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Returning unused human milk to erectile dysfunction doctor london order viagra sublingual 100 mg amex the mother informs her By following this standard erectile dysfunction purchase viagra sublingual 100mg line, the staff is able erectile dysfunction treatment vacuum constriction devices purchase 100 mg viagra sublingual otc, when necessary erectile dysfunction psychological treatment techniques purchase on line viagra sublingual, of the quantity taken while in the early care and education to prepare human milk and feed an infant safely, thereby program. Assessing the that are damaged by excessive heating during or after thaw knowledge, attitudes, behaviors and training needs related to infant ing from the frozen state (1). Currently, there is nothing in the feeding, specifcally breastfeeding, of child care providers. Matern research literature that states that feedings must be warmed Child Health J 12:128-35. Breast feeding: A guide for By following safe preparation and storage techniques, nurs the medical profession. Food, nutrition, and the and children can maintain the high quality of expressed young child. What to do if an may inform the child’s primary care provider; infant or child is mistakenly fed another woman’s expressed breast 5) Inform the parents/guardians that, depending milk. Red book: 2009 report of the Committee on Infectious guardians as well as the staff in the facility. If the child has not Storing Infant Formula been vaccinated or is incompletely vaccinated, then the Formula provided by parents/guardians or by the facility parent/guardian of the child who received the milk should should come in a factory-sealed container. The child should complete should be of the same brand that is served at home and the recommended childhood hepatitis B vaccine series as 167 Chapter 4: Nutrition and Food Service Caring for Our Children: National Health and Safety Performance Standards should be of ready-to-feed strength or liquid concentrate to safely, thereby reducing the risk of inaccuracy or feeding be diluted using water from a source approved by the health the infant unsanitary or incorrect formula. Powdered infant formula, though it is the least for both staff and parents/guardians must be available to expensive formula, requires special handling in mixing be determine when formula provided by parents/guardians will cause it cannot be sterilized. Formula cannot be served if it does not meet and safe handling and mixing is the manufacturer’s instruc the requirements for sanitary and safe formula. Before If a child has a special health problem, such as refux, or opening the can, hands should be washed. The can and inability to take in nutrients because of delayed develop plastic lid should be thoroughly rinsed and dried. Caregiv ment of feeding skills, the child’s primary care provider ers/teachers should read and follow the manufacturer’s di should provide a written plan for the staff to follow so that rections. If instructions are not readily available, caregivers/ the child is fed appropriately. Some infants are allergic to teachers should obtain information from the World Health milk and soy and need to be fed an elemental formula which Organization’s Safe Preparation, Storage and Handling of does not contain allergens. Infants should not be fed a formula different from the one the parents/guardians feed at home, as even minor differ Formula mixed with cereal, fruit juice, or any other foods ences in formula can cause gastrointestinal upsets and should not be served unless the child’s primary care pro other problems (6). Excessive shaking of formula may cause foaming that in creases the likelihood of feeding air to the infant. For bottles containing formula, any Formula should not be used beyond the stated shelf life contents remaining after a feeding should be discarded. Any prepared transporting and feeding infant formula prepared at home formula must be discarded within one hour after serving to and brought to the facility, and by ensuring that all infants an infant. An open be sanitary, properly prepared and stored, and must be the container of ready-to-feed, concentrated formula, or formula same brand in the early care and education program and at prepared from concentrated formula, should be covered, home. The caregiver/teacher should always follow manufacturer’s Water used for mixing infant formula must be from a safe instructions for mixing and storing of any formula prepara water source as defned by the local or state health depart tion. Warmed water Some infants will require specialized formula because should be tested in advance to make sure it is not too hot of allergy, inability to digest certain formulas, or need for for the infant. The appropriate formula should always be should shake a few drops on the inside of her/his wrist. For those infants bottle can be prepared by adding