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PATHOLOGY 2B PANCREAS ROBERTO D. PADUA JR.,MD,DPSP DEPARTMENT OF PATHOLOGY FATIMA COLLEGE OF MEDICINE
Organ Considerations Greek pankreas means “all flesh” Endocrine and exocrine functions 90 grams in men; 85 grams in women Has 3 parts = head, body, and tail Duct of Wirsung = main pancreatic duct that drains into the duodenum at the papilla of Vater
Duct of Santorini = accessory pancreatic duct that drains into the duodenum through a separate minor papilla
Organ Considerations Embryologically arises from the fusion of dorsal and ventral outpouchings of the foregut Constitutes 80-85% of the pancreas Produce digestive enzymes Composed of islets of Langerhans that constitutes only 1-2% of the pancreas
Secretes insulin, glucagon, and somatostatin
Normal pancreatic anatomy
Congenital Anomalies Total absence of the pancreas Rare; associated with widespread severe malformation
Homozygous mutations in the IPF1 gene on chromosome 13q12.1
Congenital Anomalies Most common congenital anomaly Failure of the fetal duct systems of the dorsal and ventral pancreatic primordia to fuse
Predisposes to development of chronic pancreatitis
Congenital Anomalies Ventral primordium of the pancreas fails to rotate properly Congenital abnormalities of the GIT can be seen Down syndrome is a predisposing condition Encirclement of the duodenum by pancreatic parenchyma constriction of the duodenal lumen Contains large number of PP cells in its many irregularly shaped islets
Presents with duodenal obstruction
Congenital Anomalies Most common in the duodenum (2 nd portion) Seen in the stomach, jejunum, ileum, Meckel’s diverticulum, gastric and intestinal diverticula, GB and bile ducts, large bowel, spleen, omentum, abdominal wall Grossly, resembles normal pancreas firm, yellow, lobulated nodules measuring up to 4 cm, sharply circumscribed from the surrounding tissues Central umbilication is present corresponding to the central duct that opens into the lumen (important diagnostic sign)
Microscopically, acinar and ductal tissues are always present; islet tissue is found only in 1/3 of cases
Acute Pancreatitis Group of reversible lesions characterized by inflammation of the pancreas ranging in severity from edema and fat necrosis to parenchymal necrosis with severe hemorrhage Incidence rate : 10-20 cases/100,000 (Western) Approximately 80% of cases = biliary tract disease or alcoholism Gallstones present in 35-60% of cases of acute pancreatits Severe alcoholoc intake = 65% in the US
Idiopathic = 10-20% of cases
Acute Pancreatitis Cationic Trypsinogen (PRSS1) > point mutation with G to A transitions resulting in an arginine (R) to histidine (H) substitution ( called R122H)
> affects a site on the cationic trypsinogen molecule essential for the cleavage (inactivation) of trypsin by trypsin itself resistant inactivation abnormally active trypsin activates other digestive proenzymes pancreatitis
Acute Pancreatitis Cationic Trypsinogen (PRSS1) > hereditary pancreatitis > autosomal dominant disease with > recurrent attacks of severe
pancreatitis usually beginning in
Acute Pancreatitis 2. Serine Protease Inhibitor, Kazal Type 1 (SPINK1) > the gene codes for a pancreatic trypsin inhibitor
> mutations in the SPINK1 gene pancreatitis
Acute Pancreatitis Gross changes vary from a swollen and edematous well-preserved organ to a hemorrhagic and necrotic mass of tissue Pancreatic substance exhibits areas of red-black hemorrhage interspersed with foci of yellow-white, chalky fat necrosis
Foci of fat necrosis may also be found in the extrapancreatic fat depots, (omentum, mesentery, subcutis)
Acute Pancreatitis Peritoneal cavity contains serous, slightly turbid, brown-tinged fluid in which globules of fat can be identified
Extensive parenchymal necrosis accompanied by diffuse hemorrhage within the substance of the gland
Acute Pancreatitis Ranges from trivial inflammation and edema to severe extensive necrosis and hemorrhage Microvascular leakage causing edema Necrosis of fat by lipolytic enzymes An acute inflammatory reaction Proteolytic destruction of pancreatic parenchyma
Destruction of blood vessels with subsequent interstitial hemorrhage
Acute Pancreatitis Acute interstitial pancreatitis Morphologic changes limited to interstitial edema and focal areas of fat necrosis in the pancreatic substance and peripancreatic fat Acute necrotizing pancreatitis Pancreatic tissue necrosis affects acinar and ductal tissues as well as the islets of Langerhans
Hemorrhage results from damage to the vasculature
Earlier changes are represented by acinar cell homogenization, ductal dilatation with epithelial degeneration, diffuse interstitial edema, leukocytic infiltration, and fibroblastic reaction extensive necrosis and hemorrhage of pancreatic tissue
Acute Pancreatitis Anatomic changes strongly suggest autodigestion of the pancreatic substance by inappropriately activated pancreatic enzymes
Activation of trypsin is an important triggering event in acute pancreatitis
Trypsin Trypsinogen Activate other proenzymes Phospholipase Proelastase Disintegration of fat cells Damage elastic fibers of b.v. Acute Pancreatitis Prekallikrein Kallikrein Kinin system Hageman factor Clotting system Complement system Inflammation Small vessel thromboses
Acute Pancreatitis The manner by which alcohol causes pancreatitis is unknown Transient increases in pancreatic exocrine secretion Contraction of the Sphincter of Oddi Direct toxic effects on acinar cells Many authorities think that most cases of alcoholic pancreatitis are sudden exacerbations of chronic pancreatitis, presenting as apparent de novo acute pancreatitis
Chronic alcohol ingestion causes secretion of protein-rich pancreatic fluid deposition of inspissated protein plugs and obstruction of small pancreatic ducts
Acute Pancreatitis Cardinal manifestation = abdominal pain Pain is constant and intense and is often referred to the upper back Full-blown acute pancreatitis is a medical emergency of the first magnitude Symptoms are due to release of toxic enzymes, cytokines, and other mediators with explosive activation of the systemic inflammatory response leukocytosis, hemolysis, DIC, fluid sequestration, ARDS, and diffuse fat necrosis
Peripheral vascular collapse and shock with acute renal tubular necrosis may occur
Acute Pancreatitis Pancreatic necrotic foci can undergo secondary infection infected pancreatic necrosis Currently regarded as the most common, most severe, and most lethal of the infectious complications Occurs in 40-60% of patients with acute necrotizing pancreatitis Usually involves Gram-negative organisms from the alimentary tract
can evolve into a chronic form
Acute Pancreatitis Serum amylase level elevation in the first 24 hours Elevation of serum lipase within 72 to 96 hours Glycosuria occurs in 10% of cases Elevated serum C-reactive protein is a reliable marker for the presence of pancreatic necrosis Hypocalcemia – a poor prognostic sign
results from precipitation of calcium soaps in the fat necrosis
Acute Pancreatitis “ Resting” the pancreas by total restriction of food and fluids and by supportive therapy Medical (4-6 hrs) deteriorate emergency laparotomy Others : emergency endoscopic retrograde cholangiopancreatography with or w/o endoscopic papillotomy
Presence of an upper abdominal mass suspected of being pseudocyst and persistent rising jaundice are indications for surgical intervention
SEQUELAE OF ACUTE PANCREATITIS
Chronic Pancreatitis Characterized by inflammation of the pancreas with destruction of exocrine parenchyma, fibrosis, and, in the late stages, the destruction of endocrine parenchyma
Irreversible impairment of pancreatic function
Chronic Pancreatitis Long-standing obstruction of the pancreatic duct Attributed to malnutrition Mutations in the PRSS1 and SPINK1 genes Idiopathic chronic pancreatitis
Mutations in cystic fibrosis transmembrane conductance regulator ( CFTR ) gene
Chronic Pancreatitis Etiologic factors (Rosai and Ackerman, 9 th ed) Obstruction of the ductal system by carcinoma or stones Chronic alcoholism most common
Secondary extension of sclerosing cholangitis
Chronic Pancreatitis Pathogenesis – Hypotheses Ductal obstruction by concretions Alcohol increase protein concentrations in the pancreatic juice ductal plugs obstruct the pancreatic ducts
Toxins including alcohol and its metabolites can exert toxic effect on acinar cells accumulation of lipids in acinar cells acinar cell loss parenchymal fibrosis
Chronic Pancreatitis Pathogenesis – Hypotheses Alcohol-induced oxidative stress generate free radicals in acinar cells membrane lipid oxidation and activation of transcription factors (AP1 and NF κβ ) expression of chemokines attracts mononuclear cells
Promotes fusion of lysosomes and zymogen granules, acinar cell necrosis, inflammation, and fibrosis
Chronic Pancreatitis Pathogenesis – Hypotheses Acute pancreatitis perilobular fibrosis, duct distortion, and altered pancreatic secretions over time and with multiple episodes loss of pancreatic parenchyma and fibrosis
*** Chemokines have been identified in chronic pancreatitis (IL-8, MCP-1) plus TGF- β , PDGF induce the activation and proliferation of periacinar myofibroblasts (pancreatic stellate cells) deposition of collagen fibrosis
Visible calcified concretions
Chronic Pancreatitis Reduced number and size of acini with relative sparing of the islets of Langerhans Variable dilation of the pancreatic ducts Chronic inflammatory infiltrate around lobules and ducts Interlobular and intralobar ducts are dilated with protein plugs in their lumens Ductal epithelium is atrophied or hyperplastic or may show squamous metaplasia
Ductal concretions may be evident
Chronic Pancreatitis S/Sx varies = recurrent attacks of abdominal pain/back pain May be entirely silent until pancreatic insufficiency or DM develops Attacks are precipitated by alcohol abuse, overeating, or the use of opiates and other drugs that increase the tone of the sphincter of Oddi
Diagnosis requires a high degree of suspicion
Chronic Pancreatitis Attack of abdominal pain mild fever and mild to moderate elevation of serum amylase (absent with destruction of acinar cells) Gallstone-induced obstruction Elevation of alkaline phosphatase CT and UTS – visualize calcification
Weight loss and hypoalbuminemic edema from malabsorption caused by exocrine pancreatic insufficiency
Chronic Pancreatitis Acinar necrosis and acute inflammation are seen more often in patients with persistent pain than in those who are free of pain Pancreatic duct drainage (through pancreacojejunostomy or endoscopic removal of ductal stones) Partial pancreatic resection
Near-total pancreatectomy with or without islet autotransplantation
Chronic Pancreatitis Not an immediately life-threatening condition, long term outlook is poor 20-25 year mortality rate of 50%
Hereditary pancreatitis – 40% lifetime risk of developing pancreatic cancer; unclear for other forms
SEQUELAE OF CHRONIC PANCREATITIS
Pancreatic Transplantation Insulin-resistant diabetes mellitus
At present, pancreatic graft survival rates approach 90% at 1 year
Abscess Most often seen as complications of acute pancreatitis
Characterized by the presence of pus and the microbiologic identification of bacteria in over 90% of cases
Non-Neoplastic Cysts Result from anomalous development of the pancreatic ducts May be associated with polycystic disease and von Hippel-Lindau disease Range from microscopic lesions to 3-5 cm in diameter Lined by a glistening duct type cuboidal epithelium or by a completely attenuated cell layer
enclosed in a thin fibrous capsule filled with clear to turbid mucoid or serous fluid
Non-Neoplastic Cysts Related to pancreatitis, trauma, and rarely, to neoplastic obstruction of large ducts They can become very large, and spread beyond the substance of the pancreas Lack of epithelial lining Wall is thick and irregular
Intraluminal content is cloudy or bloody
Non-Neoplastic Cysts Complications = perforation and hemorrhage (splenic artery) Small pseudocysts located in the body or tail of the pancreas = excision External drainage (preferred for the infected cysts) Contraindicated if the cysts connect with the ductal system Transgastric cystgastrostomy
Cystojenunostomy to a Roux-en-Y loop of jejunum
Cystic Neoplasms Only 5-15% of pancreatic cysts are neoplastic 5% of all pancreatic neoplasms
Can be benign, borderline malignant, or malignant
Cystic Neoplasms Benign cystic neoplasms consists of glycogen-rich low-cuboidal cells surrounding small cysts Contains clear, thin, straw-colored fluid Account for about 25% of all cystic neoplasms of the pancreas Occurs twice in women than in men; 7 th decade of life Non-specific S/Sx like abdominal pain or palpable abdominal mass
Treatment : surgical resection
Cystic Neoplasms Mucinous cystic neoplasms Almost always arise in women Can be benign, borderline malignant, or malignant Arises in the body or tail Present as painless, slow-growing masses Cysts are lined by columnar mucinous epithelium containing thick, tenacious mucin Diagnosis is only done after removal
Treatment is distal pancreatectomy
Cystic Neoplasms Intraductal papillary mucinous neoplasms ( IPMNs ) Produce cysts containing mucin Can be benign, borderline malignant, or malignant Occurs more frequently in men Involve the head of the pancreas more often than the tail Lack the dense “ovarian” stroma
Arise in the main pancreatic ducts
Cystic Neoplasms Solid-pseudopapillary tumor Seen mainly in adolescent girls and young women Large, well-circumscribed masses with solid and cystic areas Cystic areas are filled with hemorrhagic debris and neoplastic cells grow in solid sheets or as papillary projections Can present with abdominal discomfort because of their large size Alteration of the β -catenin/adenomatous polyposis coli genetic pathway
Treatment : surgical resection
Pancreatic Carcinoma 85% of all cases of pancreatic malignancy 4 th most common cause of death from cancer (US) Incidence is increasing, particularly in women Risk factors : B-naphthylamine or benzidine exposure, cigarette smoking, diet rich in fats, chronic pancreatitis, and DM 10% show familial aggregation consistent with genetic susceptibility
Most patients are elderly (60-80 y/o), with slight male preponderance (1.6:1 ratio)
Pancreatic Carcinoma Diagnosis is made when tumor becomes relatively large (about 5 cm) and has extended beyond the pancreas (85% of cases) Carcinomas of the body and tail grow insidiously and often have already metastasized at the time of diagnosis Associated with peripheral venous thrombi in 25% of patients Diagnosis : CT-scan, MRI, celiac angiography, UTZ, ERCP, seleno-methionine scan, duodenal aspirate, serum test
Tumor markers : SPan1 and CA19-9 antigen
Pancreatic Carcinoma Precursors to Pancreatic Cancer Lesions are called “pancreatic intraepithelial neoplasias” (PaINs) Supported by the following observations The distribution parallels that of invasive cancer Often found in pancreatic parenchyma adjacent to infiltrating carcinomas Patients with PaINs later developed an invasive pancreatic cancer The genetic alterations identified in PaINs are similar to those present in invasive cancers
The epithelial cells in PaINs show dramatic telomere shortening predispose these lesions to accumulate progressive chromosomal abnormalities and to develop invasive carcinoma
Pancreatic Carcinoma K-RAS gene is the most commonly altered oncogene
Activated by point mutation impair GTPase activity of K-ras gene active protein Ras activates several intracellular transduction pathways activation of transcription factors fos and jun
