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San Luis Obispo CA Real Estate & Homes for Sale
115 Properties Found
The median home value in San Luis Obispo, CA is
This is
higher than
the county median home value of $569,000.
The national median home value is $231,815.
The average price of homes sold in San Luis Obispo, CA is $733,500.
Approximately 38% of San Luis Obispo homes are owned,
compared to 55% rented, while
7% are vacant.
San Luis Obispo real estate listings include condos, townhomes, and single family homes for sale.
Commercial properties are also available.
If you like to see a property, contact San Luis Obispo real estate agent to arrange a tour
1–25 of 115 properties displayed
Courtesy: BHGRE Haven Properties Mary Moloney
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Don't miss this rare creekside opportunity in the highly desirable Anholm neighborhood of San Luis Obispo, cherished for its short walk to downtown, beautiful views of San Luis Mountain, and convenient location within minutes of Cal Poly University, shopping, excellent schools, and more! This classic English-style cottage shines with all its best features, including a newly remodeled kitchen, updated bathroom, freshly painted interior, hardwood flooring, gorgeous double mantel over a wood-burning fireplace, and French doors opening to private decks. The kitchen includes all new appliances, windows, tile flooring, cabinetry and barn door slider on the pantry. Brand-new French doors from the spacious back bedroom open onto a separate private arbor-covered deck overlooking an enchanting creekside oasis. The rear yard offers a detached one-car garage with laundry hookups, upper brick patio, and private lower stone patio overlooking the creek and Orange & Lemon Trees. The perfect balance between relaxation and close proximity to the heart of downtown.
Courtesy: Richardson Properties Jennifer Campa
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Well maintained Laurel Creek manufactured home in the Silver City Mobile Home Lodge! This residence is perfectly situated to take advantage of all that Silver City has to offer-a convenient location to shopping and dining, community swimming pool, and a clubhouse with library and pool table. With approximately 1,344 square feet of functional living space, this home features three spacious bedrooms and two tastefully appointed bathrooms. Approaching the property, you are greeted by an idyllic front porch, perfect for relaxing and enjoying the beautiful Central Coast days. Take a step inside and you're surrounded with tasteful finishes and a sense of comfort and value. The inviting living room enjoys voluminous cathedral ceilings with a stylish new ceiling fan and abundant natural light. With a cozy breakfast nook, a recently updated dishwasher, new vinyl flooring, an included refrigerator, solid surface counter tops, and premium cabinetry, the kitchen and adjacent dining room are perfect for entertaining friends and family. Nestled away at the back of the residence you'll find a private owner's suite with a walk-in closet, and a luxurious bathroom complete with dual vanity sinks, soaking tub and a separate shower. Additional hi-lights include new carpet, a covered carport, storage shed, and a laundry room with included front loading washer and dryer. Don't miss this wonderful opportunity to own a move-in ready home in San Luis Obispo!
Courtesy: Richardson Properties, Inc Christie Giaquinto
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Check out this recently renovated home at Laguna Lake Mobile Home Park! This 2 bedroom 2 bathroom home has lots of beautiful upgrades. Kitchen has been completely redone with granite countertops, an island with bar seating and stainless steel appliances. New windows and canned lighting create a nice bright space with an open floor plan that flows onto the covered patio. New hard surfaced flooring throughout and don't forget all new interior paint. Both bathrooms have also been renovated with tile showers and new glass shower doors. Outside the home has been painted and new fence installed as well. There's a storage shed which is a perfect place to keep bikes. This home is ready for a new home owner! Space rent for new buyer will be $795 which covers water, sewer and trash pick up. Don't forget Laguna Lake Mobile Home Park is all ages park and has so many fabulous amenities including a swimming pool, spa, a spacious clubhouse, fitness center, and RV storage. It's an ideal location with Irish Hills behind which has hiking and biking trails and beautiful views. Close to shopping, restaurants and golf also a short drive to downtown San Luis and Morro Bay. Schedule your showing today!
Courtesy: Bond Real Estate Group Jay Bond
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Enviable location on a historic street near downtown San Luis Obispo, welcome to 1253 Mill Street. Situated on a unique 7,500 +/- square foot, R-2 lot, this property has potential to build additional units on the back side of the parcel (confirm with city/county). The darling cottage boasts history, charm, and class even outside of it's 100 + year walls! Presenting 2 bedrooms and 1 bathroom, the home offers a spacious kitchen, living + dining areas, high ceilings, faux wood flooring, and separate laundry room. Perfect for your morning coffee, and evening wine, enjoy front porch living while taking in the neighborhood views. The back deck provides even more space for entertaining, excellent for barbeques on those warm summer nights. There is an existing "Tiny Home" in the back of the lot, that is not included in the price, please inquire for additional information. Ideal as a primary residence, or rental property, the home is just blocks to downtown shopping, dining, and 101 access. Do not miss this rare opportunity to have one of the best addresses on the Central Coast!
Courtesy: BHGRE Haven Properties Colleen Clarke
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Stunning single-level home in the desirable Willowbrook neighborhood. Vaulted ceilings and the abundance of windows fills the living room with natural light. The well-designed open floor plan features two bedrooms and two baths. The entire property was recently updated with new flooring and paint throughout in a pleasing color palette. The fabulous outdoor living space includes a beautiful front courtyard with a brick patio, bordered by roses, lemon and lime trees. The backyard includes a patio and lush lawn, perfect for entertaining or private enjoyment. There are two single-car garages, providing plenty of room for parking or hobbies. This home is in a great location, close to parks, hiking trails, the Edna Valley wine trail, and just minutes from downtown San Luis Obispo. Enjoy all that the Central Coast has to offer - beaches, wineries, golfing, hiking and a great community.
6130 Madbury Court San Luis Obispo, CA 93401
Courtesy: BHGRE Haven Properties Colleen Clarke
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French Country Estate on prestigious Madbury Court! Located in one of SLO's most sought after neighborhoods, this single-level home on ½ acre in the Old Country Club is truly a rare find. With approximately 3,000 sq ft of living space, the well-designed floor plan features a formal living with fireplace, formal dining room, plus a gourmet kitchen that adjoins the family room with a second fireplace. The spacious master suite is a peaceful retreat and there are two additional bedrooms. The versatile office/library can also be used as a fourth bedroom. Large windows and skylights throughout provide an abundance of natural light. French doors from the living room, office, and master bedroom lead to the beautifully landscaped backyard, perfect for entertaining. The 3-car attached garage provides plenty of room for parking and storage. The property backs up to farmland, offering immense privacy. This great neighborhood is located in the Edna Valley just down the street from the award-winning Los Ranchos Elementary School and San Luis Obispo Country Club, offering optional membership to the golf course, tennis, swimming, restaurant and fitness center. Enjoy the Central Coast life-style with premier wineries, hiking, golf courses, beaches and Cal Poly!
217 Broad Street San Luis Obispo, CA 93405
Courtesy: Home & Ranch Sotheby's Intl Ian Chandler
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Choice property located in one of the most desirable locations in SLO. This 13,000+ sqft street to street lot, with frontage on both Broad St and Mission Lane, offers multiple possibilities. A detached 500 sqft cottage to the rear of the main house comes complete with a wet bar and full bath, making it perfect for supplemental rental income, or as a great jumping-off point for future development. The largely undeveloped top half of the property has panoramic views of the SLO Valley, the Cal Poly campus, and surrounding mountains. These amazing views, coupled with access off Mission Lane, give this parcel great lot split potential. Perched above Broad St and nestled behind several trees, the main house feels surprisingly private. An enormous front porch, Dutch front door, curved ceilings, and brick fireplace all lend to the original charm of this early 1900's redwood home, while meticulous upgrades give you peace of mind. All waste lines and the sewer lateral have been replaced continuously to the center of Broad. The bathroom, kitchen, and laundry all have new fixtures and appliances. The roof on the main house has recently been replaced and the foundation completely redone. Additional upgrades include a new water heater, electrical, newer dual pane windows in the main house, and fencing. To top it all off, this property is located within minutes of downtown SLO and sits at the base of Cerro San Luis Obispo, offering some of the area's best hiking, running, and biking trails!
Courtesy: The Avenue Central Coast Realty, Inc. Amy Daane
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Charming craftsman inspired bungalow located at the edge of the Mill Street historical district on one of SLO's most coveted streets. Talk about curb appeal! Walk through the white picket fence and up onto the covered porch & relax just moments from downtown San Luis Obispo. This little gem has the original hardwood floors and a darling built in bar/credenza. Featuring two bedrooms, one bath, kitchen, indoor laundry and a light filled family room, it is ready for you to make it your own. Lots of possibilities on this private, tree adorned R-2 lot. Don't miss out on this 20th Century treasure!
Courtesy: Real Estate eBroker, Inc. Melissa Mertogul
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Located in Creekside Mobile Home Park, this well maintained 1200 square foot, 2 bedroom/2 bathroom home features an open floor plan with a large living room opening into the dining area. The kitchen has ample storage space and quality cabinets, a pantry, and vinyl tile floors.The high quality laminate floors installed throughout the house are additional upgrades to this well maintained home. Both bedrooms have oversized closets and the large master bedroom has a walk in closet. This home includes patio with easy access to the backyard. Creekside Mobile Home Park is an affordable San Luis Obispo community with outstanding amenities such as a large community swimming pool with a whirlpool-spa-hot tub, and a beautiful community room for parties.Located across the street from Trader Joes and minutes away from the heart of downtown and dining, this pet-friendly neighborhood also features a great playground for the grandkids, an amply stocked library for your reading enjoyment, with a fitness center to help maintain an active lifestyle. The spacious clubhouse includes a billiard room and stocked game room, and there are a variety of community organized activities to help keep you entertained and involved with your neighbors. Call today to view this property and become a part of a thriving San Luis Obispo area community! This property will not last long with a space rent of only 865.00 which includes sewer and trash!!!
Courtesy: Century 21 Hometown Realty, San Luis Obispo Office Stacey Schalde
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Located in Rancho Obispo, this home is ready to move-in with 3 bedrooms, plus a bonus room and 3 bathrooms. The home has been well maintained by the original owner. A bedroom and bathroom are located on the main level of the home with a separate entrance. Upstairs, you will find 2 bedrooms and a bonus room. The second level has vaulted ceilings providing an abundance of light and views of the hills. The primary bedroom includes a walk-in closet and bathroom with double vanity. This wonderful home sits on a tree lined street conveniently located near Devaul park, hiking and biking trails, schools, shopping, restaurants and public transportation.
Courtesy: BHGRE Haven Properties April Dean
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Welcome to 1531 See Canyon Rd, an enchanting nearly 26 acre property located behind the gates of Canyon Creek Estates nestled in the desirable Avila Valley on the Central Coast of California. Canyon Creek Estates is located just a 1/4 mile from San Luis Bay Drive and this is your opportunity to own the last 2 parcels! Parcel #3 features over 3 acres showcasing an income producing 5 bedroom main home, a 3 bedroom manufactured home and a 1 bedroom apartment above the detached garage. The parcel allows for a secondary dwelling, providing endless opportunities for your Central Coast retreat. All of this is adjacent to parcel #4, a very usable nearly 23 acre Agricultural parcel with an orchard, private hiking trails, room for cows and horses, and a building envelope for a large agricultural structure. The area is surrounded by vineyards and fruit orchards so you can let your imagination soar! Located just a few minutes to Avila Beach, local wineries, world class golf, and downtown San Luis Obispo, this is truly a one of a kind property! Don't forget to click on the virtual tour!
Courtesy: Century 21 Hometown Realty, Arroyo Grande Office Alan Neumann
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Courtesy: BHGRE Haven Properties Kelly Maddalena
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Impeccable Condition Chumash Village Home that boasts "Pride Of Ownership". One of the best locations in park! 55+ Community where you own your own land. This well maintained home offers 2 bedrooms, 1.75 baths, spacious living room, dining room w/built ins and light and bright kitchen with extra pantry storage and breakfast bar. This home also includes inside laundry room with cabinets and a low maintenance back yard that backs up to quiet lot. Entertain on the wonderful covered front deck perfect for relaxing and entertaining. Great covered carport with tandem parking and storage shed. Low HOA fees ($183 mo.) Immenities! 2 pools, spa, clubhouse and RV parking. Close proximity to downtown San Luis Obispo, shopping, restaurants, beaches, wineries, hiking/biking trails, parks and transportation. This super clean home is priced to sell and won't last long.
Courtesy: Compass Sarah Weber