powdered formula and getting supplemental calories, the formula may be prepared room temperature water from the tap just before feeding. In Bottles made in this way from powdered formula can be those circumstances, either the family should provide the ready for feeding as no additional refrigeration or warming prepared formula or the caregiver/teacher should receive would be required. By following this standard, the staff is a scoop can be contaminated with a potential allergen from able, when necessary, to prepare formula and feed an infant another type of formula. Although many infant formulas are made from powder, the liquid preparations are diluted with Chapter 4: Nutrition and Food Service 168 Caring for Our Children: National Health and Safety Performance Standards water at the factory. Soy milk should be available for the children to feed, must be diluted with water. Adding recommends use of hypoallergenic formula (not soy-based too little water to formula puts a burden on an infant’s kid formula) for infants who are allergic to cow’s milk proteins. Soy-based formulas are appropriate for children with ga Adding too much water dilutes the formula. Because may interfere with an infant’s growth and health because it there is a lot of confusion in the public regarding cow’s milk provides inadequate calories and nutrients and can cause proteins and lactose intolerance, these indications should water intoxication. Water intoxication can occur in breastfed be documented by the child’s primary care provider and or formula-fed infants or children over one year of age who not based on parental/guardian possible misinterpretation are fed an excessive amount of water. Soy-based formulas are made from soy meal can be life-threatening to an infant or young child (5). Feeding infants: A guide for use in the child nutrition which are easier to digest and less allergenic. Children between twelve and soy-based formula and soy milk should be labeled with the twenty-four months of age, who are not on human milk or infant’s or child’s full name and date and stored properly. Caregiv twenty-four months of age, for whom overweight or obesity ers/teachers should hold infants in the caregiver’s/teacher’s is a concern or who have a family history of obesity, dyslip arms or sitting up on the caregiver’s/teacher’s lap. Bottles idemia, or early cardiovascular disease, the use of reduced should never be propped. The facility should not vider may also recommend reduced fat (2%) milk for some permit an infant to carry a bottle while standing, walking, or children this age. The breastfeeding: American Academy of Pediatrics recommends that cow’s a) Initiate feeding when infant provides cues (rooting, milk not be used during the frst year of life (3-7). Caregivers/teachers can explain A caregiver/teacher should not bottle feed more than one to the children the meaning of the color labels and identify infant at a time. Pediatrics the use of a bottle or cup to modify or pacify a child’s be 122:198-208. American Academy of practices and oral hygiene including proper use of the bottle Pediatrics guide to your child’s nutrition. Neurological development of 5-year-old signifcant short-term and long-term implications for the children receiving a low-saturated fat, low-cholesterol diet since child’s health (7-18). Growth until 3 years of age in a prospective, around with bottle nipples in their mouths. Bottles should randomized trial of a diet with reduced saturated fat and not be allowed in the crib or bed for safety and sanitary cholesterol. It is diffcult for a caregiver/teacher to be aware of and respond to infant feed ing cues when the child is in a crib or bed and when feeding more than one infant at a time. Clinical considerations for an infant need to understand the relationship between bottle feeding oral health care program. Implementing an infants who are bottle feeding whenever possible, even if infant oral care program. Oral health in America: A report of the surgeon general–Executive Caregivers/teachers should offer children fuids from a cup summary. Oral health care a cup is an individual process, which occurs over a wide during pregnancy and early childhood: Practice guidelines. From baby bottle to cup: teachers should use smaller cups and fll halfway or less to Choose training cups carefully, use them temporarily. Brushing up on oral cracks or chips and should help the child to lift and tilt the health: Never too early to start. Dietary determinants of dental of human milk to ensure the child’s receiving adequate caries and dietary recommendations for preschool children. J Public nourishment and to avoid having a large amount of human Health Dent 60:197-206. Nutrition in infancy and human milk can be placed in a clean cup and additional milk childhood. Bottles and infant foods should never be warmed in a feeding on development and incidence of infection in infants. A caregiver/teacher should not hold an infant while Recommendation for preventive pediatric dental care.