Pancreatic Carcinoma p16 gene (chromosome 9p) is the most frequently inactivated tumor suppressor gene in pancreatic cancer Inactivated in 95% of cases p16 plays a critical role in the control of the cell cycle Inactivation of the p53 tumor suppressor gene (chromosome 17p) seen in 50-70% of pancreatic Ca
Gene product is nuclear DNA-binding protein that acts both as a cell cycle checkpoint and as inducer of cell death (apoptosis)
Pancreatic Carcinoma Tumor suppressor gene (chromosome 18q) is inactivated in 55% of pancreatic cancers Also known as DPC4 , codes for protein that plays an important role in signal transduction from the TGF- β family of cell surface receptors
Normal function of this gene is to suppress growth and promote apoptosis
Inactivated tumor suppressor genes
Pancreatic Carcinoma Methylation abnormalities Hypermethylation of the promoter of a number of suppressor genes is associated with transcriptional silencing of the genes Identified a number of genes that are highly overexpressed in pancreatic cancers
Potential targets for therapeutics and may form the basis for future screening tests
Pancreatic Carcinoma Location : head of the pancreas (60%), body (15%) or tail (5%) Multiple tumors are found in 20% of cases Majority are ductal adenocarcinomas Poorly delineated and firm, with a yellow cut-surface May undergo massive cystic degeneration Duodenal wall is invaded by direct extension in tumors involving the head of the pancreas causing obstruction of the distal CBD
Involved pancreatic ducts are dilated and plugged with necrotic tumor
A cross-section through the head of the pancreas and adjacent CBD showing both an ill-defined mass in the pancreatic substance and the green discoloration of the duct resulting from total obstruction to bile flow.
Pancreatic Carcinoma Graded as well-differentiated, moderately differentiated, and poorly differentiated LPO = glands are well formed, have a large lumen, and are lined by one or few layers of cylindrical or cuboidal epithelium Their overall LPO appearanace may be be particularly suggestive of carcinoma except for the irregularities in the shape and distribution of the glands and the peculiar concentric desmoplastic stroma that surrounds them
Perineural invasion – 90% of cases
Poorly formed glands are present in densely fibrotic stroma within the pancreatic substance with presence of some inflammatory cells.
Pancreatic Carcinoma Histochemical and Immunohistochemical features Positive for mucin stains Consistent reactivity for keratins and EMA Glycoprotein MUC1 is expressed in over 60% of conventional invasive ductal carcinoma
Others : CEA, CA19-9, B72.3, DUPAN-2, YPan-1, SPan-1, Tn and sialosyl-Tn antigens, DF3
Pancreatic Carcinoma Tends to metastasize to multiple LN located around the organ Most commonly involved the LN around the common hepatic artery, hepatoduodenal ligament, posterior pancreaticoduodenal, around the superior mesenteric artery, para-aortic, and anterior pancreatico-duodenal
Microscopic metastasis were found in T1 and T2 lesions
Pancreatic Carcinoma Most common sites of distant metastasis are liver, peritoneum, lung, adrenal, bone, distant LN groups, skin, and CNS
Supraclavicular LN metastasis is sometimes the first manifestation of pancreatic carcinoma
Pancreatic Carcinoma Overall 5-year survival rate = 4% or less with over 90% of patients dying within 1 year of diagnosis Mean survival of 3 months for untreated patients
Even if the tumor is confined at the pancreas at the time of diagnosis, the 5-year survival rate does not exceed 15%
Pancreatic Carcinoma Tumor stage – most important prognostic indicator Microscopic grade – well-differentiated tumor have longer survival rate Tumor size - <4.5 cm have better chance of curative operation
Blood vessel invasion and retroperitoneal margin of resection – decreased survival
TGF-B1 expression – associated with well-differentiated tumor
American Joint Committee for Cancer Staging for Carcinoma of the Pancreas TNM classification criteria T1 No direct extension of the primary beyond the pancreas T2 Limited direct extension to the duodenum, bile duct, or stomach T3 Advanced direct extension incompatible with surgical resection TX Direct extension not assessed N0 Regional nodes not involved N1 Regional nodes involved NX Regional LN not assessed
American Joint Committee for Cancer Staging for Carcinoma of the Pancreas TNM classification criteria M0 No distant metastasis M1 Distant metastasis present MX Distant metastasis not assessed TNM Stages Stage I T1-2, N0, M0 Stage II T3, N0, M0 Stage III T1-T3, N1, M0 Stage IV Any T or N, M1
Pancreatoblastoma Most common form of pancreatic neoplasia in childhood, but can also occur in adults Reported in patients with Beckwith-Wiedemann syndrome and familial adenomatous polyposis of the colon Bimodal age distribution = mean of 2.4 and 33 years
Mean tumor size is 10 cm and partial encapsulation is the rule
Pancreatoblastoma Very cellular tumors, made up of uniform epithelial cells arranged in solid sheets and nests, admixed with well-formed acinar structures and occasional ductular formations “ Squamoid corpuscles” are a constant and characteristic finding Positivity for pancreatic enzymes, endocrine markers, and CEA
Alpha-fetoprotein may be produced by the tumor
Treatment : Surgical resection
ENDOCRINE PANCREAS ROBERTO D. PADUA JR.,MD,DPSP DEPARTMENT OF PATHOLOGY FATIMA COLLEGE OF MEDICINE
Endocrine Pancreas Consists of about 1 million microscopic clusters of cells, the islets of Langerhans Aggregate weight of 1-1.5 grams Β eta cells – 68%; insulin Alpha cells – 20%; glucagon Delta cells – 10%; somatostatin
PP cells – 2%; pancreatic polypeptide that exerts its effect on the GIT stimulation of secretion of gastric and intestinal enzymes and inhibition of intestinal motility
Endocrine Pancreas D1 cells – elaborates VIP, a hormone that induces glycogenolysis and hyperglycemia; stimulates gastrointestinal fluid secretion and causes secretory diarrhea
Enterochromaffin cells – synthesize serotonin and are sources of pancreatic tumors that cause the carcinoid syndrome
Diabetes Mellitus A group of metabolic disorder sharing the common underlying feature of hyperglycemia Hyperglycemia results from defects in insulin secretion, insulin action, or both
Causes multi-organ damage affecting the kidneys, eyes, nerves, and blood vesels
Carbohydrate Metabolism Carbohydrates broken down by salivary, gastric & intestinal (pancreatic) enzymes into simple sugars G G G G G
absorbed by the intestines ( α -glucosidase) into the bloodstream
What is glucose? Glucose is an essential nutrient that provides energy for the proper functioning of the body cells. MAN needs glucose to work CAR needs fuel to move FUEL
Blood Glycogenolysis (-) GLUCAGON (+) INSULIN Fed State Pyruvate/Lactate Amino acids Glycerol / FFA Glycogenesis X X *All cells
Blood Glycogenolysis (+) GLUCAGON (-) INSULIN Postabsorptive / Fasting State Pyruvate/Lactate Amino acids Glycerol / FFA Glycogenesis *6-8hrs after a meal First 24-48hrs Preferentially used by brain, & other non-insulin dependent tissues X
Blood Glycogenolysis (+) GLUCAGON EPINEPHRINE CORTISOL GROWTH HORMONE (-) INSULIN Postabsorptive / Fasting State Glycogenesis After 48hrs of fast Lipolysis Proteolysis Ketogenesis Ketones for brain Pyruvate/Lactate Amino acids Glycerol / FFA
Insulin 4 major cell types in the islets of Islets of Langerhans
F (or PP) cell pancreatic polypeptide.
Initially synthesized as preproinsulin
INSULIN BIOSYNTHESIS Enzymatic cleavage produces
“ secreted in equal amounts”
INSULIN BIOSYNTHESIS Less susceptible to hepatic degradation
marker of insulin secretion
INSULIN BIOSYNTHESIS A chain of 21 amino acids B chain of 30 amino acids
chains held together by two disulfide
Classification of Glucose Transport According to Their Tissue Distribution and Functional Regulation Glucose Organ Transporter HK Coupler Classification Brain GLUT 1 HK-I Insulin independent Erythrocyte GLUT 1 HK-I Insulin independent Adipocyte GLUT 4 HK-II Insulin dependent Muscle GLUT 4 HK-II Insulin dependent Liver GLUT 2 HK-IVL Glucose sensor GK -cell GLUT 2 HK-IVB Glucose sensor (Glucokinase) Gut GLUT 3-symporter - Sodium dependent Kidney GLUT 3-symporter - Sodium dependent
INSULIN SECRETION by beta cells GLUT-2 Voltage-gated Ca ++ channel K + ATP Ca ++ III. Increased ATP closes K-channels resulting in membrane depolarization I. blood glucose high, taken up by B cells via GLUT2 II. Metabolism of glucose generates ATP V. Rise in calcium promotes margination, fusion with membrane, and release of insulin & c-peptide cell (-) SUR G Glucose-6-P Kreb’s cycle (glycolysis) ATP production
IV. Membrane depolarization opens Ca-channel with influx of calcium
PHYSIOLOGIC INSULIN SECRETION 7:00am 7:00pm noon midnight 7:00am prandial insulin secretion, (spikes in response to food) Polonsky. N Engl J Med. 1996;334:777-783 Pancreas secretes approximately 40-50 units of insulin per day Breakfast Lunch Breakfast
Continuous basal insulin secretion (unstimulated) 50%
Meal-stimulated Biphasic Insulin Secretion releases preformed insulin - occurs after 10 minutes - continues as long as an hour
release of preformed insulin, newly synthesized insulin
Early Insulin Secretion Helps Control Post-meal Glucose Levels & DM
Immediate Tissue Membrane transport of glucose Muscle, adipose, liver Intermediate Carbohydrate metabolism Glycogen synthesis Muscle, liver Glycogenolysis Muscle, Liver Gluconeogenesis Liver Lipid metabolism Lipogenesis Liver, adipose Lipolysis Adipose Cholesterol synthesis Liver Ketogenesis Liver Protein metabolism Protein synthesis Liver, muscle, adipose INSULIN ACTION
catabolized primarily in the liver and kidney INSULIN CATABOLISM
insulin-specific protease (insulinase)
Cell = Powerplant Keyhole = Insulin Receptor G G G G G G G Key = Insulin Glucose
Keyhole = Insulin Receptor G G G G G Key = Insulin CELL = POWERPLANT
G G G G G CELL = POWERPLANT Energy G G G G G G
DIABETES Greek MELLITUS Latin Sweet as honey To pass water like a siphon
G G G G G Type 1 DM insulin (key) absent G G G G G Type 2 DM defective insulin receptor (keyhole) with insufficient insulin Insufficient production of insulin or the inability of cells to use insulin (insulin resistance). What causes it?
“ Sweet Urine” Diabetes Mellitus group of metabolic disorders characterized by high blood sugar levels Hyperglycemia can lead to spillage of glucose into the urine (> 180 renal threshold)
Diabetes Mellitus Metabolic abnormality involving protein, fat and carbohydrate processing
Leading to multi-organs complications
SYMPTOMS OF DIABETES Polyuria Polydipsia Polyphagia
SYMPTOMS OF DIABETES Poor Wound Healing Weight Loss Weakness and Fatigue Blurring of Vision
SYMPTOMS OF DIABETES Many have no symptoms. They are noted to have high blood sugar on testing.
RISK FACTORS FOR DIABETES Heredity Old Age Obesity Mothers of large babies
Criteria for diagnosis of DM ADA 2004 Note: criteria should be confirmed by repeat testing on a different day.
CRITERIA FOR DIAGNOSIS OF DIABETES MELLITUS “ prediabetics” – risk for developing type 2 DM (40% risk over 5yrs) & CV disease Level of glycemia at which diabetic chronic complications occur American Diabetes Association 8 hr Fasting Blood Sugar 2 hours after 75g glucose (OGTT) NORMAL < 100 mg/dL < 140 mg/dL IMPAIRED FASTING GLYCEMIA (IFG) 100 and < 126 mg/dL --- IMPAIRED GLUCOSE TOLERANCE (IGT) --- 140 and < 200 mg/dL DIABETES MELLITUS 126 mg/dL 200 mg/dL Symptoms of diabetes and Random Blood Sugar of 200 mg/dL
Etiology of DM Insulin action defect (insulin resistance/ receptor defect)
Excess counter-regulatory hormones (glucagon, catecholamines, cortisol, growth hormone)
Etiologic Classification of DM exocrine I. II. III. IV. Based on pathologic process that leads to hyperglycemia
Etiologic Classification of DM Previous terms: juvenile-onset DM, IDDM absolute insulin deficiency due to autoimmune beta cell destruction Triggered by infectious or environmental stimulus Pathology: “insulitis” pancreas infiltrated by lymphocytes Major susceptibility gene: HLA on chrom6 TYPE IA : presence of immunologic markers (islet cell autoAbs, anti-GAD, anti-insulin abs) I. II. III. IV.
TYPE IB : idiopathic, immunologic markers absent
Diabetes Mellitus Type 1 Mechanisms of B-cell dysfunction T lymphocytes react against B-cell antigens and cause cell damage Locally produced cytokines damage β cells
Autoantibodies against islet cells and insulin are also detected in the blood of 70-80% of patients
Etiologic Classification of DM I. II. III. IV. Genetic predisposition Immunologic trigger No DM with DM Beta cell mass (%) 100 50 20 0 Time (years) Overt DM
Etiologic Classification of DM I. II. III. IV. Previous names: NIDDM, adult-onset DM
Visceral Obesity common (contributes to insulin resistance)
Three Pathophysiologic Mechanisms of Type 2 Diabetes Glucose (G) Insulin (I) I I I I I I I G G G G G G G G I G G G I G Fasting hyperglycemia Postprandial hyperglycemia Carbohydrate Impaired insulin secretion Excessive fatty acid release Reduced peripheral glucose Uptake and usage Excess liver glucose output (gluconeogenesis) Resistance to the action of insulin
Natural history of type 2 diabetes: a progressive disease Post-prandial glucose Abnormal glucose tolerance Insulin resistance Increased insulin resistance Fasting glucose Hyperglycemia Insulin secretion Hyperinsulinemia, then -cell failure Adapted from International Diabetes Center (IDC), Minneapolis, Minnesota. Normal IGT Type 2 diabetes
Diabetes Mellitus Type 2 Inability to adapt to the long-term demands of peripheral insulin resistance and increased insulin secretion Loss of normal pulsatile, oscillating pattern of insulin secretion and attenuation of the first phase of insulin secretion triggered by elevation in plasma glucose
Reflected by a decrease in β -cell mass, islet degeneration, and deposition of islet amyloid (amylin)
Etiologic Classification of DM MODY (Maturity-onset diabetes of the young) primary defect in β -cell function that occurs without β -cell loss, affecting either β -cell mass and/or insulin production single gene mutation (monogenic) islet cell transcription factor (HNF)
Lack of islet cell autoantibodies and insulin resistance syndrome
Etiologic Classification of DM Mutation in insulin receptor leading to severe insulin resistance Type A insulin resistance Rabson-Mendenhall syndrome
Defects in proinsulin conversion
Etiologic Classification of DM exocrine >80% of pancreas destroyed
Etiologic Classification of DM Acromegaly (growth hormone) Cushing’s syndrome (cortisol)
Etiologic Classification of DM
Etiologic Classification of DM
Autoimmune beta cell destruction
Etiologic Classification of DM Genetic syndromes associated with diabetes
Etiologic Classification of DM usually reverts to normal 30-60% risk of developing 50g OGCT (glucose challenge test) - measure plasma glucose 1hr after Threshold: ≥ 130-140mg/dL IV.
Dx criteria: ≥95mg/dl fasting
1 . > 45 yrs, if normal, repeat at 3-year intervals 2. Check at a younger age: - have a first-degree relative with diabetes - high-risk ethnic population (e.g., African- American, Hispanic American, Native American, Asian-American, Pacific Islander) - have delivered a baby > 9 lb - have been diagnosed with GDM - hypertensive ( > 140/90) - have HDL < 35 mg/dl and/or triglyceride > 150 mg/dl Recommendations for DM Testing (ADA 2004)
- cardiovascular, cerebrovascular diseases