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This desirable, 1497sf, 3 bedroom, 2.5 bath Villa Rosa PUD was built in 1999. The unit is bright and spacious with views and multiple outdoor living areas. 2817 Garibaldi is thoughtfully designed with an open floor plan including a well-appointed kitchen. All 3 bedrooms are upstairs, and the large master suite features a spacious bath, walk-in closet & view balcony. The upper level is open and bright with multiple skylights, windows and indoor laundry. There is a 2 car attached garage with additional parking close-by. Conveniently located close to restaurants, shops & transportation, walking/bike path, YMCA & Swim Center. This beautiful home will go fast! Tenant lease in place through June 30, 2021. $2450 a month. Information not verified
Courtesy: Aurignac & Associates Anthony Aurignac
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Located in the highly desirable Rolling Hills neighborhood this custom home has exceptional views and an expansive open floor plan featuring four bedrooms and three full baths on a 1 acre lot. Walking into this single level home you will become entranced by the impeccable hardwood floors and vaulted ceilings. You'll find the living room includes a wood-burning fireplace and and opens into the kitchen while each room has an abundance of natural light. The kitchen offers expansive counter space, bar seating and stainless steel appliances. Step outside the living room onto the spectacular back patio that wraps around the back part of the home which overlooks the beautiful backyard. The backyard features amazing lawn space, mature trees and breathtaking views. On this one acre lot you have the ability to be on your own well and build a guest home. The Rolling Hills neighborhood is located just minutes from the Edna Valley, downtown San Luis Obispo and Pismo Beach, as well as being in the Los Ranchos Elementary School district.
Courtesy: Mariani Realty Robert Mariani
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Owner is in the process of moving. Please excuse all of the boxes. $10,000 Buyer Credit!! for understanding, priced accordingly. Mediterranean Architecture impeccability built by S&S Homes. Cool breezes and the best weather will delight you in the Stoneridge development. Home is on one of the highest lots in the city. This well designed spacious home features wrap-around balcony decks with majestic views of the City, Must see City lights, Cerro San Luis, and Bishops. Four separate entrances make this home ideal for hosting friends, family, or guests. Your mini farm /utopia garden has more than twenty varieties of plants and fruit trees including apples, bananas, cherry, citrus wine grapes, sapota and more. Designed by horticulturalists for the apex of health, privacy and tranquility. The Feng Shul of this home will compliment your environment and own personal touches will instantly add value.
Courtesy: RE/MAX Del Oro Hal Sweasey
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Enjoy panoramic views of the city lights and surrounding hills from the spacious rooftop deck of this stunningmodern luxury home. The 4 bedroom 3.5 bath Casona floor plan features 4 bedrooms, 3.5 baths and 2314 sq ft of living space designed by the award winning firm of Garcia Architecture & Design. Striking architecture, acute attention to detail, top of the line amenities make this one of the premiere neighborhoods in San Luis Obispo. The open concept main living area features an abundance of natural light throughout the living room, dining area, kitchen, and luxurious master suite. There are 2 decks on the main level, one accessed from the dining area with a spiral staircase to the rooftop deck and a private deck off the master bedroom. The ground level features 3 bedrooms, 2 baths and a 483 sq ft 2 car attached garage. Nestled in the South Hills, The Residences at Terraza offer low maintenanceliving with access to hiking and biking trails, a peaceful setting and less than a mile to downtown San Luis Obispo with great shopping and fine dining.
Courtesy: Blankenburg Properties Brittany Pasion
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Welcome to your bright and cozy 3 bedroom, 2 bathroom manufactured home in the highly desirable area of Edna Valley. Setting up on a hill among oak trees, this all-ages mobile home community overlooks San Luis Obispo to Bishops Peak. It is the perfect blend of quiet, rural living and easy access to all that SLO has to offer! The large, open floor plan is inviting with its high ceilings and abundance of natural lighting. The spacious kitchen opens up to the living space for seemless entertaining. The master and guest bedrooms are of generous size. The home is well maintained and has modern upgrades such as an electric car charging station. You can enjoy the added benefit of a mature garden on the side of the home that produces plenty of tomatoes, berries, peppers, and much more! This unit includes a large 8x14 storage shed. Land lease is estimated at $680 and includes water, trash, and septic
Courtesy: Richardson Prop. Christie's In John Souza
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A blend of Tuscan and contemporary style, this beautiful turnkey 4 bedroom home is located on the quaint paver lined Tresana Lane in the Toscano neighborhood. A gourmet kitchen features abundant storage with beautiful maple cabinets that have soft close drawers and doors, upgraded LG stainless steel appliances and granite counter tops. The inviting living area features a fireplace with mantle and CORE-Tec plank floors throughout that compliment the open living space. Milgard dual pane windows and 9' ceilings on both levels create a spacious natural light filled environment. The bathrooms have granite counters, Kohler cast iron tub in the guest bath and ample storage. The owner's suite features double sinks, a spacious walk in frame-less glass shower and huge walk in closet. In addition the home has full interior wall insulation throughout including the second level floor, air conditioning and tank-less water heater are also included. Outside is a tastefully designed and easy to maintain sizable backyard that is ready for a new owners personal touches. This great home is a short walk to the South Hills Open Space Trail and a short drive to many other nearby amenities in San Luis Obispo. Easy to show, schedule your appointment to see now!
Courtesy: West Coast Properties Rick Johnson
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Classic SLO bungalow in a quiet neighborhood near Sinsheimer Park. Single level 3 bedroom/2 bath with a big backyard and a detached 2-car garage. NEW: Roof, Windows, Flooring, Cabinets, Heater, and freshly painted interior/exterior makes this darling home easy to move right in. Surprising extra storage areas add personality. Good use of space with an open floor plan in the living room and kitchen. The kitchen has a new dishwasher, range, hood, sink & faucet; older refrigerator is included. The backyard is fenced in, including across the driveway, with easy access via the side kitchen door. Located near hiking trails, community pool, tennis courts, ball fields, park; a short distance to grocery, pharmacy, and hospitals. Add your finishing touches to this home and yard to reflect your own personal style.
Courtesy: Merrill & Associates Real Estate Shonda Merrill
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Welcome to 1255 Orcutt Road #B46 located in Colonial Manor Mobile Home Park (an ALL-AGES park)! This updated mobile home features 2 bedrooms, 1 bathroom, indoor laundry, and a spacious yard! Upon entering, you will appreciate vaulted ceilings and an open concept living room, kitchen, and dining area. This beautiful home boasts large windows which allow for plenty of natural light. Engineered wood flooring throughout compliments the white kitchen cabinetry and beautiful granite countertops. As you make your way down the hall, you'll notice the attention to detail that went into upgrading the full bathroom with a gorgeously tiled shower and tub, granite countertops, and tile flooring. Highlighted in the roomy Master Bedroom is a large closet and private access to the yard where there is ample room for outdoor entertaining and a shed situated in the back corner of the yard that may be great for storing your home gardening or home improvement tools. Also remaining with the home is a mature lemon tree…Don't miss this opportunity to own an affordable, attractive, turn-key residence with schools and shopping nearby!
Courtesy: Eighty20 Group Farid Shahid
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The Ridge at Monterey Heights - Lot 1 - A contemporary new construction home with attached Accessory Dwelling Unit (ADU 2nd Unit) perched on the hill in one of San Luis Obispo's most desirable neighborhoods. Centrally located near Cal Poly and only minutes to Downtown SLO, the Monterey Heights neighborhood caters to families and students alike. The home is expertly designed by award winning architects TenOver Studio to maximize views and functionality. The Ridge offers a spacious open floor plan with abundant natural light and picturesque mountain views. This 3,200± Sq. Ft. home includes 5 bedrooms and 2.5 bathrooms with an attached 1 bedroom + 1 bathroom ADU below.; ideal for a large family or an investment property. Premium modern amenities include: custom solid wood cabinets certified by FSC, Tier 1 Caesarstone quartz countertops, engineered oak hardwood floors by Shaw, and GE Monogram professional grade appliances. The large wraparound deck allows panoramic views of the surrounding hills with ample space for entertaining guests. The Ridge is a true Net-Zero energy efficient home with 100%-Owned rooftop solar power, LG Chem Battery for onsite energy storage, and two ChargePoint electric vehicle chargers installed in the garage. Come experience contemporary living at The Ridge at Monterey Heights and schedule a walk-through. Construction Completed: September 2020.
Courtesy: Wilson & Co. Sotheby's International Realty Erica Abbott
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Progressively designed for a modern way of life! Recent extensive renovations throughout added exceptional quality finishes and the latest décor. The gourmet galley kitchen features polished quartz countertops, stainless steel Bosch appliances and decorative Italian graffiti tile backsplash. Complimented by European driftwood white oak floors, custom cabinetry and solid core doors, Lutron lighting system, hardwired speakers and dramatic vaulted ceilings. The Main bedroom features a custom built-in closet made of ash. There is also a loft with custom bedding pad for guests. Two private outdoor decks are made of slate and overlook lush landscaping. The one car garage is carpeted and features ample storage. Located on a prominent corner of the complex to allow maximum natural lighting and privacy. This is the perfect full-time residence or part time vacation pad in SLO. With easy accessibility to downtown and exceptional access to French hospital. Located on a prominent corner of the complex to allow maximum natural lighting and privacy.
Courtesy: Hybrid Homes Team Thomas Darosa
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South Peak Tiny home community is now completely renovated and available for new /used in park home Sales, now accepting deposit and reservations to purchase available units, the owner builder of South Peak has now released the first 3 new home for viewing and sale, if you have client who wishes to purchase any of the new/used Manufactured Homes or Tiny Homes? Contact the onsite community manager direct , if you refer an interested buyer & who buys a new/used manufactured home or a Tiny Home (RV) in South Peak, owner has agreed to compensate with a referral if customer is register with the property managers by calling . Any agent or potential buyers can call or visit the on-site Manager direct with all questions. Do not email listing Broker of record. Buyer agent must present referral agreement to management on site office to receive compensation, all referral are paid by owner/builder as commission at close of escrow, All deposit checks for Manufactured Homes make Payable to Allred Escrow and for Tiny Homes (DMV) deposit check payable to seller "South Peak". All document must be HCD.
Courtesy: Hybrid Homes Team Thomas Darosa
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South Peak Tiny home community is now completely renovated and available for new /used in park home Sales, now accepting deposit and reservations to purchase available units, the owner builder of South Peak has now released the first 3 new home for viewing and sale, if you have client who wishes to purchase any of the new/used Manufactured Homes or Tiny Homes? Contact the onsite community manager direct , if you refer an interested buyer & who buys a new/used manufactured home or a Tiny Home (RV) in South Peak, owner has agreed to compensate with a referral if customer is register with the property managers by calling . Any agent or potential buyers can call or visit the on-site Manager direct with all questions. Do not email listing Broker of record. Buyer agent must present referral agreement to management on site office to receive compensation, all referral are paid by owner/builder as commission at close of escrow, All deposit checks for Manufactured Homes make Payable to Allred Escrow and for Tiny Homes (DMV) deposit check payable to seller "South Peak". All document must be HCD.
1–25 of 115 properties displayed
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Sazerac Rye Whiskey Kit
12 Cocktails / Soul Rush
Pick & Mix with Sazerac Rye
One of the original greats of the American whiskey world pairs perfectly with one of these three Sourced fresh cocktail mixes!
Sazerac Rye Whiskey
The One and Only New Orleans Original Sazerac Rye Whiskey symbolizes the tradition and history of New Orleans.
Rye Whiskey dates back to the early 1800s, around the time when saloons, veiled as Coffee Houses, began lining the streets of New Orleans. It was at the Sazerac Coffee House on Royal Street where local patrons were served toddies made with Rye Whiskey and Peychaud's Bitters. The libation become known as the "Sazerac" and America's first branded cocktail was born. This is the whiskey that started it all!
We feel the world's foremost whiskey expert, Jim Murrary describes the taste best: "Any crispier and the glass would shatter…a rare and valuable gem."
Soul Rush Mix: We certainly believe that Whiskey is good for the soul! So we made a refreshing cocktail mixer to go with a fine whiskey! Featuring freshly squeezed lemon juice, homemade elderflower syrup, and Bittermen's Elemakule Tiki Bitters, the Soul Rush allows the whiskey to ring true with highlights of the island trade winds.
Black Cherry Old Fashioned: This delicious mixer honors the tradition found in the basic chemistry of a classic Old Fashioned – sugar + bitters – and offers a modern riff. Featuring fresh tart cherry juice with Bittermen's Burlesque Bitters, the Black Cherry Old Fashioned is modern enough to convert a first time Old Fashioned drinker while respectful of the traditional balance to please the classics!
Maybe Tomorrow: Yep – as the name suggests, this mixer is gonna be just the right amount of wrong! As in: "Oops, I think I had three of those…I guess I'll maybe get to that tomorrow!" Featuring homemade demerara syrup, Chocolate Bitters and vanilla extract, we've taken the ole stand by Old Fashioned concept to a dangerously drinkable place! Maybe Tomorrow… :)
Your Delivery Includes:
- A 750mL of Sazerac Rye
- A bottle of all fresh ingredients batched together to make 12 cocktails
- A jigger to help you measure out each cocktail
- A menu with instructions on how to mix your cocktail
- 4 high-quality Sourced branded plastic cups