At many Superfund sites erectile dysfunction no xplode buy generic viagra sublingual on line, cosmetic changes have been made — rusting barrels have been removed from the surface erectile dysfunction injections videos viagra sublingual 100mg without prescription, and vegetation has reemerged on what were moonscapes 0 years ago impotence sentence examples purchase viagra sublingual on line. Beneath the surface erectile dysfunction and viagra use whats up with college-age males order 100 mg viagra sublingual fast delivery, though, the toxic stews continue to circulate, moldering and spreading, adding chemicals to aquifers, rising to the surface of the soil as the land freezes and thaws, and releasing methane and other volatile gases. The senior federal offcials now responsible for the program provide political spin instead of solutions. They tell us that Superfund does not need the tax money it was intended to have, and that the popular “polluter pays” principle still applies even though the tax on oil and chemical companies has expired. There is no better way to illustrate the bankruptcy of such claims than to get back to basics and look at the nation’s worst sites, the dangers they pose and the paralyzed cleanup response. Specifcally, the report highlights fve sites in each of the top 10 most populous states: California, Texas, New York, Florida, Illinois, Pennsylvania, Ohio, Michigan, New Jersey and Georgia (ranked by size of population). As of the 000 Census (the most recent tabulation of data available at the census tract level), people lived in the census tracts containing one of the 50 profled sites. In 0 of the 0 census tracts (0 percent of tracts), the median household income for 999 (again, the most recent tabulation of data available at the census tract level) was below that for the nation, that is, below $,99. This report also provides the percentage of “minority” (that is, the percentage not classifed as “one race, white”) and “Hispanic” populations around each of the 50 sites. The Census Bureau considered race and Hispanic origin to be “two separate and distinct concepts” for the 000 census (as explained further in Appendix B). Thirteen of the profled sites are located in census tracts where the population is at least 0 percent racial minority or Hispanic, including four sites where the percentage is greater than 70. However, on a site specifc basis, these fndings echo concerns long expressed by scholars and other commentators that hazardous waste sites disproportionately affect minority and low-income populations. Detailed information on the 0 sites and the people who live near them is presented in the state-specifc sections set forth in the next part of this report, beginning on page 9. As shown in Figure 2, the 50 sites profled in this report were assigned scores ranging from. The disposal practices utilized at the 50 sites profled in this report resulted in toxic mixtures of hazardous substances that individually cause everything from cancer to birth defects to brain damage when they seep into drinking water, are emitted into the air, or lace the soil on the sites and in surrounding communities. Most often, these chemicals are invisible, tasteless and odorless, giving little warning when they are present in amounts far above what is safe, for people and for wildlife. As bad as exposure to individual chemicals can be, their effects when they interact with each other have yet to be documented. Equally troubling, Superfund sites represent just one of the many sources of environmental contaminants present in surrounding communities. Once again, our understanding of the cumulative effects of such exposures is preliminary at best. As of April 2006, none of the 50 sites profled in this report had progressed far enough in the cleanup process to be designated “construction complete. Probst & Diane Sherman, Success for Superfund: A New Approach for Keeping Score, at (April 00), available at. AgEncy, Final Rule on National Oil and Hazardous Substances Pollution Contingency Plan, Fed. For more detailed information on the signifcance of the “construction complete” designation, see supra notes 0 and accom panying text. Most of the 50 sites categorized as “proposed” have been in that status for a decade or longer. Region offcials stated that the lack of funding at this site presents “long-term risks to human health and the environment,” noting that without funding to implement a permanent remedy, the contaminated groundwater plume migrating from the site will eventually reach the water well for the City of Jasper, Texas. The sites (and states in which they lie) for which actual funding fell short of requests were: Atlas Tack Corp. Gilt Edge Mine received less funding than requested for both remedial action construction activities (Enclo sure) and long-term response actions (Enclosure). AgEncy, Superfund National Accomplishments Summary Fiscal Year 2005 as of November 22, 2005. For a list of the nine sites that did not receive new construction funding in fscal year 00, please see. Center for American Progress | Center for Progressive Reform these developments have taken a drastic toll on Superfund cleanups. As shown in Figure, the number of construction completions dropped precipitously beginning in 00. Most of the 0 sites are located in heavily populated urban or suburban neighborhoods and contain a toxic soup of harmful chemicals with direct routes of exposure —. The sites were used by manufacturers to dispose of liquid and solid toxic wastes for many decades. Inexplicably, some of the sites that have waited the longest for cleanup are owned by companies that remain viable, even proftable. The runoff of waste polluted the nearby Hackensack River Basin, which is used by local residents for recreation. The Toll of Superfund neglecT Honeywell, has been identifed as a responsible party at the site and has been conducting cleanup activities. In 00, Honeywell was ranked number 75 on the Fortune 500, with profts topping $1. Unlined lagoons were used for disposal of the wastes generated by the production of alcohol-based detergents, saccharin, pesticides, herbicides and dye intermediaries. Final cleanup plans were completed in the early 990s, but negotiations with the companies listed above, among others, slowed implementation until the late 990s, and even then, federal funding was used to construct groundwater treatment facilities. The census tract in which the site is located has a median household income of about $ 8,000. Several of the 0 sites were owned by companies that used extraordinarily toxic chemicals, some of which. Over decades, excess chemicals and metals spilled or dropped onto the bare ground, where they seeped into underground aquifers or were washed by rain into adjacent storm sewers, rivers, or creeks. For example: • the American Creosote Works (Pensacola Pit) site in Escambia County, Florida, was used from 90 98 for wood preserving. Creosote was used until 9 0, when pentachlorophenol became the chemical of choice. Ponds set up to “percolate” these highly toxic liquids overfowed, spilling into Bayou Chico and the Pensacola Bay. The census tract encompassing the site is 8 percent minority, with a median household income of $,000. In 980, the site owner crushed over, 00 drums of trichloroethylene, acid sludges and other toxics, spilling their contents onto the unprotected soil. Center for American Progress | Center for Progressive Reform • the DePue/New Jersey Zinc/Mobil Chemical Company in Bureau County, Illinois,was used by a series of companies to smelt zinc for close to a century, creating waste piles, lagoons and cooling ponds flled with toxic wastes that now threaten a community with a median household income of $ 7,000, as well as the nearby DePue Lake, which houses a fshery, state wildlife refuge and numerous wetlands. Other sites served as dumping grounds for multiple companies, many of which have changed their names, metamorphosing into other businesses or simply disappearing. It served as a hazardous waste disposal facility from 9 97, accepting over million gallons of waste from metal refnishing, electroplating and pesticide manufacturing companies. Rainfall caused the ponds to overfow, sending streams of heavily polluted water into nearby neighborhoods. The population of the census tract around the site is percent minority and has a median household income of $,000. Clearview was covered and re-vegetated in 97, and the Philadelphia Redevelopment Authority constructed hundreds of homes on its eastern and southern borders. The census tract in which the site is located is percent minority, with a median household income of $,000. The Toll of Superfund neglecT At several of the 50 sites profled in this report, hundreds of acres of ordinary household garbage served as the foundation for disposal of millions of gallons of liquid industrial waste. At the time, engineers theorized that the garbage would serve as a sponge, soaking up the corrosive liquid and holding it in place. Far from solving the problem of what to do with these heavily contaminated liquids, the garbage, which covered dozens — even hundreds — of acres, just spread it around. For example: • In Montgomery County, Ohio, the 0 -acre North Sanitary Landfll sits atop an aquifer used for drinking water, which is composed of highly transmissive sands and gravel.