Glycemic goals 1 American Diabetes Association. Diabetes Care 2004; 27:S15–S35. 2 American Diabetes Association. Diabetes Care 2002; 25:S35–S49. 3 American Association of Clinical Endocrinologists. Endocrine Pract 2002; 8 (Suppl. 1):40–82. 4 European Diabetes Policy Group. Diabet Med 1999; 16:716–730. Fasting/pre-prandial plasma glucose < 140 < 180 Postprandial plasma glucose < 110 90–130 Biochemical index AACE 3 ADA 1,2 mg/dl mmol/l mg/dl mmol/l 5.0–7.2 < 10.0 < 6.5 < 7 HbA 1c (%) < 6.0 < 7.8
HBA1c Excess blood sugar non-enzymatically binds to portion of Hgb (irreversible) A1C levels provide a 2- to 3-month index of glycemic control Assess overall blood glucose control 1. Pickup JC. In: Pickup JC, Williams G, eds. Textbook of Diabetes . 3rd ed. Boston, Mass: Blackwell Science; 2003. 2. Clark N. In: Leahy JL, Cefalu WT, eds. Insulin Therapy . New York, NY: Marcel Dekker, Inc.; 2002. 3. Cefalu WT. In: Leahy JL, Cefalu WT, eds. Insulin Therapy . New York, NY: Marcel Dekker, Inc.; 2002.
Albumin Fructosamine (1-2 weeks)
It cannot be cured. But it can be controlled by keeping blood sugar level within normal range. Diabetes Mellitus
Why do I need to control Diabetes?
COMPLICATIONS OF UNCONTROLLED DIABETES
Morphology of Diabetes Reduction in the number and size of islets Leukocytic infiltration of the islets (insulitis) β -cell degranulation by EM Subtle reduction in islet cell mass – DM 2 Amyloid replacement of islets – DM 2
Islet cell hyperplasia in newborns of diabetic mothers
MACROVASCULAR COMPLICATIONS Diabetics are prone to have high bad cholesterol. When cholesterol is too high, the walls of large blood vessels become narrowed, even clogged. This problem is called accelerated atherosclerosis.
Hallmark of diabetic macrovascular disease
Narrowed and clogged blood vessels decrease blood flow to all parts of your body especially the heart and brain. This can lead to heart attack and stroke. MACROVASCULAR COMPLICATIONS
MI is the most common cause of death in diabetics
Gangrene of the lower extremities result of advanced vascular disease 100X more common in diabetics MACROVASCULAR COMPLICATIONS
vascular lesion associated with hypertension
Longstanding high blood sugar also damages the small blood vessels supplying the eyes (retinopathy), kidneys (nephropathy), and nerves (neuropathy) MICROVASCULAR COMPLICATIONS
Erectile difficulty and impotence may happen due to damage to nerves going to the sexual organ.
Normal retina Diabetic retinopathy Preproliferative Proliferative Vitreous Hemorrhage BLINDNESS
Diabetic Neuropathy Peripheral Neuropathy Autonomic Neuropathy Erectile difficulty Constipation
Diabetic Nephropathy Renal failure is 2 nd only to MI as a cause of death Three lesions encountered renal vascular lesions – arteriosclerosis
pyelonephritis and necrotizing papillitis
Diabetic Nephropathy Capillary basement membrane thickening Occur throughout their entire length Detected by EM within a few years of onset Diffuse mesangial sclerosis Diffuse increase in mesangial matrix and is always associated with basement membrane thickening Seen in most patients with disease of >10years Manifest with nephrotic syndrome proteinuria, hypoalbuminemia, edema
Diabetic Nephropathy Nodular glomerulosclerosis Kimmeltiel-Wilson lesion -- ball-like deposits of a laminated matrix situated in the periphery of the glomerulus PAS positive containing trapped mesangial cells Seen in 15-30% of long-term diabetics
Major cause of morbidity and mortality
Diabetic Nephropathy Renal atherosclerosis and arteriosclerosis
Hyaline arteriosclerosis affects both the afferent and efferent arterioles
POORLY-CONTROLLED DIABETICS are … 2-4 times more prone to HEART DISEASE 25 times more prone to BLINDNESS 90 times more prone to NEUROPATHY 5 times more prone to GANGRENE
17 times more prone to KIDNEY DISEASE
HOW DO I PREVENT COMPLICATIONS?
Checking Your Blood Sugar
Why do I need to check my blood sugar? Checking your blood sugar with a meter helps see how food, physical activity and medicines affect blood sugar level. The readings can help you manage diabetes day by day.
Keep a record of the test results to review with your doctor.
What is a good self-testing blood glucose goal? Your doctor will set the appropriate goal for you. The self-testing blood glucose goals for most people with diabetes are as follows: Premeals 80-120mg/dL At bedtime 100-140mg/dL
Guarding Your Heart
Guarding the Heart Keep blood pressure under 130 / 80 Keep blood sugar controlled Keep cholesterol controlled LDL (bad cholesterol) < 100mg/dL HDL (good cholesterol) > 40 (men) > 50 (women) Exercise. Lose weight if needed.
Take an aspirin once a day.
Guarding Your Kidneys
Guarding the Kidneys Keep blood pressure under 130 / 80 Keep blood sugar well-controlled Avoid dehydration. If there's vomiting or diarrhea, consult your doctor. Do not self-medicate especially with If you have proteinuria, see a dietitian
for individualized meal planning.
Guarding the Kidneys See a doctor for bladder or kidney infections. You may have an infection if you have: pain or burning when you urinate frequent urge to go to the bathroom urine looks cloudy or reddish
back pain or on the side below the ribs
Caring for Your Eyes
PROPER EYE CARE Good blood sugar control.
Visit your eye doctor at least once a year.
Caring for Your SKIN
Use talcum powder in areas where skin touches skin, such as armpits and groin.
Skin care Use an oil-in-water skin cream or lotion. Moisturizing soaps may help.
Don't take bubble baths if your skin is dry.
Skin care Moisturize your skin to prevent chapping, especially in cold or windy weather. See a dermatologist about skin problems you are not able to solve yourself.
Do not scratch dry or itchy skin.
Skin care Wash minor cuts with soap and water. Use an antibiotic cream or ointment if your doctor says it's okay. Cover minor cuts with sterile gauze. See a doctor right away if you get a major cut, burn, or infection.
Do not use Mercurochrome antiseptic, alcohol, or iodine to clean skin because they are too harsh .
Caring for Your FEET
Footcare Wash your feet in lukewarm, NOT HOT , Dry your feet well especially between the toes. Wash your feet everyday
Talcum powder may be used in between the toes.
Check your feet everyday Check for cuts, sores, red spots, swelling, and If you have trouble bending over, a mirror Footcare
may be used or ask a family member to
Keep your skin soft and smooth Footcare Rub a thin coat of lotion or cream over the top and bottom of your feet.
Do not put lotion between your toes.
Trim toenails each weekend and when needed Footcare Trim the toenails straight across and smooth them with an emery board or nail file. Do not cut into the corners or rip off hangnails.
Do not scrape calluses with blades.
Wear shoes and socks at all times Wear shoes that fit well and protect your feet. Footcare Check the insides of the shoes before putting them on. Do not wear tight socks, rubber bands, or garters around your legs.
Do not wear restrictive or ill-fitting shoes.
Protect your feet from hot and cold Wear shoes at the beach or on hot pavement. Footcare If your feet are cold, wear seamless socks at night.
Do not put hot water bottle or heating pad on your feet.
Do not wade in floodwaters without boots Footcare
Put feet up when you are sitting. Wiggle toes for 5 min, 2-3 x a day. Footcare Keep blood flowing to your feet Move ankles up, down and sideways to improve blood flow. DO NOT cross your legs for long periods of time.
DO NOT smoke. Smoking reduces blood flow to your feet.
Caring for Your TEETH
Caring for Your TEETH A film of bacteria, saliva and food particles (dental plaque) constantly forms on the teeth. Bacteria feed on sugars and starches in foods and produce acids that damage teeth enamel.
Caring for Your TEETH High blood sugar gives bacteria more food supply producing more acid, damaging the enamel leading to tooth decay.
Caring for Your TEETH If plaques are not removed with brushing and flossing, it hardens under the gumline into “tartar”. Tartar irritates the gums causing gum inflammation (gingivitis).
Brush your teeth at least twice a day especially after each meal and snack. Use soft-bristled brush. Floss daily . Caring for Your TEETH
See your dentist at least 2x a year. Consult your diabetes doctor prior to any dental extraction. Caring for Your TEETH
LIVING WITH DIABETES EDUCATION DIET EXERCISE MEDICINES
BALANCED DIET Benefits
BALANCED DIET wellnessbread.com Eat more of the foods at the bottom. Eat less of the foods at the top.
BALANCED DIET Eat your meals and snacks at about the same times each day. Do not skip meals or snacks. Take your medicines at about the same times each day. How can I keep my blood glucose at a healthy level? National Diabetes Information Clearinghouse (NIDDK, NIH)
Exercise at about the same times each day.
Eat more of whole grain breads and cereals, vegetables and fruits. Use table salt and sugar in moderation. Eat fewer fried and high-fat foods such as potato chips, french fries or biscuits. Trim off extra fat from pork and beef. Eat chicken without the skin. Healthy Eating National Diabetes Information Clearinghouse (NIDDK, NIH)
Limit alcoholic drinks to one or two a day.
EXERCISE Lowers blood glucose levels Benefits
Promotes healthier heart & circulation
AEROBIC EXERCISES exercise the cardiovascular system
(heart, lungs, circulation)
EXERCISE 20 to 30 minutes workout 4 to 5 times a week Start slowly and increase gradually Warm up and cool down for at least 5 to 10 minutes before and after workout. How Often?
Include stretching exercises.
Talk with your doctor about exercise especially if you have eye, nerve, or vascular complications. Some exercises may not be appropriate for you. Exercise every day at about the same time. Exercise soon after eating, when blood glucose levels are highest. Carry simple sugars with you. Wear well-fitting shoes and socks. Exercise Dos
Exercise with a friend if possible.
Diabetes Pills Insulin Medicines
DIABETES PILLS Diabetes pills are not insulin.
Instead, they help lower blood sugar in other ways.
DIABETES PILLS Diabetes pills work in one of three ways: stimulate the pancreas to release more insulin sulfonylureas meglitinides increase the body's sensitivity to insulin metformin thiazolidinediones slow breakdown of starches into glucose
DIABETES PILLS - stimulate the pancreas to release more insulin - generally taken one to two times daily before meals Glibenclamide / Glyburide (Euglucon, Glynorm)
Gliclazide (Diamicron, Glubitor)
DIABETES PILLS - stimulate the pancreas to release more insulin
- taken before each of three meals
DIABETES PILLS - increase the body's sensitivity to insulin decrease glucose made by the liver
Metformin (Glumet, I-max, Humamet)
DIABETES PILLS It can make you sick if you drink more than about 2 to 4 alcoholic drinks a week. nausea, diarrhea, and other stomach symptoms. These usually go away.
metallic taste in the mouth
DIABETES PILLS - increase the body's sensitivity to insulin
- taken once or twice daily with food
Nausea, vomiting and other stomach symptoms.
DIABETES PILLS Alpha-glucosidase inhibitors - slow breakdown of starches into glucose - should be taken with first bite of each meal
Acarbose (Glucobay, Gluconase)
DIABETES PILLS Alpha-glucosidase Inhibitors
stomach problems (gas, bloating, and diarrhea) that most often go away after taking the medicine for awhile
INSULIN If your pancreas no longer makes enough insulin, you need to take insulin. You inject the insulin just under the skin with a small, short needle.
TYPES OF INSULIN
Hyperglycemia and Hypoglycemia “ When controlling diabetes, blood sugar may become too high or too low. This should be taken seriously.”
Hyperglycemia Hyper (Latin) – more Glycemia (Latin) – sugar in blood +
Hyperglycemia: Causes If not treated, can lead to Coma & Death.
Hyperglycemia: Signs and Symptoms
Hyperglycemia: What to do?
Hypoglycemia Hypo (Latin) – low Glycemia (Latin) – sugar in blood +
Hypoglycemia: Causes delaying or skipping a meal eating too little food at a meal getting more exercise than usual taking too much diabetes medicine
Drinking excessive amount of alcohol
B LOOD G L U C O S E mg/dL Hypoglycemia: Symptoms & Signs LETHARGY COMA CONVULSIONS Sweating Tremor Palpitations Irritablity PERMANENT DAMAGE DEATH HEADACHE 90 - 80 - 70 - 60 - 50 - 40 - 30 - 20 - 10 -
Hypoglycemia: What to do? Have one of these quick-acting sugars: 1 or 2 teaspoons of sugar or honey 1/2 cup (4 oz.) of any fruit juice 1/2 cup (4 oz.) of regular soda
5 or 6 pieces of hard candy
Hypoglycemia: What to do? Take the right amount of medicine at the right time. Try to keep a regular meal schedule. Carry an ID card with your name and emergency response Carry fast-acting sugar at all times. Do not drive or operate equipment if you feel your blood sugar is low. Make sure family and friends know how to treat low blood sugar. If they find you not making sense or unconscious, they should take
you to the nearest hospital immediately.
Sick-day Guide Tell your doctor that you are sick. If you have a glucose meter, test your blood sugar every 4 hours. Write down the results of the test. Drink plenty of fluids if your blood sugar is too high. Try eating crackers or soup if you can't eat your usual food.
Drink clear liquids if you can't eat at all. You can eat or drink something with sugar in it if you have trouble keeping food down.
Sick-day Guide Call your doctor RIGHT AWAY if: your blood sugar is over 300 for two tests in a row you can't keep fluid down you feel more sleepy than usual
you have trouble breathing
Patient education is the key to success in diabetes management
Pancreatic Endocrine Neoplasms Account for 2% of all pancreatic neoplasms Occur anywhere along the length of the pancreas Propensity to elaborate pancreatic hormones
3 most distinctive clinical syndrome
Hyperinsulinism (Insulinoma) Most common of the pancreatic endocrine neoplasms Attacks of hypoglycemia occur with blood glucose levels below 50mg/dl The attacks consist principally of such CNS manifestations of confusion, stupor, and loss of consciousness
The attacks are precipitated by fasting or exercise and are promptly relieved by feeding or parenteral administration of glucose
Hyperinsulinism (Insulinoma) Generally benign (90%), solitary, arises within the pancreas Small (<2cm), encapsulated, pale to red-brown nodules Microscopically, giant islets with preservation of the regular cords of monotonous cells and their orientation to the vasculature
Immunohistochemistry, insulin positive tumor cells
Zollinger-Ellison Syndrome (Gastrinomas) Marked hypersecretion of gastrin by a gastrin-producing tumor Association of pancreatic islet cell lesion with hypersecretion of gastric acid and severe peptic ulceration (90-95% of patients) May arise in the pancreas, peripancreatic region, or the wall of the duodenum More than half are locally invasive or have already metastasized at the time of diagnosis
May be associated with MEN syndrome
Other Pancreatic Endocrine Neoplasm Alpha-cell tumors (Glucagonoma) Associated with increased serum levels of glucagon Presents with mild DM, characteristic skin rash (necrolytic migratory erythema), and anemia
Occur most frequently in pre- and postmenopausal women
Other Pancreatic Endocrine Neoplasm Delta-cells tumors (Somatostatinomas) Associated with DM, cholelithiasis, steatorrhea, and hypochlorydria Difficult to localized pre-operatively
Requires high plasma level of somatostatin for diagnosis
Other Pancreatic Endocrine Neoplasm Watery diarrhea, hypokalemia, achlorydria, or WDHA syndrome
Associated with increased release of vasoactive intestinal polypeptide (VIP) from a tumor
Other Pancreatic Endocrine Neoplasm Pancreatic carcinoid tumors
Endocrinologically asymptomatic despite the presence of high levels in plasma


