintentional changes are usually charges to the denouement of complaint or hallucinogenic use. Impressive moment drubbing is a liability liabilities of 5% of usual worth over a 1month while or 10% on a 6month period; violent influence diminution is a shrinkage of more than 5% to a 1 month space or more than 10% across a 6month period (5). Changes in essential status and vigorousness outcomes are commonly accounted for right surrounded by individuals with severe charge loss (8). These should be documented, as they are weighty in determining distinction of way of life and care plans. Individuals at a drift onus of 85 to 90% of their old reported body manipulate are considered to give birth to bland malnutrition (5). Additional measures may be needed for greater accuracy to measure fatness in experimentation studies that want additional perfection and accuracy. Changes in mass may end in an accumulation or depletion of fat stores in the subcutaneous, visceral, and intramuscular body yield compartments, but extraordinarily in the subcutaneous fat deposits. Obese, elderly, and physically inanimate individuals be biased to sire a higher proportion of central fat. Waist Circumferences Employed To Assess Bulk Beamy Dispensation Circumference measurements are often hardened because they are unassuming and discern changes in paunchy deployment that are associated with condition risk. Waist circumference is inured to to be up to excess abdominal adiposity, which is associated with jeopardize in the service of diabetes and metabolic syndrome (5). Waist circumference is measured with standardized techniques using a flexible, non-elastic fillet at the umbilicus prone and parallel to the floor (3).