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Epididymitis Epididymitis is an infection of the epididymis erectile dysfunction treatment drugs viagra sublingual 100 mg lowest price, which usually spreads from an infected urethra erectile dysfunction treatment in islamabad buy 100 mg viagra sublingual with visa, bladder erectile dysfunction treatment in lucknow generic 100mg viagra sublingual visa, or prostate erectile dysfunction essential oils buy viagra sublingual overnight. In pre pubertal males, older men, and homosexual men, the pre dominant causal organism is Escherichia coli, although in older men, the condition may also be a result of urinary obstruc tion. Clinical Manifestations • Often slowly develops over 1 to 2 days, beginning with a low-grade fever, chills, and heaviness in the affected testi cle. Epididymitis 289 • Urinary frequency, urgency, or dysuria, and testicular pain aggravated by bowel movement. Nursing Management •Place patient on bed rest with scrotum elevated with a scrotal bridge or folded towel to prevent traction on sper matic cord, to improve venous drainage, and to relieve pain. There may be associated loss of consciousness, excess movement, or loss of muscle tone or movement and disturbances of behavior, E mood, sensation, and perception. The basic problem is an electrical disturbance (dysrhythmia) in the nerve cells in one section of the brain, causing them to emit abnormal, recur ring, uncontrolled electrical discharges. The characteristic epileptic seizure is a manifestation of this excessive neuronal discharge. Epilepsies often follow many medical disorders, traumas, and drug or alcohol intoxication. They are also associated with brain tumors, abscesses, and congenital malformations. Epilepsy affects an estimated 3% of people during their lifetime, and most forms of epilepsy occur in childhood. Epilepsy is not synonymous with mental retardation or illness; it is not associated with intellectual level. Clinical Manifestations Seizures range from simple staring episodes to prolonged con vulsive movements with loss of consciousness. Seizures are classied as partial, generalized, and unclassied according to the area of brain involved. Aura, a premonitory or warning sensation, may occur before a seizure (eg, seeing a ashing light, hearing a sound). Simple Partial Seizures Only a nger or hand may shake; the mouth may jerk uncon trollably; the patient may talk unintelligibly, may be dizzy, or may experience unusual or unpleasant sights, sounds, odors, or taste—all without loss of consciousness. Complex Partial Seizures the patient remains motionless or moves automatically but inappropriately for time and place; may experience excessive emotions of fear, anger, elation, or irritability; and does not remember episode when it is over. Epilepsies 291 Generalized Seizures (Grand Mal Seizures) Generalized seizures involve both hemispheres of the brain. There is intense rigidity of the entire body, followed by alter nations of muscle relaxation and contraction (generalized tonic–clonic contraction). Postictal State After the seizure, patients are often confused and hard to arouse and may sleep for hours. Assessment and Diagnostic Methods • Developmental history and physical and neurologic exami nations are done to determine the type, frequency, and severity of seizures. Medical Management the management of epilepsy and status epilepticus is planned according to immediate and long-range needs and is tailored to meet the patient’s needs because some cases arise from brain damage and others are due to altered brain chemistry. The goals of treatment are to stop the seizures as quickly as possi ble, to ensure adequate cerebral oxygenation, and to maintain a seizure-free state. General anesthe E sia with a short-acting barbiturate may be used if initial treatment is unsuccessful. Surgical Management • Surgery is indicated when epilepsy results from intracranial tumors, abscesses, cysts, or vascular anomalies. Ask about factors or events that precipitate the seizures; document alcohol intake. The condition is a medical emergency that is characterized by continuous E clinical or electrical seizures lasting at least 30 minutes. Repeated episodes of cerebral anoxia and edema may lead to irreversible and fatal brain damage. Common fac tors that precipitate status epilepticus include withdrawal of antiseizure medication, fever, and concurrent infection. Nursing Interventions General Care and Injury Prevention • Perform periodic physical examinations and laboratory tests for patients taking medications known to have toxic hematopoietic, genitourinary, or hepatic effects. Reducing Fear of Seizures • Reduce fear that a seizure may occur unexpectedly by encouraging compliance with prescribed treatment. E • Emphasize that prescribed antiepileptic medication must be taken on a continuing basis and is not habit forming. Improving Coping Mechanisms • Understand that epilepsy imposes feelings of stigmatization, alienation, depression, and uncertainty. Epilepsies 295 • Provide specic guidelines to assess and report signs and symptoms of medication overdose. E • Encourage realistic attitude toward the disease; provide facts concerning epilepsy. Evaluation Expected Patient Outcomes • Sustains no injuries from seizure activity • Indicates a decrease in fear • Displays effective individual coping • Exhibits knowledge and understanding of epilepsy • Experiences no complications of seizures (injury) or com plications of status epilepticus For more information, see Chapter 61 in Smeltzer, S. Risk factors include infections, low humidity, nasal E inhalation of illicit drugs, trauma (including vigorous nose blowing and nose picking), arteriosclerosis, hypertension, nasal tumors, thrombocytopenia, aspirin use, liver disease, and hemorrhagic syndromes. Medical Management A nasal speculum, penlight, or headlight may be used to iden tify the site of bleeding in the nasal cavity. The patient sits upright with the head tilted forward to prevent swallowing and aspiration of blood and is directed to pinch the soft outer portion of the nose against the midline septum for 5 or 10 minutes continuously. Application of anesthetics and nasal decongestants (phenyle phrine, one or two sprays) to act as vasoconstrictors may be necessary. Visible bleeding sites may be cauterized with silver nitrate or electrocautery (high-frequency electrical current). If the origin of the bleeding cannot be identied, the nose may be packed with gauze impregnated with petrolatum jelly or antibiotic ointment. The packing may remain in place for 48 hours or up to 5 or 6 days if necessary to control bleeding. Nursing Management • Monitor vital signs, airway, and breathing, and assist in con trol of bleeding. Esophageal Varices, Bleeding 297 • Teach patient to provide self-care by reviewing ways to pre vent epistaxis: avoid forceful nose blowing, straining, high altitudes, and nasal trauma (including nose picking). Esophageal Varices, Bleeding Bleeding or hemorrhage from esophageal varices is one of the major causes of death in patients with cirrhosis. Esophageal varices are dilated tortuous veins usually found in the submu cosa of the lower esophagus; they may develop higher in the esophagus or extend into the stomach. Risk factors for hemor rhage include muscular strain from heavy lifting; straining at stool; sneezing, coughing, or vomiting; esophagitis or irritation of vessels (rough food or irritating uids); reux of stomach contents (especially alcohol); and salicylates or any drug that erodes the esophageal mucosa. Clinical Manifestations • Hematemesis, melena, or general deterioration in mental or physical status; often a history of alcohol abuse. Monitor carefully to detect early signs of cardiac dysrhythmias, perforation, and hemorrhage. Do not allow the patient to drink uids after the examination until the gag reex returns. Offer lozenges and gargles to relieve throat discomfort, but withhold any oral intake if patient is actively bleeding. Medical Management • Aggressive medical care includes evaluation of extent of bleeding and continuous monitoring of vital signs when hematemesis and melena are present. Nonsurgical treatment is preferred because of the high mor tality associated with emergency surgery to control bleeding from esophageal varices and because of the poor physical con dition of most of these patients. Nursing Management Provide postoperative care similar to that for any thoracic or abdominal operation. See “Preoperative and Postoperative Nursing Management” for additional information. Provide emotional support and pertinent explanations regarding medical and nursing interventions. Exfoliative Dermatitis Exfoliative dermatitis is a serious condition characterized by pro gressive inammation in which erythema and scaling occur. This condition starts acutely as either a patchy or a generalized ery thematous eruption.

These disorders are characterized by megalo­ blastic anaemia erectile dysfunction drugs medications discount viagra sublingual 100 mg otc, neurological involvement erectile dysfunction funny images purchase genuine viagra sublingual on line, stunted Inflammatory bowel diseases erectile dysfunction doctor denver purchase viagra sublingual 100 mg without prescription, infection and drugs erectile dysfunction protocol amazon purchase 100mg viagra sublingual free shipping. Two parasitic infestations prod­ ketoacidosis, hyperammonaemia and hyperglycaemia. Tropical fested by megaloblastic anaemia and encephalopathy sprue results in malabsorption through intestinal villous during the first few months of life. Cholestyramine (a bile acid resin used Complications of B12 deficiency to treat hypercholesterolaemia) can chelate intrinsic Cellular and molecular consequences. The common factor, whereas colchicine (used for acute gout) and consequence of B12 deficiency and genetic disorders several antibiotics (including the anti­tuberculosis drug affecting B12 metabolism is a cellular deficit in one or para­aminosalicylic acid) can act as inhibitors of intrin­ both of the coenzyme forms of B12 (that is, adenosyl­B12 sic factor–B12 endocytosis. At the molecular level, B12 defi­ of use of these drugs is usually insufficient to result in ciency