subset: commoncrawl


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Editor's Note
Editor's Note
PRIME Contest
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Starting a business has rewards beyond a paycheck
Debbie Gardner
PRIME – April 2013
By Debbie Gardner
Much like the three local residents I've written about in this month's feature story, I too have dipped my toe into the world of owning a business. No, I wasn't as brave as the individuals whose stories I chronicled for the paper. My business venture didn't involve figuring out what I was good at, or sinking a lot of time and money into a new concept. My self-employment foray was more of a sure thing, or so I thought. I decided to join one of the popular direct selling companies that had recently moved into our area. I'm certain you all know what I mean by direct sellers – after all who hasn't been invited to attend a Tupperware or Tastefully Simple or Princess House party by a girlfriend, granddaughter or niece? The shows are usually fun, and, in most cases, it seems to attendees that everyone is eager to buy the product. For someone like myself who might be dreaming about staying home with a child but still contributing to the family bottom line – my husband and I had just adopted our son, Evan, when I decided to give direct selling a try – the concept is very persuasive. But as I said, I dipped my toe in business ownership. I started the direct selling business while still maintaining my regular job. It was a smart move. Whatever the company name, the start-up process is the same for a would-be business owner such as myself. You purchase a pre-set kit of products and supporting paperwork, and the company provides training, either through a local longtime member of the company (either called a team leader or director), or through online courses and videos. Some companies – the good ones – provide newbies with both live and online support in an effort to insure initial success. And, I'll admit, success did seem easy in the beginning. I had plenty of support from family and friends when i announced I had decided to give xyz company a try. Many were willing to help me get off to a good start by hosting parties, or helping to put me in touch with friends or family members whom they knew were interested in the type of product I was offering. But – that kind of momentum doesn't keep going forever, and after a time I – and anyone else who has ever tried this kind of business – learned that owning a business requires an investment of your time and effort. I didn't go into the business world completely blind and naive – as eMarketing Strategy owner and sought-after marketing consultant Ruth P Stevens notes in her advice to would-be business owners on page 5, I did choose a direct sell product that fit my skills and experience. I also developed a business plan with goals – which I did meet in the initial phase. Where I fell down was in the all-important area of networking and contacts. I'm not a bubbly, outgoing person by nature, and striking up a conversation that might develop into a business lead did not come as easy to me as it did to other direct sellers I talked to. I also suffered from phone phobia – I had a hard time making the all-important follow-up phone calls to ask individuals who had attended one of my presentations if they were interested in hosting their own party. Stevens would have chided me that I hadn't figured out how to network on my own terms, and in a way that better fit my personality. Still, I learned a lot about running a business – things such as scheduling (even if it was just my own time for parties, submitting orders and networking), cash flow, customer service, public speaking, promotion – both product and self , and business analysis. I learned to be resourceful – there were always times when the product didn't work correctly, the host was not prepared for my demonstration or the attendance was dismal – and I had to figure out how to salvage the event for the host on the fly. Being in business for yourself definitely teaches you to think, as it's said, "out of the box." I also learned a lot about myself – and that I probably couldn't turn my self-employment dream into a reality, at least not with the business I had chosen. In my eyes the true profit I made came from the experiences I gained and the friends I made, both clients and fellow direct sellers, as I struggled to succeed. I haven't given up – one of my strengths, it seems, is perseverance. I'm still in the direct selling game. Only now, my goal is just to help fund Evan's gymnastics.