The NSW government this week passed the Occupational Health
and Safety Amendment Bill 2011 (Amendment
Bill) and the Work Health and Safety Bill 2011
Late stage negotiations led by the Greens have seen the
inclusion in the harmonised laws of the right for Union Secretaries
to prosecute breaches of the legislation. This right will be unique
to NSW and is a further step away from the aim of harmonised laws
across the country.
In a blow to WorkCover, one of the circumstances where the
Unions will have the right to bring a prosecution is in
circumstances where the regulator has not followed the advice of
the Director of Public Prosecution regarding a Category 1 or 2
The Greens have called upon other states to include a Union
right to prosecute, bringing into question the long standing
principle in the criminal law that the prosecutor's office must
be independent and impartial.
A further last minute change to the WHS Bill was made to retain
a limited role for the Industrial Relations Court. The proposed
laws initially provided that all civil and criminal offences would
be heard in the Local or District Courts. The amended WHS Bill will
see the Industrial Court dealing with civil matters and some of the
lower end criminal offences.
The departures from the model laws passed in NSW create further
complexity for corporations operating in NSW and across state
borders. As the other states move to enact their model legislation,
it remains to be seen how far the individual state systems will
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general guide to the subject matter. Specialist advice should be
sought about your specific circumstances.
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Long experience representing many of Australia's leading employers has taught us that in employment litigation the identity of an employee's representative is a major factor in how employee litigation runs.
Treasurer Scott Morrison recently announced changes to a number of 2016 Budget superannuation contribution measures.
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text:
We live in an era where tech is rapidly becoming a part of nearly every industry you can think of — including pet products. From selfies to virtual dog sitters, technology is clearly changing how people take care of their pets.
Although a lot of pet tech gadgets are gimmicky, some of these inventions are actually efficient and fun. There are tons of incredibly useful pet gadgets emerging in the in the market for pet lovers. These gadgets incorporate the latest technology to improve the quality of life for pet and their human companions.
Whether you are looking to charm your cat or pamper your pooch with cool tech gadgets, we have done some research and compiled the best tech gadgets for pets that are guaranteed to improve the pets and the pet owners lives. The tech gadgets highlighted below cover the basic needs for playing, feeding, pet security for a happy and healthy pet.
FEEDING TECH GADGETS
The Wonder Bowl
Pets love to eat, a lot. For multiple pet owners, it can be really strenuous to make sure each pet only eats their own food especially if you have both cats and dogs. Keeping dogs out of the cats’ food and vice versa requires constant supervision.
That’s the main reason innovators came up with the Wonder Bowl. It is a scientifically developed bowl that only opens for the pet wearing the correct tag, which is included when purchasing the bowl. It is ideal for multiple pet homes and those with toddlers. It works by using infrared technology to detect when your pet is near the food bowl. When the pet wearing the unique tag is in range the lid will open granting access only to the pet you choose.
The Wonder Bowl is currently retailing at US $9.99 on Amazon.
Petsafe Drink well
Hydration is just as important for your pets as it is for you. It keeps their bodies running at the optimal level and supports essential functions such as natural detoxification in the kidneys. As important as water is for your pet’s health, many dogs and cats simply don’t like to drink it.
An automatic pet fountain creates movement to keep the water fresh, encouraging even the pickiest cats and dogs to drink more. Our top pick for the best pet fountain for dogs and cats is the Petsafe Drink well
It keeps your pets hydrated with filtered with filtered fresh tasting water. The free falling streams of water keep the water tasting clean and fresh encouraging pets to drink more. The moving water also helps inhibit the growth of bacteria which might hurt your pet’s health.
Petsafe Drink well is currently retailing at US$38.00 on Amazon.
PET PLAYTIME GADGETS
The iFetch Automatic Ball Thrower
An automatic ball thrower enables your dog to enjoy his favorite game for as long as he wants without tiring you out. These ball throwers don’t just throw the balls, but they also encourage your dog to return the ball himself. You don’t even have to be there for your dog to have a good time!
The iFetch Automatic Ball Thrower is the best ball thrower, and it’s a great tech gift for any dog because it allows dogs to play to their hearts content.. Available in the classic iFetch and the larger iFetch Too, this ball thrower is perfect for dogs of all sizes. The iFetch is designed for small to medium dogs and it launches miniature tennis balls at distances of 10, 20, or 30 feet.
The iFetch Automatic Ball Thrower is currently retailing at US$100 on Amazon.
PlayDate is literally the world’s first remote-controlled ball that allows one to play with their pets from anywhere and anytime. PlayDate gives the pet owners a unique interactive experience when playing with their pets. Owners can control the ball from either their iOS or android devices using PlayDate’s free app. They can also opt to login in through the PlayDate website to play with the ball.
The ball also features a camera mounted inside the ball which shows the pet as well as the environment they are in. A speaker and microphone are also mounted on the balls inside to let owners hear and speak to their pets.
PlayDate Currently retails at US$ 189.00
PET SECURITY GADGETS
The PetChatz HD Pet Camera
As much as one may like to spend all day every day at home baby-sitting their pets, it simply isn’t possible due to our busy work schedules. That’s one of the main reasons that the PetChatz HD Pet Camera was invented.
The PetChatz HD Pet Camera is the ultimate pet camera that enables two-way audio and video communication to keep pet owners from worrying about their pets when they are not at home.. Not only can you see your pet with live-streaming video, but he can see you as well! This pet camera allows you to capture both video and photo, saving it directly to your smartphone, and it attaches securely to the wall.
The PetChatz HD Pet Camera also dispenses treats and releases calming aromatherapy scents on command. Simply put, it is the next best thing to actually being home with your pet. It even streams live feeds from your Pet. The Camera has received amazing reviews from pet owners who have praised the durability and easy to setup design.
The PetChatz HD Pet Camera is currently retailing at $329.99 on Amazon
Link AKC Smart Dog Collar.
Gone are the days when Pets especially Dogs , only had one option of a collar- ordinary nylon collar . Tech advancements have enabled the creation of smart collars for dogs. A smart collar functions as a GPS pet tracker to keep your dog safe and many of them track vital signs and other health markers to keep your pet in great shape.
The Link AKC Smart Dog Collar is the ultimate smart collar to help you keep your dog in excellent condition. Not only does it feature advanced GPS technology that allows you to track your dog’s position, but it enables you to monitor your dog’s health and activity as well.
This smart collar monitors ambient temperature to prevent heat stroke and it features an integrated sound stimulus that can be used for training the dog. It is made with high-quality Latigo leather and comes in a wide range of sizes to fit any dog.
Link AKC Smart Dog Collar currently retails at $99 on Amazon.