leads to an impaired methylation and impaired clinical B12 deficiency, in contrast to the long­term use metabolism of methylmalonate, which is derived from of drugs such as proton pump inhibitors, histamine H2 the catabolism of certain amino acids and fatty acids receptor antagonists and metformin, as noted above1,5. Although maternal B12 levels tend to increase postpartum, the level of 85,86 factor in cell and animal models. These changes are increase depends on prepregnancy stores, B12 intake (diet and supplements) and consistent with an influence of B12 deficiency on mye­ depletion of the stores during pregnancy. Reported B12 concentrations in human milk 41,179 lin homeostasis and on the amyloid and tau pathways of vary substantially from 150 to 700 pmol per litre. American women are reported to be 300 pmol per litre to >600 pmol per litre, whereas the levels in India and Guatemala are very low (<100 pmol per litre)146,178 or even undetectable in those with very low dietary B12 intake. The long tracts of white matter of B12 and lower levels of homocysteine and methylmalonic acid) is reported in in the posterior and lateral columns of the spinal cord formulafed than in breastfed infants40,41,44. Homocysteine accumulation can B12 deficiency can precede the appearance of haemato­ induce cellular stress, apoptosis and homocysteinylation logical changes and may even occur in the absence of any of functional proteins in the blood and tissues (the for­ haematological complications6. Adenosyl­B12 deficiency leads to an dynamic and vulnerable period of brain development. The causes of the neurological complications remain As with folate deficiency90, maternal low B12 status to be determined. Although there is little clarity on ciency through the formation of odd chain and methyl­ the consequences of subclinical low B12 status in adults, branched chain fatty acids49, but evidence to support this there is evidence that, if allowed to persist, it may increase theory is scant. In addition, the neurological modifiable cause of increased plasma levels of homocys­ complications might be due to inflammation80,81, oxid­ teine in a folic­acid­fortified population residing in a high­ ative stress82 and microvascular disease associated with income country93. S­adenosylmethionine administration reverses these serum levels of B12 and increased serum levels of folate effects and improves spatial memory performance84. This predominantly affects erythroid precursors, giving rise Haematological manifestations. Following intake, it is released from its food carrier proteins by proteolysis in the acidic environment of the stomach, where it binds to haptocorrin. Haptocorrin is produced by the salivary glands and58 protects B12 from acid degradation. Degradation of haptocorrin and the pH change in the duodenum favour B12 binding to gastric intrinsic factor, which is produced by gastric parietal cells. The intrinsic factor–B12 complex binds to the cubam receptor (consisting of cubilin and amnionless2,65,66). This receptor mediates the uptake of the intrinsic factor–B12 complex in the enterocytes of the distal ileum via receptormediated endocytosis. The majority of B12 is stored in the liver; some B12 is excreted in bile and undergoes enterohepatic circulation167,206. Several inherited disorders — designated CblA to CblJ — are associated with mutations in genes encoding proteins involved in intracellular B12 metabolism. Two groups of patients should be consid­ Diagnosis ered for diagnostic testing for B12 deficiency. The first the clinical manifestations of B12 deficiency are varied group comprises those with clinical evidence of B12 and may mimic or are mimicked by various other diseases. In such patients, laboratory tests may anaemia can closely mimic haemolytic anaemia, throm­ help to confirm the diagnosis, but a firm clinical sus­ botic thrombocytopenic purpura and myelodysplastic picion of B12 deficiency warrants immediate treatment syndromes100–103. Empirically, treatment with high­dose B12 while awaiting However, this approach does have its limitations. Autoimmune gastritis and type A chronic atrophicNature Reviews | Disease Primers gastritis can develop in genetically predisposed individuals. Environmental risk factors (such as Helicobacter pylori infection) might also have a role. Chronic atrophic gastritis also represents a risk+ + factor for gastric cancer arising from polypeptideexpressing intestinal metaplasia, as well as enterochromaffinlike cell hyperplasia arising from gastrin hypersecretion by antral G cells predisposing to gastric carcinoid. Pernicious anaemia arises from intrinsic factor deficiency as a result of loss of intrinsic factorproducing gastric parietal cells and the presence of intrinsic factor autoantibodies. In general, Measurement of holotranscobalamin is gradually being if unequivocal or profound B12 deficiency is present, incorporated into the clinical laboratory, but