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FW Beauty
Silver Elixir, Acne Therapy Facial Oil
There is a whole list of acne-busting ingredients in our Silver Elixir. Helps to reduce redness and irritation to treat current acne/breakouts, it also helps to even out skin tone and texture, hydrating and nourishing your skin to minimise the appearance of acne scarring.
Formulated with renowned ingredients for its regenerative powers and rich in healing linoleic acid; moisturising and irritation-preventing. Bacteria-busting tea tree oil, which has been used as a traditional medicine by Aborigines for centuries.
Silver is known for its anti-fungal, antibacterial and anti-inflammatory properties & topically can help treat everything from rosacea to acne to aging. Silver was first used in 1891 by a surgeon named B.C Crede to sterilize wounds. The use of silver grew in popularity between 1900 to the 1940s. Tea tree oil is a popular choice for treating acne because of its anti-inflammatory and antimicrobial properties. It's thought to calm redness, swelling, and inflammation. It may even help to prevent and reduce acne scars, leaving you with smooth, clear skin.
How to use:
ALWAYS DO A PATCH TEST beforehand to check for sensitivity. To be applied after your serum on clean skin. 1-2 drops massaged into the skin until absorbed. To be used daily. Suitable for acne/breakout prone skin.
Related articles:
www.observer.com "Why You Want to Add Silver and Copper To Your Skin Care Routine" BY KAYLA JACOBS 28 DECEMBER 2017 https://observer.com/2017/12/why-you-want-to-add-silver-and-copper-to-your-skin-care-routine/
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Puttur constituency, with its agrarian background, is known for arecanut trading. The only chocolate factory managed by a cooperative sector Campco, Directorate of Cashew Research, under the Indian Council of Agricultural Research (ICAR) is stationed at this region.
Puttur is the birthplace of Koti and Chennayya, the twin heroes of Tulu Nadu, at Padumale. In addition, it is also the place where Jnanpith awardee Shivaram Karanth spent a major part of his life at Balavana.
Going by the history of the constituency in the past 13 Assembly elections, the Congress has won eight times, while the BJP won five times. The then Janata Paksha won once in 1978.
Sitting MLA Shakunthala T Shetty, who was earlier with the BJP, had contested against B Ramanath Rai of the Congress from Bantwal constituency in the 1994 and 1999 elections and had lost.
Later, the BJP fielded her from Puttur in 2004 where she won. After the BJP denied her a ticket for the 2008 election, she contested as an Independent with the support of BJP MLA K Rama Bhat, who rebelled against the BJP.
He supported her by forming the Swabhimani Vedike.
Shakuntala secured 25,171 votes (20.4%), while Mallika Prasad of the BJP won by securing 46,605 (37.77%) votes. She joined the Congress in the last Assembly election and won against Sanjeeva Matandoor with a margin of 4,289 votes.Shakunthala Shetty had secured 66,435 votes (46.46%) while Sanjeeva Matandoor secured 62,056 (43.45%), Dinesh B N of JD(S) secured 6,625 (4.64%) and Aboobakkar Siddiq of SDPI secured 4,442 (3.11%) votes, Shekar Madavu (Independent) polled 1,834 (1.28%) and Jayaram Bhat Madavu (KJP) polled 1,506 (1.05%) votes.In this election, there are 11 candidates in the fray—I C Kailas Gowda JD(S), Shakunthala Shetty (Congress), Sanjeeva Matandoor (BJP), Abdul
Majeed Kolpe (JD(U)), Shabana S Sheik (MEP), B Shekar Madavu (Praja Parivarthana Party), M Sheshappa Rao (Samanya Janata Party), Abdul Baseer Boodiyar (Independent), Amarnath B K (Independent) and Vidyasri (Independent).
Ashok Kumar Rai and Arun Kumar Putthila, the MLA ticket aspirants from BJP in Puttur constituency, were not happy with Sanjeeva Matandoor being made the party candidate. Party sources claim that all such differences have been sorted out and the workers are united. On the other hand, former Puttur block president Kavu Hemanath Shetty was also a contender for a ticket in Congress.
The constituency has the highest Endosulfan victims in Dakshina Kannada. Of the 3,628 Endosulfan victims identified in the district, 1,560 victims are in Koila, Alankaru, Vittal and Panaje. A daycare centre for the victims has been set up at Koila. However, a permanent rehabilitation facility is a long–pending demand of the families of Endosulfan victims.
Upgrade of government hospital to a 300-bedded hospital, setting up of a medical college, shifting of SP office to Puttur, development of Bendru Theertha (only hot-water spring in South India), Koti-Chennaiah birthplace Padumale, Birumale Gudda and Karanth's Balavana are the needs of the constituency.
In addition, Nellikatte has a school where Shivaram Karanth had carried out theatre activities. The Ranga Mantapa needs a facelift. There is also a demand to declare Savanoor as a hobli centre. In addition, there are a few bridges, including Chelyadka that submerges during monsoon which needs to be developed.
Sitting MLA Shakunthala Shetty, after submitting his nomination, had said, "The election is between development and false propaganda on the development works initiated by me. I have responded to the woes of the people through development works."
On the other hand, Sanjeeva Matandoor feels that the claim of development is far from reality. Delay in execution of projects has also upset the people in the constituency. BJP has taken up intensive campaign in all the 217 polling booths in the constituency. Congress feels that development works, check on communal clashes and non-corrupt image of Shakuntala's image will be a plus point in the election.
With just a few days left for the election, speculations are rife from all quarters about the fate of the candidates. Now, the question is whether the voters will give another chance to the Congress or vote for change.


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A Novel 2D Feature Extraction Method for Fingerprints Using Minutiae Points and Their Intersections
The field of biometrics has evolved tremendously for over the last century. Yet scientists are still continuing to come up with precise and efficient algorithms to facilitate automatic fingerprint recognition systems. Like other applications, an efficient feature extraction method plays an important role in fingerprint based recognition systems. This paper proposes a novel feature extraction method using minutiae points of a fingerprint image and their intersections. In this method, initially, it calculates the ridge ends and ridge bifurcations of each fingerprint image. And then, it estimates the minutiae points for the intersection of each ridge end and ridge bifurcation. In the experimental evaluation, we tested the extracted features of our proposed model using a support vector machine (SVM) classifier and experimental results show that the proposed method can accurately classify different fingerprint images.
feature extraction, fingerprint images, minutiae points, support vector machine,
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DOI: http://doi.org/10.11591/ijece.v7i5.pp2547-2554
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This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
ISSN 2088-8708, e-ISSN 2722-2578


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MDF tags are one of my favourite things to do. They can be used as an alternative to sending a card or even given as a gift. For this project, I fancied making a massive shabby chic tag using neutral colours. I have a good stash of lace and crocheted … Read More
Words of encouragement – Ink and stamp card
I love a good sentiment and 'Mamamakes' sentiment stamps are some of the best out there! So I chose 'Don't let anybody dull your sparkle' sentiment from 'Shine Bright' jumbo stamp set and started there. I'm sure everyone has some Tim Holtz distress inks and I can't blame them! They … Read More


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I feel badly because I have not done my blog in what feels like eons. So much has been going on and, for most of it, I have been sick.
I flew back from Cannes to Atlanta. A very nice couple is renting my gorgeous loft and so I stayed in a hotel. That is so weird: being in a hotel in a city that was your home for almost 20 years. But when I walked out the front of the hotel to walk Tulea (who I was reunited with the moment I got off the plane 🙂 the first morning, I heard someone call, "Hi Jane!" and I looked up and there was a dear friend in a passing car. See, that's one thing I love bout Atlanta: it is a big-ish city with all the culture and goings-on of a really big city, but you run into friends all the time. It's manageable. You can wrap your heart and mind around it. I got a little home sick there for a few days. I also got real sick. Maybe it started with the pollen and turned into a major upper respiratory deal. Who knows. I was pretty tired and run down after Cannes and it is harder to get over jet lag at my age (wish I could remember that when I accept to fly places) so I was vulnerable. By the time I got back to L.A. I as feeling really rotten but I had these interviews and photo shoots and stuff to catch up on. I got onto antibiotics and got well and then I flew to San Francisco for a fundraiser for the First Annual Food Day in DC next Oct (more about that coming up!) and it was 50 degrees there and I got sick again. Then I had an amazing, high fashion photo shoot for Harpers Bazaar that will come out this fall, I think. OMG the clothes were spectacular. Especially a Stella McCartney dress, all black but with a wide, sheer panel up one side with large black polka dots on it. Wait till you see!
Speaking of McCartney, I can't forget to tell you something truly special: Paul McCartney and his fiance, Nancy, came for dinner at Richard's and we had the best time!!! The evening ended with Paul playing Richard's Art Deco piano (from the Queen Mary Cruise ship in the 1930s). Richard fortunately had it tuned that very afternoon. It (and Paul) sounded terrific. In spite of being sick, I had a really great time and thoroughly enjoyed talking to Nancy.
The next day, I taped Oprah's program, Master Class, for OWN which will air sometime this fall, I'm told. I so wanted it to be good. (You'll tell me if it was good when the time comes!) The producer and director told me it was good. As you may (or may not) know, Master Class, is a program in which someone chosen by Oprah, who she feels has life lessons to pass on, talks for an hour, straight into the camera, in close-up. The conversation is interspersed with photos, film, home movies, things that illuminate what the person is saying. I watched a number of them to prepare myself. I was especially moved and illuminated by the ones done by Maya Angelou and Sidney Poitier. Needless to say, I felt honored that Oprah asked me. I did my best although I was not feeling well and then, straight from there, I went to the Beverly Hilton to receive the UCLA ICON Award. Jennifer Lopez presented it to me which really moved me as I know how busy that woman is. It meant the world to me that she took time to do that. At my table were (besides Richard) my BFF Paula Weinstein, her daughter, Hannah Rosenberg (my goddaughter), my brother Peter and his fiance, my step-mother, Shirlee Fonda, Jason Alexander (who was MC), George Segal and his wife (we did "Fun with Dick and Jane" together), a wonderful retrospective of my film clips was shown and a lot of money was raised for UCLA's Longevity Center.
"Entertainment Tonight" Video Clip: Jennifer Lopez presented Jane Fonda with the UCLA Longevity Center Icon Award (click to play)
"Extra" video clip: Jane Fonda honored at UCLA's Longevity Center event (click to play)
I was supposed to fly to New York today for Eve Ensler's birthday party and a big V-Day event. Eve is one of my closest and fiercest friends and I am on the board of V-Day and the last thing I wanted to do was miss this. And the board meeting tomorrow. But I knew, and my doctor told me, I must not fly for awhile till I am all well. Well—that's all for now. Sorry about my absence.