domain: pet


text:
About Arcata Pizzeria
19 Yelp Reviews
londonsbestpizza9/26/21, 6:36 a.m.
Almost great but not quite. Dead in the middle of the pack in terms of Windsor pizza. Better than Franco's but outclassed by much of its competition.
420pizzaman8/4/21, 6:07 p.m.
Good crisp. Could use more sauce. Classic WOP za. Great garlic sauce

domain: food


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text:
Ashley's at the Capital
- Ask for the chargrilled oyster as an amuse bouche.
- Order every dish that has an egg in it. You will not regret it.
- You won't want to miss the Atlanta Food & Wine Festival, a celebration of everything Southern featuring Chef Lee Richardson! Make sure you pencil it in your schedule, May 30, 2013-June 2, 2013.
- For lunch, the $13 Express Lunch is a great deal. Take your time at dinner though. $49 for a 3-course prix fixe, just $20 more to add wine pairings.
- Elegant & classy, beautiful presentation , impeccable service, nothing insipid.
- Pickled shrimp, soft shell crab, banana toffee cream pie. Oh, and the best sous chef in town!
- Lemon meringue dessert - trust what the waiter recommends.
- Show your Arkansas Repertory Theatre Subscriber Card at Ashley's and receive special discounts for Rep subscribers!