so far, the it is important that it be diagnosed and treated as swiftly biomarker has proved only marginally better than total as possible. Assay sensitive single marker for B12 deficiency, and is often characteristics and confounding factors are summarized used as the ‘gold standard’ for defining B12 status115,116. The major drawbacks are availability and cost of the Serum B12 level is usually the first­line test. A major advantage is that the analyte is very well eral, a value well below the lower limit of the reference standardized, which allows for a uniform interval of ref­ interval is indicative of probable B12 deficiency, whereas erence of 0. In daily prac­ encodes a protein involved in valine catabolism, was tice, the same reference interval is used across age and found to contain a single­nucleotide polymorphism sex, even though the reference interval broadens with (rs291466) that was the most common genetic driver age108. The is widespread in populations (with a minor allele fre­ level of B12 is influenced by the concentration of the quency of 0. Several intervention studies have focused on the effect of correcting hyper­ homocysteinaemia with B12 supplementation. Some, but not all, studies have demonstrated improvements in disease state95,131–136. In one study, supplementation with homocysteine­lowering vitamins that included B12 was effective in reducing the rate of brain atrophy among patients with increased levels of homocysteine at baseline94,96. As stated above, neutrophil with several larger than normal oval erythrocytes present. Typically, infants present with pancyto­ immaturelooking nuclear chromatin and large ‘giant’ granulocytic band form with horseshoeshaped nucleus. Nuclear maturation is retarded in both the erythroid and penia and failure to thrive. Recently, this approach has been further improved by the development of an Determining the cause of B12 deficiency. This of optimal patient management, establishing a cause of newly introduced B12 index is termed cB12 (combined B12 deficiency is highly desirable. The advantage of cB12 is that step is to determine whether the cause is low intake or it is independent of local reference intervals and can be malabsorption, and, if the latter, whether the defect is adjusted to correct for folate status and age. Over the past two decades, use shows a stronger association with haemoglobin con­ of the gold­standard test for assessing B12 absorptive centrations, cognitive function and peripheral nerve capacity — known as the Schilling test — has dwindled conductivity than single markers. At this time, the to essentially zero owing to the lack of availability of prospective clinical usefulness of the index remains to radiolabelled B12 that is required for the test and high be confirmed. Haematological symptoms occur B12 absorption, but this has not yet been developed into in <50% of individuals, and, even when present, macro­ a clinical test140. To diagnose classic perni­ or the use of medications that have no bearing on B12 cious anaemia141, the detection of autoantibodies against status122,123. Deficiency of may be seen also in patients without pernicious anae­ B12 is emerging as a public health concern in many mia143. The mia have atrophic gastritis; when atrophic gastritis is strategies for prevention of B12 deficiency and its pub­ found, other non­immune causes of atrophic gastritis lic health significance may be discussed in a life­course should be excluded. Maternal may prove very valuable for confirming the presence of B12 status during pregnancy and cord blood B12 con­ B12 deficiency and also for adjusting treatment. Importantly, this transgenerational cycle differential diagnosis, and suitable tests, either through becomes self­perpetuating if the fetus is female. This complementation phenotyping or genetic analysis, suggests that improving the nutrition of young girls has should be carried out69–71,75. Maternal B12 status is negatively affected by a combination of diets poor in animal­sourced foods, high fertility rates and n short inter­pregnancy intervals, and further aggrav­ ated by sociocultural factors such as early marriage with adolescent pregnancies, as well as dietary taboos during a pregnancy and lactation. Oral supplementation of urban Indian women with B12 (50 g daily) throughout pregnancy and early lac­ tation significantly increased the B12 status of mothers Biology • Genetics (median: 184 versus 105 pmol per litre; P< 0. Supplementation Maternal inuences improved median breast milk B12 concentration 6 weeks including placental post­partum (136 versus 87 pmol per litre; P< 0. In Bangladesh, maternal supplementation with 250 g of B12 daily dur­ ing most of the pregnancy and 3 months of lactation resulted in improved maternal and infant status, sub­ stantially increased B12 in colostrum and breast milk, and improved influenza H1N1 vaccine­specific response in the mothers147.