text: Displaying 1 of 1 2007 Title: Diary of a wimpy kid: Greg Heffley's journal / by Jeff Kinney. Format: Book Author: Kinney, Jeff, author, illustrator. Publisher, Date: New York : Amulet Books, 2007. Description: 217 pages : illustrations ; 21 cm. Summary: Greg records his sixth grade experiences in a middle school where he and his best friend, Rowley, undersized weaklings amid boys who need to shave twice daily, hope just to survive, but when Rowley grows more popular, Greg must take drastic measures to save their friendship. Series: Kinney, Jeff. Diary of a wimpy kid (Series) ; 1. Subjects: Middle schools -- Juvenile fiction. Friendship -- Juvenile fiction. Schools -- Juvenile fiction. Diaries -- Juvenile fiction. Genre: Diary fiction. Humorous fiction. Other title: Greg Heffley's journal Notes: A Junior Library Guild selection LCCN: 2006031847 ISBN: 9780810993136 (paper over board) 0810993139 (paper over board) 9781428733565 (FollettBound) 1428733565 (FollettBound) 9780810994553 (pbk.) 0810994550 (pbk.) 9781419716317 (pbk.) 9780810988934 0810988933 9781419712760 9780606236621 (Turtleback books) 0606236627 9781419741852 (hardback) 1419741853 (hardback) Other Number: 74029165 Control Number: 2034243 Total Owned in SHARE 720 # Available: 483 Current Holds: 2 # Local items: 4 # Local items in: 2 Course Reserves: 0 Request It Please select and request a specific volume by clicking one of the icons in the 'Available?' section below. Add to My List Share Expand All | Collapse All Available? Map It Suggestions and more Large Cover Image Librarian's View Displaying 1 of 1


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Honors College Dean Selected As Aspen Presidential Fellow
Pascale Charlot, dean of The Honors College, has been selected as an Aspen Presidential Fellow for the upcoming 2019-2020 class.
Charlot, who received the award on April 12, will begin the ten-month fellowship in July. She will participate in three residential sessions, receive leadership mentoring and complete a Capstone Project.
"I'm very excited," Charlot said. "I think it's important for leadership voices to represent different kinds of experiences."
The Aspen Presidential Fellowship recognizes leaders in higher education committed to transforming community colleges to ensure student success. Charlot, one of 40 candidates to receive the fellowship, was selected for her abilities to take strategic risks, lead students and cultivate partnerships.
As Honors College Dean, Charlot has overseen the program's administration across four Miami Dade College campuses' for seven years. She received bachelor's degrees in sociology and economics from Duke University in 1991 and later pursued a juris doctorate from the University of Michigan in 1996.


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ReportsnReports.com Adds "Global Frozen Fruits Market Research 2019– Global Industry Growth, Opportunities, Trends Assessment, in-Depth Analysis" To Its Research Database.
The "Global Frozen Fruits Market" report provides realistic and functional details of the Frozen Fruits market, which assist you in promoting ideas with research-based factors. It offers in-depth knowledge, refines variations of the global Frozen Fruits market to assist you in judging the general strategy.
Download sample report copy of Global Frozen Fruits Market 2019 @ https://www.reportsnreports.com/contacts/requestsample.aspx?name=1842932
Asia-Pacific frozen fruits market is expected to flourish at a significant rate over the forecast period. Factor such as, increasing online purchase of staple food is anticipated to drive the growth of the frozen fruits market over the forecast period.
United States is anticipated to account for a significant portion of market share in the overall market of frozen fruits during the forecast period.
# The key manufacturers in the Frozen Fruits market include Uran Food Group, Pinnacle Foods, Kendall Frozen Fruits, Ardo, SunOpta, Welch Foods, Kerry Group, Hain Celestial, Foodnet, Welch's Foods, Newberry International Produce, Titan Frozen Fruit, MDC Foods, General Mills, Findus Sverige.
Market segment by Type, the product can be split into
– Red Fruits & Berries
– Tropical Fruits
– Citrus Fruits
Market segment by Application, split into
– Confectionery & Bakery
– Jams & Preserves
– Fruit-Based Beverages
– Dairy
– Others
The report pinpoints on the leading market competitors with explaining Frozen Fruits company profile depends on SWOT analysis to illustrate the competitive nature of the Frozen Fruits market globally. Even more, the report consists of company recent Frozen Fruits market evolution, market shares, associations and level of investments with other Frozen Fruits leading companies, monetary settlements impacting the Frozen Fruits market in recent years are analyzed.
Complete data will assist the customer better understand the rivals. Besides, this research document contains estimation from a global aspect, which reveals a regional expansion class, along with market size, scope and benefit, and expenditure data.
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Geographically, this report is categorized into various main regions, including sales, proceeds, market share and expansion Rate (percent) of Frozen Fruits in the following areas, North America, Asia-Pacific, South America, Europe, Asia-Pacific, The Middle East and Africa.
Major Points from Table of Contents
Chapter 1 – Frozen Fruits Market Overview
Chapter 2 – Global Frozen Fruits Competition by Players/Suppliers, Type and Application
Chapter 3 – United States Frozen Fruits (Volume, Value and Sales Price)
Chapter 4 – China Frozen Fruits (Volume, Value and Sales Price)
Chapter 5- Europe Frozen Fruits (Volume, Value and Sales Price)
Chapter 6 – Japan Frozen Fruits (Volume, Value and Sales Price)
Chapter 7 – Southeast Asia Frozen Fruits (Volume, Value and Sales Price)
Chapter 8 – India Frozen Fruits (Volume, Value and Sales Price)
Chapter 9 – Global Frozen Fruits Players/Suppliers Profiles and Sales Data
Chapter 10 – Frozen Fruits Maufacturing Cost Analysis
Chapter 11 – Industrial Chain, Sourcing Strategy and Downstream Buyers
Chapter 12 – Marketing Strategy Analysis, Distributors/Traders
Chapter 13 – Market Effect Factors Analysis
Chapter 14 – Global Frozen Fruits Market Forecast (2019-2025)
Chapter 15 – Research Findings and Conclusion
Chapter 16 – Appendix
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BCHS Volleyball Banquet
Monday, November 11th, the BCHS Volleyball team had their 2019 banquet. The coaches talked about highlights of the year and recognized players for team and individual achievements. The Junior Varsity team ended the season with a 12-4 record. This was by far the best season any JV team has had. Coach Flener mentioned how happy he was with the girl's progress and that they had made huge improvements throughout the year. Coach Minton discussed the 14 individual records that were broken this season along with the team record of 15-9. She also mention how proud she was that the girls had a combined GPA of 3.56. Listed are all the awards from the banquet.
Freshman Awards
Most Serves, Most Aces, and MVP : Jenna Johnson
Most Digs and Most Kills: Olivia Johnson
Most Improved: Alyssa Barton
Sportsmanship: Liberty Franzell
Most Team Spirit: Maggie Childress
Most Hustle: Olivia Johnson and Emily Cunningham
Junior Varsity Awards
Most Serves: Lexa Johnson
Most Aces and MVP: Autumn Gidcumb
Most Digs and Most Hustle: Abby Dockery
Most Assist: Alexis Burdin
Most Kills, Most Blocks, and Most Improved: Grace Embry
Sportsmanship: Carley Jones
Most Team Spirit: Kayla Green and Abby Dockery
Varsity Awards
Most Serves, Most Aces, and MVP: Autumn Gidcumb
Most Digs and Most Hustle: Abigail Dockery
Most Assist: Lillian Gidcumb and London Howard
Most Kills and Sportmanship: Delaina Flener
Most Blocks and Most Improved: Grace Embry
Most Team Spirit: Kayla Green


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Phishing fraudsters have come up with a new way to capture the attention of users and access their Facebook passwords, and in the form of pop-up logs that now appear on malicious websites.
Single sign-on or SSO is a pop-up option that allows users to use their Facebook, Google, LinkedIn, or Twitter accounts to log on to other websites. The option is designed to make life easier for both users and website creators, since it is not necessary to create and remember passwords for hundreds of different sites, but access is enabled based on already created accounts on certain platforms. Thanks to the encryption, the sites to which users log in under normal conditions do not receive information about their passwords and user names, or it has been so far. Namely, as part of the new malicious attacks, a pop-up log window (SSO), almost identical to the Facebook SSO, appeared, only it does not support the Facebook API, and in fact is not in any way tied to this social platform, so instead of easier logging this system actually steals Facebook passwords and usernames.
Although the SSO copy is pretty convincing, it has almost the same elements as the original Facebook window for logging onto other sites, there are some differences that could indicate to users that it's a fraud – the original CSS from Facebook and Google can to be moved within the site to which the user logs without changing its appearance, and the layout of the field, while the parts of the false SSO disappear when attempting to move the window.
This convincing counterfeit is that users and security experts remind that attacks become more serious, and that multifactor authentication is the best solution for such problems.