"Reports of health care reform's demise are greatly exaggerated, Democrats insisted Thursday as they began emergency surgery on the fast-fading legislation," the New York Daily News writes, adding, "After a string of meetings yesterday, angry, stunned House Democrats decided they were willing to break the measure into pieces and use a loophole called budget reconciliation to pass tougher parts in the Senate."
The Times: "Even as Speaker Nancy Pelosi affirmed her commitment to pass far-reaching health care legislation this year, members of Congress and health policy experts began Thursday to deal with the reality that a smaller bill would have a better chance. Passage of a comprehensive bill looked impossible after the Democrats' loss of a Senate seat in Massachusetts. As an alternative, lawmakers in both parties said, some pieces of the bills already passed by the House and the Senate could be pulled out and packaged together in a measure that would command broad support."
Max "Speedy" Baucus proclaims, "We're going to pass health care reform. There are lots of options, and we're just talking about the pros and cons."
"Sen. Tom Harkin (D-Iowa) in the next few weeks intends to introduce legislation that would take away the minority's power to filibuster legislation," The Hill writes. "Harkin has wanted to change the filibuster for years, but his move would come in the wake of Republican Scott Brown's dramatic victory in Massachusetts… Democratic leadership aides say Harkin's bill is unlikely to succeed and that the idea hasn't been seriously considered in light of Brown's victory."
Populist outrage: "Senate Majority Leader Harry Reid (D-Nev.) said Thursday he wants more information from Federal Reserve Chairman Ben Bernanke on how to pressure banks into helping the economy," The Hill writes. "Bernanke's current term is up on Jan. 31, and Reid has yet to schedule a vote or invoke cloture on a nomination that has drawn strong criticism from some Republicans and Democrats."


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Short Escape to Kaziranga
Kaziranga National Park is one of the most famous national parks in Northeast India. It is home to a large population of the Great Indian One-Horned Rhinoceros and many indigenous species of North East India. This national park lures a large number of tourists from all over the country. With our 3 Nights 4 Days Kaziranga tour package you can indulge in adventure activities, enjoy the serene landscape, and a vacation to cherish lifelong. This tour is an escape for a wild weekend or a short getaway amid nature. During the tour, you will also get an opportunity to explore the enchanting beauty of Guwahati and visit the Kamakhya Temple which is one of the prominent Shakti Peetha. Go through the itinerary given below for more information.
Note: This is just a suggested Kaziranga Tour Package itinerary indicative of what could be possible. We customize the tour packages for your specific needs. Contact us if you want modifications so that we could tailor a Kaziranga national park tour to suit your need for a memorable trip.
- Enjoy Elephant safari rides in Kaziranga
- Spot some of the exquisite wildlife species
- Visit the Tea garden
- Explore the Orchid Sanctuary
- Enjoy the local village excursions
- Enjoy Brahmaputra river cruise
- Seeks blessings at Kamakhya Temple in Guwahati
- Enjoy shopping in GuwahatiItinerary Details
Day 1: Guwahati/ Jorhat – Kaziranga
On the day 1 of the Kaziranga Wildlife Package, our tour representative will pick you from Guwahati / Jorhat Airport. You will have an assisted transfer to the Kaziranga. Kaziranga National Park is one of the most popular places to visit in Assam. It is home to the largest population of one-horned rhinoceros in the world. The national park is a treasure trove of exotic species of flora and fauna. This UNESCO World Heritage Site is situated on the floodplains of the mighty River Brahmaputra. This national park is also officially listed as the Tiger Reserves and home to one of the largest populations of tigers in the world. With the sprawling area of 430 square kilometers, the national park is thriving with a large number of wildlife species which includes wild buffalo, gaur, leopard, stag, deer, hog, wild boar, etc.
On arrival, you will get assistance for check-in at the hotel. The rest of the time is at your leisure. You can take a stroll nearby the resort and bask in the serenity of nature.
Overnight stay at the hotel in Kaziranga.
Day 2:In Kaziranga
On the 2nd day visit Kaziranga National Park in the early morning. You will proceed for an elephant safari at 5:30 A.M to 6:30 A.M in the western part of the national park. It is home to some of the endangered species. Kaziranga National Park offers a protected environment to these species. During the safari, you will be able to found some of the exotic wildlife species which include One-horned rhinoceros, python, tiger, wild buffalo, a variety of deer, elephant, and a variety of migratory birds. Explore the national park and spot the variety of flora and fauna. You will also find a range of wildflowers, trees, and rich vegetation. It is a paradise for nature lovers and bird waters. After the exploration tour of the national park, you will return to the hotel for refreshment.
After breakfast, you will visit the nearby village to spend some time with the locals and learn about their lifestyle. You will also visit the Tea Garden and Orchid Sanctuary. Explore the tea estate and spend time amidst the aromatic plantations.
After lunch, you will again proceed to the park to enjoy another round of wildlife safari by jeep. Spend the evening spotting the exotic wildlife species and migratory birds. After the safari, return to the hotel. The rest of the time is at your leisure. You can enjoy the nature walk.
Overnight stay at the hotel in Kaziranga.
Day 3: Kaziranga – Guwahati (200 Kms. /04 Hrs.)
On the 3rd day of the tour, post breakfast you will check out from the hotel and head towards Guwahati. On arrival, you will have an assisted transfer to the hotel. Complete the check-in formalities and freshen up. Later, you will proceed to the sightseeing tour of the city. You will visit the Kamakhya Temple which is one of the 51 Shakti Peetha and is dedicated to Goddess Kamakhya. This temple is one of the most revered pilgrimage sites for Hindus. Seeks blessings here and then moves towards the river Brahmaputra to enjoy the river cruise. During the afternoon board the cruise and experience the majestic beauty of River Brahmaputra.
The rest of the evening is free for shopping. You can visit the market on your own and indulge in shopping. Guwahati has four major shopping centres including Pan Bazaar, Paltan Bazaar, Fancy Bazaar, and Uzan Bazaar. You can buy famous tea, handicrafts, Assam Silk, traditional jewelry, singing bowls, etc. from here for your loved ones.
Later, return to the hotel.
Overnight stay at the hotel in Guwahati.
Day 4: Leave Guwahati
This is the last day of the tour. Post breakfast, check out from the hotel and transfer to Guwahati Airport for your onward journey.
Price per person.
|02 Adults||INR 15,000/-|
|04 Adults||INR 12,250/-|
|06 Adults||INR 10,500/-|
Standard (3*) Hotels to be used/ Similar
|City||Hotel or similar||Room Category||Number of Nights|
|Guwahati||Cygnet Inn Repose||Superior||01|
- Accommodation using base category DBL/ Twin Room
- All transfer and sightseeing by AC Dzire/Similar with all India Tourist permit as per the itinerary; For 4 persons & above we will provide AC Innova
- 01 Jeep Safari + 01 Elephant Ride in Kaziranga
- All currently applicable taxes, however, any other tax as and when levied by the Government shall be extra.
- Any meal unless specified above.
- Any Air Fare/ Train Ticket.
- All entrances fees to monuments.
- Guide Charges
- Personal nature expenses like telephone / laundry bills etc.
- Airports tax and travel insurance etc.
- Services not specified above.

domain: travel


text:
Filming on Ant-Man might be well underway, but that hasn’t stopped the project from adding another name to its ensemble, with Martin Donovan signing on to join the cast.
The Weeds actor has agreed to take an undisclosed role in the film, and while the character’s identity is shrouded in mystery, THR describes him as “pivotal”.
Given that filming has been going on for some two months now, we’d assumed that Donovan’s role is a minor one, with possible significance to a future film.
Marvel does like to set up future movies in plenty of time, and it wouldn’t be beyond the realms of possibility to see Donovan crop up in a post-credits sequence, except for the fact that the studio tends to play them a little closer to the chest than this…
In any case, Donovan will be joining Paul Rudd, Michael Douglas, Evangeline Lilly et al, with the film set to arrive in UK cinemas on 17 July 2015.

domain: entertainment


text:
Meat & Livestock Australia managing director Richard Norton has announced a significant restructure of the company’s regional management team and approach to operations, covering key red meat markets in Asia, North America and the Middle East.
The changes, subject to industry consultation, are part of a broader process in seeking improved efficiencies for the industry service delivery company. Click here to view an earlier Beef Central article on that process.
“At the moment we have staff flying on a regular basis around the world at a cost to levy payers,” Mr Norton said, in a statement issued to staff late Friday afternoon.
“There is no doubt of the value of our work in international markets, but we need to be sure we are being as efficient as possible.”
According to the advice issued to MLA personnel and key stakeholders on Friday, the seven regional management roles will be merged into six international business management positions.
Missing from the list is current Indonesia region manager Dr John Akerman, who has resigned and will leave the company in February.
The international business managers would be responsible for all in-country activities in the markets they manage, including market access and live export where applicable. Previously, live export and boxed meat export functions were mostly treated separately.
The reduction in numbers also reflects a change to the management of the Asian region – moving away from the management of individual markets and towards an Asian Hub.
“We have seen the success of the hub approach in our management of Middle East North Africa (MENA), where we have a manager with responsibility over multiple markets,” Mr Norton said.
“We currently have highly-skilled staff located in offices through the Asian region. They have built relationships with our key stakeholders in these markets over many, many years. The proposed changes will let us leverage these skills more broadly across the region,” he said.
Under the proposed restructure, the current regional offices and their staffing will not change. However managers for the regional offices may no longer be based in that region on a permanent basis.
The restructured Asian Hub will be serviced by three IBMs:
- An IBM based in Beijing with responsibility for China, Korea, Hong Kong and Taiwan. It is proposed Michael Finucan (currently the regional manager for South Korea) will take up this position.
- An IBM based in Singapore with responsibility for Indonesia, Singapore, Malaysia, Thailand, Philippines, Vietnam, Burma and India. It is proposed Andrew Simpson (currently regional manager for China) will take up this position.
- An IBM based in Japan will remain, but will have more of a role in working with the other markets, particularly in relation to consumer marketing. It is proposed Andrew Cox will remain in this position.
The first aspect that becomes apparent from the re-deployment is that Michael Finucan assumes considerably more market responsibility than what he previously held. Added to his original focus on South Korea (Australia’s third largest export customer), is the critically-important, emerging China market (currently ranked fourth), plus Taiwan (sixth among export customers).
In addition to these changes, a new Indonesian based role is being created to focus on market access including technical trade barriers. Two strong external candidates, already currently based in Indonesia, have been identified for the role.
The international business managers located in North America (David Pietsch), the European Union (Michael Crowley) and Middle East/North Africa (David Beatty) will remain unchanged.
One of the six IBM roles will also take on responsibility as general manager of the International Markets team, Friday’s advice to staff said.
In addition to the IBMs reporting to the role, the managers of the Australian-based live export and market access programs will also report to the general manager for international business management.
The general manager will in turn report directly to the managing director.
Dependent on the outcome of industry consultation around the proposed restructure, an internal recruitment process will be conducted for this role with an announcement likely in early February, stakeholders were told.
- Click here to view MLA’s original statement.