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Nonviolence, Peace, and Catholic Higher Education
Catholic college and university students have a special role to play in helping share the peace of Christ by carrying a message of hope into their daily lives
By Marc Tumeinski, PhD
At the Last Supper, Jesus gives the disciples a message of hope: "Peace I leave with you; my peace I give to you; not as the world gives do I give to you" (Jn 14:27). This is a blessing as well as a daily challenge, both of which we are reminded of at every Mass when we hear those words. As a witness to this message, Peter reminds Christians to "always be prepared to make a defense to anyone who calls you to account for the hope that is in you" (1 Pt 3:15).
Since 2016, the Catholic Nonviolence Initiative (CNI) has sought ways to share this message of hope and peace by affirming the vision and practice of active nonviolence at the heart of the Catholic Church. Our goal is a just peace, consisting of political cooperation for the common good, respect for the dignity of all persons and the natural world, preventing violence before it begins, and the transformation of violent conflict by nonviolent strategies. To accomplish a dynamic and generative just peace has always been the defining goal of the Catholic social vision. While peace is the comprehensive and ultimate political goal, social, economic, and ecological justice is also essential to peacemaking.
This Christian message of hope and peace is given to every generation. Consider the situation we are facing today and what this means for universities, students, faculty, and staff. "The coronavirus has upended communities around the world, threatening livelihoods and lives, forcing a previously unthinkable change in daily routines, helping everyone to recognize the fragility of life and the deep injustice that leaves too many people, communities, and countries vastly more vulnerable than others," said CNI executive committee member Marie Dennis. "Perhaps this pandemic will help us to recognize the critical need for a transformative shift away from violence in our values and priorities… This time of crisis is urgently calling for a new understanding of security that is based on diplomacy, dialogue, reciprocity, and a multilateral, collaborative approach to solving very real and critical global problems."
Students, particularly those at Catholic colleges and universities, have a special role to play in solving these problems, not least by carrying a message of hope into their daily encounters, thus helping share the peace of Christ.
Teaching Peace and Nonviolence
In 1990, St. John Paul II issued a clear message to Catholic academia, namely, that a "Catholic University … is called on to become an ever more effective instrument of cultural progress for individuals as well as for society. Included among its research activities, therefore, will be a study of serious contemporary problems in areas such as … the search for peace" (Ex corde Ecclesiae). CNI has taken up this challenge to Catholic universities, by promoting efforts to further develop Catholic social teaching on nonviolence and by introducing tools and resources that advance the shared understanding of active nonviolence and just peace.
The subject has enjoyed some recent momentum. Pope Francis has called the Church to increasingly study peace and in 2018 he created a Sciences of Peace degree at the Lateran University in Rome. Last year, Ken Butigan, a member of the CNI executive committee and faculty member at DePaul University, published "The University's Responsibility for Peace and Nonviolence" in the Vatican's Congregation of Catholic Education journal, Educatio Catholica (vol. 4, 2019). This attention led to CNI making presentations at multiple academic conferences and universities around the world, including in the UK, the Philippines, Kenya, Australia, Japan, Pakistan, and the United States. Committee members also have published numerous books and articles.
CNI also maintains a list of peace studies programs at Catholic universities around the world. In addition, we have developed a catalog of resources for use by educators and parents, organized by student age group. This material and many other resources are available on the CNI website. We would be happy to work with your institution to create an online or in-person event or conference on these topics, as well as training in a range of skills, such as nonviolent communication, bystander intervention, restorative circles, unarmed civilian protection, or nonviolent campaign strategy. The broader CNI action guide includes further resources for universities.
In the apostolic constitution Veritatis Gaudium ("On ecclesiastical universities and faculties"), Pope Francis encouraged a culture of encounter, the encounter with Jesus that promotes dialogue, communication, and communion. Catholic universities are a place for such encounter and communion to be nurtured. In the Winter 2016 issue of this newsletter, Michael Galligan-Stierle wrote: "Catholic colleges have their part to play in this 'field hospital,' helping mend the wounds of a divided society. Now is the time for Catholic higher education to recommit itself to maintaining learning environments in which all people of good will of any political, economic, or religious persuasion can engage in civil discourse in the pursuit of truth."
We invite your help with the mission of the Catholic Nonviolence Initiative. In our institutions of Catholic higher education, let us continue to work together — with faculty, staff, and students — to share the blessings of peace.
Marc Tumeinski, PhD, is assistant professor of Theology and program director of Graduate Theology at Anna Maria College.
This article appeared in the Association of Catholic Colleges and Universities' Summer 2020 Newsletter
For more information on ACCU, please visit their website.
By accepting you will be accessing a service provided by a third-party external to https://www.annamaria.edu/


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Gerald Griffins will look to earn promotion to the Senior Football Championship this Sunday when they face Galtee Gaels in the Intermediate Final.
Speaking ahead of the clash, Gerald Griffins manager John Lynch spoke about how much it would mean to the rural football club to earn promotion to the senior ranks this weekend.
"It's difficult to describe but everyone knows what it would mean to a small place, it's different for a bigger town. But for us we have a GAA club and the whole parish revolves around that."
These sides met in round five of the group stages with Gerald Griffins coming out on top by five points, 0-12 to 0-7.
However, Lynch doesn't feel like that game will have much bearing on this weekend's result with both sides already qualified for the knockout stages when they met in August.
"I don't think it will make any difference. It was over two months ago, different conditions we were both pretty much assured of qualifying. We know how good they are."
Watch the interview with Lynch on our Facebook page below.


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News Releases
October 9, 2019: Man Charged with Kidnapping, Beating Ex-Girlfriend in Arcadia
An Arcadia man has been charged with beating the mother of his two children when she visited his home last month and then preventing her from escaping, the Los Angeles County District Attorney's Office announced today.
Robert Michael Mendez (dob 8/26/92) faces one count each of kidnapping and criminal threats and three counts of injuring a girlfriend or child's parent.
The felony complaint includes an allegation that the defendant inflicted great bodily injury under circumstances involving domestic violence.
Arraignment is scheduled today in Department D of the Los Angeles County Superior Court, Pasadena Branch. Case GA106596 was filed on Oct. 2.
Mendez allegedly assaulted the victim on Sept. 29 at his Arcadia home, prosecutors said. When the victim attempted to escape, the defendant reportedly followed the woman and dragged her back to the home while beating her, prosecutors added.
Deputy District Attorney Lisa Tanner is the assigned prosecutor.
Bail is set at $330,000. Mendez faces a possible maximum sentence of more than 16 years in state prison.
The case remains under investigation by the Arcadia Police Department.


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Top tips for holiday savings
Holidays are a chance to relax, unwind and really indulge but, depending on where and when you travel, they can be expensive. So, how do you save money on holiday essentials in 2015? Here is some advice to help you enjoy your getaway for less and on a budget.
Image by Rob124, shared under a Creative Commons Licence
Book early
There are lots of different elements to the perfect holiday: flights, hotel, currency and clothing to name just a few. While these essentials tend not to cost too much on their own, when they're added together they can cause a significant dent in your holiday budget. To make the biggest saving on your holidays, the answer is to be organised and book everything early.
At Falcon we offer low deposits (where available) on holidays booked more than 8 weeks in advance, which means you can book your dream holiday from just £75 per person. Booking far in advance gives you the chance to pay your full holiday balance bit by bit, with the final payment not being required until 12 weeks before departure.
While it's well known that the cost of flights and accommodation can drop significantly if you book early enough, other factors, such as car hire and currency should also never be left until the last minute. Arrange your car hire when you book your holiday and you will save a noticeable amount of money compared to holidaymakers that book car hire once arriving at their destination.
Similarly, buying holiday currency at the airport – while seemingly more convenient –will cost more compared to buying your currency in advance. Travel money kiosks in airports are notoriously more expensive than other companies and you won't always get the best deal, so buy before you fly and don't leave it to chance.
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Check your phone
Mobile phones have become invaluable when travelling, and thanks to advancements in technology, travel apps, language apps and sat nav apps, such as Navfree – which can be used in over 50 countries – give travellers the ultimate peace of mind when they're exploring their destination.
There are thousands of apps available to travellers and many of them are free to download and use, so, once you know where you're going, start looking at the kind of apps you will need and perhaps you could even learn some of the local lingo and customs too!
We all know that using your mobile phone abroad can be very expensive; but it's not just texts and calls that add up, data usage is also very pricey. So, if you don't want a nasty shock on your mobile phone bill, remember to turn off 3G and data roaming before you fly. Most hotels and resorts offer free WiFi meaning you should be able to access the internet for free.
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Sort out the essentials
If you're travelling within the EU, the European Health Insurance Card (EHIC) is free and entitles you to state-provided healthcare, for a reduced price, or sometimes, even free in European Economic Area (EEA) countries, should you need it. Accessing medical care abroad can be costly, so don't forget to apply for this card.
Additionally, think about other essentials you'll need, such as travel insurance, a travel pillow, food and drink before the flight and organise them before you fly, as buying last minute items in the airport is more expensive.
You can save so much money on your holiday this year, so start looking at what you can do to cut your costs today, your bank balance will thank you.