domain: news


text:
Bufab Holding AB (publ)
PRESS RELEASE, Värnamo April 4, 2014
Bufab's Annual Report for 2013 is now available on www.bufab.com.
A Pdf version is enclosed to this press release.
For additional information, please contact:
Boel Sundvall, Director of Communication and Investor Relations
tel: +46 370 69 69 61
This information is in accordance with the Swedish Securities Market Act, the
Swedish Financial Instruments Trading Act and/or the regulations of NASDAQ OMX
Stockholm. The information was submitted for publication at April 4, 2014 at
Bufab is a trading company that offers its customers a full-service solution as
Supply Chain Partner for sourcing, quality control and logistics for C-Parts
(screws, nuts, washers,etc.). Bufab's customer offering, Global Parts
Productivity(TM), aims to enhance the productivity of the customer's C-Parts
Bufab was founded in 1977 in Småland, Sweden and has over time developed into an
international company with operations in 23 countries. The company headquarted
in Värnamo, has approximately 770 employees which are mainly active within
sales, sourcing, quality and logistics.
In 2013, Bufab's sales were MSEK 2 031 and the operating profit amounted to MSEK
201. Bufab is listed on NASDAQ OMX Stockholm, under the ticker "BUFAB". Please
visit www.bufab.com for further information
GlobeNewswire, a Nasdaq company, is one of the world's largest newswire distribution networks, specializing in the delivery of corporate press releases financial disclosures and multimedia content to the media, investment community, individual investors and the general public.
2321 Rosecrans Avenue.
El Segundo, CA 90245 Phone: (800) 307-6627 Fax: (800) 307-3567
25 Basinghall Street,
London EC2V 5HA
UK Phone: +1 866-465-8454

domain: finance


text:
Bravo Brio Restaurant Group has picked up an activist shareholder: a Los Angeles hedge fund that invests in small-cap companies that could use some help to unlock their potential for shareholders.
Red Mountain Capital Partners LLC owns about 1.43 million shares, or 5.8 percent, of the upscale casual-dining chain, which operates 94 Bravo Cucina Italiana and Brio Tuscan Grille restaurants in 30 states, including Ohio, according to a regulatory filing.Since April 1, Red Mountain has purchased 55,210 shares.
The California firm bought the shares for investment purposes “because it believed that the common stock was undervalued and represented an attractive investment opportunity,” according to a regulatory filing.
Shares of Bravo Brio, which is on an aggressive restaurant-building program and recently announced the timing of its first West and East coast openings, have risen nearly 37 percent to more than $18 since the beginning of the year. CEO Saed Mohseni has been telling shareholders that his company generates more cash than it uses to build restaurants. The company plans to add seven or eight restaurants this year. It opened two Brio restaurants — the more-polished of the chains — in Florida this year.
“Red Mountain has met with the management of (Bravo Brio) and expects to maintain a dialogue with management regarding, among other things, (the restaurant group’s) operations, strategic direction, capital structure and corporate governance, and Red Mountain’s expectation that management will pursue appropriate measures to enhance shareholder value,” the Los Angeles fund manager said in its filing.
Red Mountain did not return an email seeking additional comment.
“We have met with them, as we would meet with any shareholder,” said Jim O’Connor, Bravo Brio’s chief financial officer. “For us, it was a very normal shareholder meeting. That’s about all I can say.”
Willem Mesdag, a veteran investment banker, started Red Mountain in 2002 after retiring from the New York investment firm Goldman Sachs.
Mesdag’s firm is invested in a dozen companies with market capitalization of between$250 million and $2 billion that have “proven management teams, superior returns on invested capital, substantial free-cash flow, sustainable barriers to entry and quantifiable downside protection,” according to its website.
Red Mountain has a reputation for investing in companies in which it instigates changes to unlock shareholder value.
For example, in 2006, the firm invested in Cost Plus, operator of World Market stores, for about $10 a share. A year ago, Red Mountain and other investors helped sell Cost Plus to fellow retailer Bed Bath & Beyond for $22 a share.
In its filing, Red Mountain said it may communicate with Bravo Brio directors and shareholders, as well as potential strategic or financing partners, to help the restaurant company. The investment firm also said it might propose measures to help the company’s share price or seek seats on its board of directors.
So far, “Nothing has come out of the meeting,” O’Connor said.


Two Class of 2021 visitors coming to Allen Fieldhouse tonight
Class of 2021 small forward Kendall Brown is expected to unofficially visit Kansas tonight for game vs Milwaukee, according to his Coach Luke Barnwell.
Originally from Minnesota, Brown, a 6-foot-7, 200-pound, 4-star prospect ranked No. 17 overall in the 2021 class by Rivals.com, currently stars for Sunrise Christian in Bel Aire, Kan.
Brown, who previously visited Kansas back in October for Late Night in the Phog, has offers from Texas, Texas A&M, Arkansas, Illinois, Marquette, Baylor and Kansas, among others.
Fellow-Class of 2021 prospect Tamar Bates, a 3-star combo guard ranked No. 127 by Rivals, also will unofficially visit Kansas tonight for the second-ranked Jayhawks' game versus Milwaukee.
The 6-foot-4 Piper (Kan.) High star has seen his recruitment take off over the past year.
Missouri, Northwestern, Creighton, Kansas State, and Wichita State among others have all offered. Schools like North Carolina, Oklahoma State, Purdue, Wake Forest, and Kansas among others have shown interest.


text:
We are taking bookings with the following:
Chief Rocker Busy Bee - http://www.myspace.com/chiefrockerbusybee
Wildstyle Anniversary Celebration!
Busy Bee is the original Party Rocker! He branded the DJ while rockin' crowds. Busy Bee is a Hip Hop Pioneer, 1st Solo MC and has coined the classic's like MAKIN'CASH MONEY on SugarHill Records, WildStyle The Movie, RUNNIN THANGS on Uni w. JAZZY JAY.
need I say more...
Percee P - http://www.myspace.com/perceep
The Legendary Lethal Lyricist whom just released his long awaited classic full-legnth on Stones Throw Records, PERSEVERANCE which was completely produced by MADLIB.
Percee has a history that could be studied. check my blog http://www.wilshiredistrict.blogspot.com to read up on more percee p. ..
Wildchild - http://www.myspace.com/dajackofalltrades
Stones Throw affiliated of the legendary group LOOTPACK, Wildchild is back touring his sophmore release JACK OF ALL TRADES. With Production by Madlib, Kev Brown and features like Prince Po, Special Ed, Heiro, Percee P, Georgia Ann. Wildchild is bangin' that ole boom bap. Traditional Hip Hop and a seasoned stage show.
Team Get'em (OhNo & Roc C) - Two of Oxnard's finest team up to get'em and they're is no stopping this duo. Ill on the beats OhNo also grabs the mic and flips alongside ROC C who terrorizes the mic with passion. Both have albums released on StonesThrow and are still affiliated with STR. Join on to help us GET'EM otherwise will be gettin' you with one of Hip Hop's most dangerous duo.
Medusa - http://www.myspace.com/medusa
Gangsta Goddess has been rippin stages throughout the world and has been a staple in the Los Angeles Community for years. She is from the original LA Hip Hop GOODLIFE cypha which brought you (Freestyle Fellowship, Pharcyde, Ahmad) to name a few. Has held duties with Project Blowed.
Medusa has had releases on GOODVIBES records and most currently added on the new WILSHIRE DISTRICT compilation set to release in MAY. Medusa has also been in HBO features and Documentary FREESTYLE which also won an HBO award. Has a grammy with OZOMATLI and on LADY T Teena Marie latest release.
If any of these acts are of interest feel free to contact me at email@example.com
Peace and blessings,


text:
Mouse Monoclonal Antibody Against the Alpha Subunit of E. coli RNA Polymerase
Inventors: Richard Burgess, Nancy Thompson
The Wisconsin Alumni Research Foundation (WARF) is seeking commercial partners interested in developing a mouse monoclonal antibody that specifically recognizes the alpha subunit of E. coli RNA polymerase.
RNA polymerase is the enzyme responsible for DNA transcription, the process of making an RNA copy of a DNA gene sequence. The core RNA polymerase enzyme in E. coli consists of two alpha subunits, a beta subunit and a beta` subunit. The alpha subunits are responsible for assembling the subunits into the enzyme.
UW-Madison researchers have developed a mouse monoclonal antibody, known as 4RA1, which specifically recognizes the alpha subunit of E. coli RNA polymerase.
- Western blot experiments

domain: chemistry


text:
Cheesy Garlic Baked Chicken! This will be delish in the Deep Covered Baker! Follow my Facebook Page for more recipes, tips and Specials!! facebook.com/cookingwithcora Visit my website for your own Deep covered Baker, Outlet deals, monthly specials and Recipes, too! pamperedchef.biz/cookingwithcora
MADE THIS AND FAMILY LOVED IT....Loaded Baked Potato Soup made in the Pampered Chef Deep Covered Baker in the microwave - 30 mins start to finish, really good! I lightened it up by using only 4 oz light cream cheese, 2 tbs butter, subbed 2 cups of milk with chicken broth, and added 2 tbs flour to thicken.


text: Hi, I need advice--quick. I won an auction on eBay for a Coach bag. During the auction, the seller and I were messaging each other back and forth-- great communication. In one of the messages she said I have 5 days to return the item and she'd refund me the winning bid (no S & H and insurance which I agree with). I received the bag on 12/26. I have sent her 3 messages telling her that I'd like to return the item and if I should return it to the same address that is on the box. There are lots of scratches on the leather and a piece of the trim is peeling/coming off. She didn't mention any of these flaws in the auction listing. She has not returned any of my messages. My return timeframe is going to end soon. Should I just send the bag back or do I continue to wait til she gets back to me? Same thing with another seller... I tried contacting her 4 times and she has not responded to any of my messages. She sold me Coach dustbags that are a different size than what the auction listed. They are clearly fake. The logos in the corners are not right and the drawstrings are different... I've never filed a complaint before so I'd also like to know how many attempts should be tried before one files a complaint. Thanks!

domain: hobby


From Our Special Correspondent
Daijiworld Media Network - Bengaluru
Bengaluru, Jan 10: In tune with the tariff policy announced by the Ministry of New and Renewable Energy (MNRE) 2016, Karnataka has amended its 2014-21 Solar Policy and set an ambitious target for solar generation at 6,000 megawatts by March 2021.
The State Cabinet on Tuesday approved the changes in the policy to give encouragement to harness solar energy. The State’s solar energy potential is estimated in excess of 24,700 mw.
As per the tariff policy and targets fixed by MNRE to the State, the solar energy should constitute eight per cent of the total energy consumption, excluding hydro energy, by March 2022.
The policy of the Centre envisages that 40 per cent of the solar generation should be through rooftop, Law and Parliamentary Affairs Minister TB Jayachandra told reporters after the State Cabinet meeting on Tuesday.
The current installed capacity, including rooftop, is pegged at 400 mw.
The changes in the policy included implementation of projects with distributed generation approach spread over the State.
Now, most of the solar projects concentrated around Bengaluru.
For improving the delivery of health services, the State Cabinet approved a proposal for purchase of modern diagnostic equipment, including CT and MRI scanners, for district hospitals.
The proposal is estimated to cost Rs.103 crore. The purchase is being made as part of the government programme to provide best diagnostic services for poor patients free of cost, Jayachandra said.