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Prolyl‐4‐hydroxylase (PHD) inhibitors in clinical trials.
Anemia is a common complication of chronic kidney disease (CKD) associated with disease progression and increased mortality. This anemia is mainly due to inadequate production of erythropoietin (EPO) by the failing kidneys, resulting from the reduction in renal EPO‐producing cells (REPC) or from dysregulation of the hypoxia‐inducible factor (HIF) system that regulates several genes related to hypoxia, angiogenesis, fibrosis and glucose metabolism, among others. In this chapter, we present a review on the HIF system in CKD‐anemia, the HIF response to erythropoiesis‐stimulating agents (ESA) therapy and its potential involvement in the development of ESA resistance by enhancing kidney fibrosis and inflammation. Due to concerns related to ESA use, new drugs to correct anemia are under study, being the prolyl hydroxylase inhibitors the most promising candidates.
- chronic kidney disease
- erythropoietin resistance
- fibrosis
- HIF system
- Hypoxia
- inflammation
1. Introduction
Anemia is a common complication of chronic kidney disease (CKD) that often develops early in the course of the disease, and its frequency and severity increase with the decline of renal function [1]. This condition is associated with a decreased quality of life [2, 3], increased hospitalizations and comorbidities [4, 5], progression of renal dysfunction [6–8], enhanced cardiovascular complications [9, 10] and mortality [11–13]. The main cause for anemia in CKD patients is erythropoietin (EPO) deficit, due to decreased hormone production by the failing kidneys; other factors can also contribute to the development or worsening of CKD‐anemia, such as iron deficiency, inflammation and uremic toxins, among others [14].
EPO is a glycoprotein that presents several functions acting as a hormone, cytokine or growth factor on target cells that express the EPO receptors (EPOR), through different pathways. In the bone marrow, EPO controls cell proliferation, differentiation and death of erythroid cells.
During fetal life, the majority of EPO is produced by the liver; after birth there is a switch to renal production, and in the adulthood, 90% of this hormone is produced by the kidneys, whereas the liver is a secondary site of production [15]. EPO is also expressed in the brain, spleen, lung and testis, but its contribution to serum EPO levels is not clarified [16]. The kidney cells responsible for EPO production are still under debate, but several studies showed that renal EPO‐producing cells (REPC) include the peritubular fibroblast‐like interstitial cells in the inner cortex and in the outer medulla [17, 18], the proximal and distal convoluted tubules and cortical collecting ducts [19]. REPC are sensitive to changes in oxygen (O2) tension, and in conditions of hypoxia, the kidney responds increasing the number of REPC capable of producing EPO [20].
In CKD, the severity of the disease defines the kidney capacity to produce EPO [21, 22]. Indeed, patients with GFR >30 mL/min/1.73 m2 are still able to induce a physiologic response to anemia, showed by the normal or even elevated serum EPO levels [23, 24]. Nevertheless, serum EPO levels may not be sufficient for the degree of anemia; actually, anemic patients with normal renal function may present a 10‐fold to 100‐fold increase in serum EPO levels [25, 26], to achieve correction of anemia.
The kidney is the major site of EPO production in the adults; however, it is possible that extrarenal sites contribute for the marked rise in plasma EPO in end‐stage renal disease (ESRD) patients [27], as already showed in animal models of kidney injury [28, 29]. It was also reported that patients with anemia can switch EPO production from the kidney to the liver [30, 31], as can be shown by glycoform analysis of EPO. Indeed, the posttranslational EPO glycosylation is specific of the synthesizing cells, giving rise to different EPO glycoforms that can be used to localize EPO synthesis [30, 32].
Hypoxia regulates the EPO gene through the hypoxia‐inducible factor (HIF) system [20]. This HIF system includes O2‐dependent HIF‐1α, HIF‐2α (also known as endothelial PAS domain‐containing protein 1) and HIF‐3α subunits, and the constitutively expressed HIF‐1β and HIF‐2β subunits (also known as aryl hydrocarbon receptor nuclear translocator). The HIF‐α subunits are hydroxylated in specific proline residues, by the prolyl‐4‐hydroxylase (PHD) proteins that require O2 as a co‐substrate ( Figure 1 ). The hydroxylated HIF‐α subunit targets the von Hippel‐Lindau tumor suppressor protein (VHL) to be recognized by an ubiquitin ligase complement that will induce a rapid ubiquitination and proteasomal degradation of HIF‐α subunits. Under normoxia, HIF‐α subunits are almost undetectable, but in hypoxic conditions, the hydroxylation by PHD proteins is inhibited; thus, the HIF‐α accumulates in the cytoplasm, is translocated to the nucleus and binds to the HIF‐β subunit, forming a complex that recruits the coactivators P300/CBP and activates the transcription of several genes [20].
Several genes are regulated by the HIF‐1α and HIF‐2α subunits ( Figure 1 ), but recent studies showed that HIF‐2α is the main regulator of EPO synthesis in the kidney and liver [33–35] and is also important for the regulation of several factors involved in iron homeostasis, as iron is an important element for hemoglobin (Hb) synthesis [36]. The HIF‐1α subunit activates the transcription of glucose metabolism, angiogenesis and fibrosis related genes to promote wound healing [37]. The role of HIF‐3α is still ambiguous and under current investigation. It is known that HIF‐3α presents several isoforms with different roles [38]; the up‐regulation of some HIF‐3α isoforms appears to act as a negative feedback mechanism to regulate HIF‐1α and/or HIF‐2α subunits; however, recent studies showed that HIF‐3α might share with HIF‐1α the regulation of some genes [39].
This chapter reviews the HIF response to erythropoiesis‐stimulating agents (ESA) therapy focusing on its potential involvement in the development of ESA resistance, by enhancing kidney fibrosis and inflammation.
2. Hypoxia and progression of renal disease
Renal hypoxia is well known as an important contributor for the progression of renal disease. A study conducted in a rat model of diabetic nephropathy reported that intrarenal hypoxia develops early in the course of the disease and precedes the alterations in circulating biomarkers of kidney damage [40]. Irrespective of the initial cause of CKD, the histopathological analysis of renal biopsies showed that fibrosis is the common final pathway [41]. The underlying mechanisms are still debatable.
Glomerular injury leads to a reduction in glomerular blood flow and consequently limits blood flow into peritubular capillaries, causing hypoxia and tubulointerstitial injury [42]. After an initial injury, the tubular cells will attempt to correct and repair the injury by recruiting and activating several cells, such as macrophages, fibroblasts and epithelial tubular cells that will release pro‐inflammatory cytokines and fibrosis factors, and contribute to excessive interstitial extracellular matrix (ECM) accumulation and expansion. Transforming growth factor beta (TGF‐β), a recognized pro‐fibrotic factor, appears to be central for fibroblast activation, proliferation and transdifferentiation, contributing to ECM deposition [43]. TGF‐β also presents immunomodulatory effects on macrophages and monocyte recruitment, leading to the production of inflammatory cytokines [44]. In early renal injuries, M2‐type macrophages are recruited to promote tissue remodeling; however, if the injury is continuous, more inflammatory monocytes will be recruited differentiating their phenotype into M1‐type macrophages, responsible for the release of pro‐inflammatory cytokines (such as tumor necrosis factor [TNF‐α], interferon [IFN]‐γ, interleukin (IL)‐1β and IL‐6) and cell apoptosis [45]. The release of these pro‐inflammatory cytokines leads to the activation of the nuclear factor kappa B (NF‐κB) pathway, thus amplifying the inflammatory process [44]. The continuous activation of this system will culminate with the formation of scar tissue or fibrosis. The presence of fibrotic tissue reduces the diffusion of O2, which will further aggravate the hypoxic environment.
Anemia caused by inadequate EPO production by the kidneys also contributes to renal hypoxia. However, the mechanisms underlying the reduced capacity for EPO production by the REPC are not well understood. It has been proposed that after renal injury, REPC can suffer a transdifferentiation, called epithelial to mesenchymal transition (EMT), into myofibroblasts, losing their capacity to synthesize EPO and increasing the synthesis of collagen, contributing to the expansion of ECM [46]. Nevertheless, this EMT phenomenon was never proved in humans. The residual capacity to increase serum EPO levels when subjected to hypoxic environment or high altitudes by renal patients, even those on dialysis [47], indicates that a dysregulation of the HIF system, more than a complete loss of REPC cells, could be responsible for the reduced EPO production. Moreover, the pharmacological inhibition of the PHD in CKD patients stimulates endogenous EPO production further supporting a deranged oxygen sensing [27]. A recent study in mice by Souma et al. [48] also strengthened this hypothesis, by showing that inflammatory cytokines and/or fibrosis factors suppress HIF activation through the over‐activation of PHD even under pathologic hypoxic conditions, and that the inhibition of PHD restores EPO production.
3. Erythropoiesis‐stimulating agents in CKD‐anemia
The standard treatment for CKD‐anemia is based on pharmacological intervention, using ESA and/or iron supplementation, in order to correct and maintain Hb concentration in the range of 10–11.5 g/dL [49]. ESA are medicines produced by recombinant DNA technology with similar structure and biological activity of EPO. They differ from EPO by the different patterns of glycosylation that increases their half‐life.