text:
Publisher Audioworks/Simon & Schuster Audio, 2017.
6 audio discs (approximately 7 hr.) : CD audio, digital ; 4 3/4 in.
Call Number BOCD M CLA
Summary "Queen of Suspense" Mary Higgins Clark and Alafair Burke are back with their fourth book in the New York Times bestselling Under Suspicion series; Every Breath You Take follows television producer's Laurie Moran investigation of the unsolved Met Gala murder-in which a wealthy widow was pushed to her death from the famous museum's rooftop.
Publisher Penguin Random House Audio Publishing,
24 audio discs (30 hr.) : digital ; 4 3/4 in.
Call Number BOCD 973.917 DAL
Summary A fresh look at the many compelling questions that have attracted all his biographers: how did a man who came from so privileged a background become the greatest presidential champion of the country's needy? How did someone who never won recognition for his intellect foster revolutionary changes in the country's economic and social institutions? How did Roosevelt work such a profound change in the country's foreign relations. While all Roosevelt's biographers agree that the onset of polio at the age of thirty-nine endowed him with a much greater sense of humanity, Dallek sees the affliction as an insufficient explanation for his transformation into a masterful politician who would win an unprecedented four presidential terms, initiate landmark reforms that changed the American industrial system, and transform an isolationist country into an international superpower.
Publisher Dreamscape Media, 2017.
9 audio discs (11 hr., 2 min.) : digital ; 4 3/4 in.
Call Number BOCD ROM MCK
Summary The second book in the Bluff Point romance series returns to Bluff Point, Maine, where one woman finds love with the help of an adorable golden retriever.
Publisher Harlequin Audio,
7 audio discs (8 hr.) : CD audio, digital ; 4 3/4 in.
Call Number BOCD ROM THA
Summary Computer tech millionaire Bowie Callahan is about the last person that schoolteacher Katrina Bailey wants to work for. As far as she can see, he's arrogant, entitled, and not up to the task of caring for his young half brother, Milo. But Kat is, especially if it brings her closer to her goal of adopting an orphaned little girl. As her kindness and patience work wonders with Milo, she realizes there's more to sexy, wary Bo than she'd ever realized.
Publisher Simon & Schuster, 2017.
First Simon & Schuster hardcover edition.
x, 608 pages, 16 unnumbered pages of plates : illustrations ; 25 cm
Call Number XX(1625796.4)
Summary "In this great American story, acclaimed historian Robert Merry resurrects the presidential reputation of William McKinley, which loses out to the brilliant and flamboyant Theodore Roosevelt who succeeded him after his assassination. He portrays McKinley as a chief executive of consequence whose low place in the presidential rankings does not reflect his enduring accomplishments and the stamp he put on the country's future role in the world. Republican President William McKinley in his two terms as president (1897 - 1901) transformed America. He established the US as an imperial power. Although he does not register large in either public memory or in historians' rankings, in this revealing account, Robert W. Merry unfolds the mystery of how this bland man managed so much powerful change. McKinley settled decades of monetary controversy by taking the country to a strict gold standard; in the Spanish-American war he kicked Spain out of the Caribbean and liberated Cuba from Spain; in the Pacific he acquired Hawaii and the Philippines through war and diplomacy; he developed the doctrine of "fair trade"; forced the "Open Door" to China; forged our "special relationship" with Great Britain. In short, he established the non-colonial imperialism that took America into global preeminence. He expanded executive power and managed public opinion through his quiet manipulation of the press. McKinley paved the way for the bold and flamboyant leadership of his famous successor, Teddy Roosevelt, who built on his accomplishments (and got credit for them). Merry writes movingly about McKinley's admirable personal life, from his simple Midwestern upbringing to his Civil War heroism to his brave comportment just moments before his death by assassination (it was only six months into his second term when he was shot). Lively, definitive, and eye-opening, President McKinley resurrects this overlooked president and places him squarely on the list of one of the most important"--
Publisher Seventh Street Books, an imprint of Prometheus Books 2017.
Call Number M GRE
Summary "Detective Joe "Preach" Everson, a prison chaplain turned police officer, is coming home. After a decade tracking down killers in Atlanta, and with a reputation as one of the finest homicide detectives in the city, his career derailed when he suffered a mental breakdown during the investigation of a serial killer who was targeting children. No sooner does Preach arrive at home in Creekville, North Carolina--a bohemian community near Chapel Hill--than a local bookstore owner is brutally killed, the first murder in a decade. The only officer with homicide experience, Preach is assigned to the case and makes a shocking discovery: the bookstore owner has been murdered in exactly the same manner as the pawnbroker in Dostoevsky's Crime and Punishment. With the help of Ariana Hale, a law student and bibliophile who knew the victim, Preach investigates the local writer's community. As their questions increase, a second body is found, this time eerily resembling the crime scene in a famous Edgar Allan Poe novella. Preach and Ariana realize that their adversary is an intelligent, literate killer with a mind as devious as it is disturbed. And one or both of them may be his next target"-- "A career homicide detective returns to his small hometown and is soon asked to investigate a series of local murders with a perverse literary twist"--
Publisher Shiloh Run Press, an imprint of Barbour Publishing, Inc. /  ©2017
316 pages ; 22 cm
Call Number F PHI
Summary A faith-filled romantic comedy with a unique twist on reality show romance. Six months ago William stole Hanna's heart and then shattered it on television in front of millions of people. Now he is on her home turf in Minnesota begging her to forgive him -- and to pretend to be his fianceé! Despite Hanna's objections and the growing media frenzy, neither of them can fight their growing attraction.
Publisher Pushkin Press, 2017.
154 pages ; 20 cm
Call Number F SHI
Summary "Divorced and cut off from his family, Taro lives alone in one of the few occupied apartments in his block, a block that is to be torn down as soon as the remaining tenants leave. Since the death of his father, Taro keeps to himself, but is soon drawn into an unusual relationship with the woman upstairs, Nishi, as she passes on the strange tale of the sky-blue house next door. First discovered by Nishi in the little-known photo-book 'Spring Garden', the sky-blue house soon becomes a focus for both Nishi and Taro: of what is lost, of what has been destroyed, and of what hope may yet lie in the future for both of them, if only they can seize it." -- Provided by publisher.
Publisher Scholastic Press, 2016. ©2016
323 pages ; 22 cm.
Call Number YA F CAR
Summary Grace Blakely believed that finding the truth about her mother's murder would finally give her peace, but now she knows that it is only the beginning of the secrets that will dominate her life--and make her a target on Embassy Row in Adria.
Publisher Dutton Books, an imprint of Penguin Group (USA) LLC, . ©2005
Special 10th anniversary edition.
350 pages ; 22 cm
Call Number YA F GRE
Summary Sixteen-year-old Miles' first year at Culver Creek Preparatory School in Alabama includes good friends and great pranks, but is defined by the search for answers about life and death after a fatal car crash.
Publisher Katherine Tegen Books, an imprint of HarperCollins Publishers,
xiv, 285 pages ; 22 cm.
Call Number YA F ROT
Summary A collection of four pre-Divergent stories plus three additional scenes from Divergent, all told from Tobias's point of view, that follow Tobias's transfer from Abnegation to Dauntless, his Dauntless initiation, the first clues that a foul plan is brewing in the leadership of two factions, and the weeks after he meets Tris Prior.
Publisher StowTown Records,  ℗2015
1 audio disc ; 4 3/4 in.
Call Number CD REL BRO
Publisher F-BOMB Records,
1 audio disc (37 min.) ; 4 3/4 in.
Call Number CD POP BUC
Publisher Syco Music,  ℗2015
1 audio disc ; 4 3/4 in.
Call Number CD SOU IL
Publisher Universal Music Latino,
1 audio disc : CD audio, digital ; 4 3/4 in.
Call Number CD WOR JUA
Publisher Sony Music Latin,
1 audio disc : CD audio, digital ; 4 3/4 in.
Call Number CD WOR MAR
Publisher Louder Than Life ; 19 Recordings Ltd.,  ℗2015
1 audio disc ; 4 3/4 in.
Call Number CD POP SPA
Publisher Doubleday,  ©2015
979 pages : illustrations ; 25 cm
Call Number B SINATRA
Summary Presents a behind-the-scenes examination of the life and career of the legendary performer that offers insight into his prolific accomplishments, multidimensional character, and complex relationships.
Publisher She Writes Press, 2015.
348 pages ; 22 cm
Call Number B LAX
Summary In Uncovered, Leah Lax tells her story--beginning as a young teen who left her liberal, secular home for life as a Hasidic Jew and ending as a forty-something woman who has to abandon the only world she's known for thirty years in order to achieve personal freedom. In understated, crystalline prose, Lax details her experiences with arranged marriage, fundamentalist faith, and motherhood during her years with the Hasidim, and explores how her creative, sexual, and spiritual longings simmer beneath the surface throughout her time there. The first memoir to tell of a gay woman who spent years in the Hasidic fold, Uncovered is the moving story of Lax's journey toward finding a home where she truly belongs.
Publisher Minotaur Books, 2014.
viii, 274 pages ; 22 cm
Call Number M ALF
Summary "In early 20th century British East Africa, there are rules for the British and different ones for the Africans. Vera McIntosh, the daughter of Scottish missionaries, doesn't feel she belongs to either group; having grown up in Africa, she is not interested in being the well-bred Scottish woman her mother would like her to be. More than anything she dreams of seeing again the handsome police officer she's danced with. But more grisly circumstances bring Justin Tolliver to her family's home. The body of Vera's uncle, Dr. Josiah Pennyman, is found with a tribesman's spear in his back. Tolliver, an idealistic Assistant District Superintendent of Police, is assigned to the case. He first focuses on Gichinga Mbura, a Kikuyu medicine man who has been known to hatefully condemn Pennyman because Pennyman's cures are increasingly preferred over his. But the spear belonged to the Maasai tribe, not Kikuyu, and it's doubtful Mbura would have used it to kill his enemy. Tolliver's superior wants him to arrest the medicine man and be done with it, but Tolliver pleads that he have the chance to prove the man's guilt. With the help of Kwai Libazo, a tribal lieutenant, Tolliver discovers that others had reasons to hate Pennyman as well, and the list of suspects grows. "--

domain: library


text:
RM2K/3 Pokemon Battle System
View Single Post
June 26th, 2004 (7:03 AM).
Make it something like, he is going to use the power of the legendary pokemon for evil plans to do something.. Maybe you could be an apprentice to the one who "saves the world" instead of everything being up to you.
Pokemon Indigo League
is a re-creation of the original Pokemon TV series in game form
Joined Mar 2004
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