The use of ESA has beneficial effects by correcting anemia and their associated symptoms and improving patients' quality of life [50, 51]. However, the effects of ESA on the progression of renal function are controversial. Some studies showed that after starting ESA therapy and correction of anemia, renal function declines at a slower rate, delaying the need for dialysis in pre‐dialysis patients [52–54]; in opposition, other studies reported that ESA do not significantly affect renal function [55, 56].
ESA were designed to correct anemia, but some evidences showed that these drugs (and EPO) may act beyond hematopoiesis. Pleiotropic effects have been attributed to EPO and ESA, such as cytoprotection, anti‐apoptosis, anti‐inflammatory and angiogenesis [57]. These non‐hematopoietic actions appear to result from the activation of another EPOR, a heterodimeric receptor constituted by the EPOR homodimer complexed with CD131, the common beta receptor (βCR) that is involved in granulocyte macrophage colony‐stimulating factor, IL‐3 and IL‐5 signaling [58]. The two EPOR present different affinities for EPO; in erythroid cells picomolar concentrations of EPO are sufficient to trigger activation of the EPOR homodimer, whereas on other cells and tissues high local EPO concentrations are needed to activate EPOR heterodimer [59]. This receptor was detected in several cells and tissues, such as brain (neurons, astrocytes and microglia), kidney, female reproductive system organs, vascular endothelial cells, cardiomyocytes, lymphocytes and monocytes, among others [57].
The slower progression of renal dysfunction observed in some CKD patients may result from renoprotection of ESA therapy. Several studies on acute kidney injury (AKI) reported that a single dose of recombinant human EPO (rHuEPO) reduces kidney dysfunction through anti‐apoptotic mechanisms and increases NO production, only in intact vessels [60]. ESA therapy also exerts renoprotective effects by reducing the production of pro‐inflammatory cytokines (e.g., IL‐1β and TNF‐α), acute phase proteins [e.g., C‐reactive protein (CRP)], pro‐fibrotic factors (e.g., TGF‐β) and oxidative stress [61]. However, these effects appear to be only achieved with low doses of ESA, as high doses increase hematocrit and may activate platelets, increasing their adhesion to the injured endothelium, contributing to hemorheologic changes [60]. Indeed, other side effects are associated with ESA therapy, namely hypertension [62] and thrombotic events [63].
Despite the benefits of ESA therapy, some concerns have emerged from studies reporting a high incidence of cardiovascular events and mortality in CKD patients treated with ESA [63, 64], independently of the type of ESA used [65, 66]. Since the introduction of ESA therapy, several clinical trials aimed to define the better Hb target/ESA dose associated with lower cardiovascular risk. Indeed, recent studies reported increased cardiovascular risk and death in patients treated with high ESA doses to achieve higher Hb levels [9, 67–69].
The need for new drugs with lower associated cardiovascular risk opened a growing area of research. The most promising are the PHD inhibitors ( Table 1 ) with several compounds already under evaluation in clinical trials. Some of these compounds showed to be well tolerated, corrected anemia in non‐dialysis CKD and incident dialysis patients without increasing blood pressure, and also reduced serum hepcidin levels [70–73]. However, regarding their effects in reducing cardiovascular events and slowing the progression of the renal disease, no data are still available from human studies. Yu et al. [22] showed that the administration of PHD inhibitors in a more advanced stage of CKD in the rat reduced renal fibrosis and protected renal function, whereas the administration in an early stage of CKD promoted renal fibrosis and exacerbated renal dysfunction. In another strategy to induce EPO production, the hydrodynamic gene transfer of a plasmid encoding for EPO in a rat model overexpressing TGF‐β showed that this therapy increased Hb levels but had no effect on kidney fibrosis or function [74].
|PHD inhibitor
|Route administration
|ClinicalTrials.gov Identifier
4. Hyporesponsiveness to erythropoiesis‐stimulating agents in CKD
The majority of CKD patients respond adequately to the currently available ESA therapy, but 5–10% of them do not respond properly, developing hyporesponsiveness to these drugs [75]. According to the KDIGO guidelines [49], CKD patients can present initial or acquired ESA hyporesponsiveness; in primary hyporesponsiveness patients, after one month of treatment with adequate weight‐based ESA dose, the target Hb concentration is not achieved; in acquired ESA hyporesponsiveness, after effective treatment with stable ESA dose, achieving the target Hb concentration, the patient requires two consecutive increases (up to 50% beyond the stable dose) in ESA dose. Hyporesponsiveness (also widely referred as resistance) to ESA therapy is associated with a poor outcome, progression of renal disease, sudden death, infectious complications, sudden death and all‐cause mortality, mainly due to cardiovascular events in dialysis patients [76–79]. Several causes are associated with poor response to ESA therapy, including iron deficiency, inflammation, malnutrition and hyperparathyroidism, among others [80–82].
4.1. Inflammation
A pro‐inflammatory state is a hallmark of CKD, which is due to increased uremic toxins that induce the production of inflammatory cytokines. Additionally, active infections, the vascular access for hemodialysis (HD) procedure and surgery‐related inflammation (vascular surgery included) can also contribute to inflammation.
The activation of inflammatory cells is also associated with increased oxidative stress, favoring alterations in red blood cells (RBC) membrane, namely increased phosphatidylserine exposure, increased membrane bound Hb and increased membrane protein band 3 aggregation, all markers for RBC phagocytosis by macrophages and, thus, for a premature RBC removal [83, 84]. Uremic toxins and pro‐inflammatory cytokines also inhibit erythropoiesis, through the inhibitory effect of IL‐1β, TNF‐α and IFN‐γ on early erythroid cell stages in the bone marrow [85]. The macrophages of the bone marrow can also be stimulated to increase local pro‐inflammatory cytokines, amplifying the effects of systemic inflammation [86]. In CKD patients, hepcidin synthesis is enhanced, due to the increase in Il‐6, contributing for the limited iron availability for erythropoiesis [87]. Indeed, CKD patients often present with replete or even higher iron stores, alongside with inflammation and anemia. A disturbance in the crosstalk between inflammation, iron metabolism and erythropoiesis may, therefore, favor ESA hyporesponsiveness. The best predictors for ESA response appear to be IL‐6 and CRP [88, 89]. Studies conducted by our group showed that HD patients with poorer response to ESA present higher levels of pro‐inflammatory cytokines [90, 91]; moreover, in studies using a rat model of chronic renal failure, we found that the severity of the inflammatory state was related to the reduction in the rHuEPO response [92].
4.2. HIF system in the hyporesponsiveness to erythropoiesis‐stimulating agents
Hyporesponsive patients to ESA therapy will develop anemia, and as already referred, it will promote the progression of renal disease. Tissue hypoxia is amplified according to the severity of anemia that will reduce O2 availability to body tissues and organs. Within the kidney, the hypoxic environment leads to the activation of the HIF system, promoting the transcription of several target genes. In the hypoxic kidney, HIF‐1α is essentially expressed in tubular and glomerular epithelial cells, whereas HIF‐2α expression is limited to endothelial and interstitial cells [93]. The localization of these HIF‐α subunits is related to their target genes.
Renal biopsies from CKD patients showed that increased expression of HIF‐1α in tubular epithelial cells is correlated with the stage of renal disease [94]. It was reported that HIF‐α activation in CKD rats presents dynamic changes, as it is activated in early CKD stages and suppressed in the moderate and end‐stage of CKD [95]. Thus, the administration of PHD inhibitors may improve renal function in more advanced stages of CKD, while in earlier stages, the PHD inhibitors may increase renal fibrosis due to upregulation of the HIF‐1α subunit [22].
HIF‐1α subunit is involved in the activation of pro‐fibrotic genes ( Figure 1 ), including the connective tissue growth factor (CTGF) gene [96]; indeed, the plasma levels of CTGF appear as a good marker for staging diabetic nephropathy progression [97]. CTGF is a potent pro‐fibrotic factor and a marker of renal fibrosis, increasing ECM production, promoting EMT, stimulating fibroblasts and potentiating TGF‐β signaling [94, 98]. CTGF and TGF‐β present similar effects, but TGF‐β also presents immunomodulatory actions [44], recruiting macrophages to reduce the injury; however, a continuous macrophage activation leads to excessive ECM accumulation and increased release of pro‐inflammatory cytokines promoting fibrosis. A study by Basu et al. [99] suggested that TGF‐β can in turn induce HIF‐1α activation, which would amplify cell collagen expression contributing to the progression of fibrosis.
There is also a crosstalk between HIF‐1α and inflammation ( Figure 1 ). Inflammation favor tissue hypoxia by several mechanisms including: impaired EPO response, iron mobilization and bone marrow erythropoiesis, reduced RBC lifespan and also increased demand for O2 by the inflammatory cells in order to increase pro‐inflammatory cytokines. However, it was also reported that NF‐κB can induce HIF‐1α activation due to the presence of responsive elements in the promoter of HIF‐1α gene [100]. Another mechanism is the interaction of PHD with some effectors of the NF‐κB pathway, though the exact proteins involved remain unknown [101].
The majority of the studies report a beneficial effect of ESA on renal fibrosis through several mechanisms [29, 102]. However, recently Gobe et al. [103] reported that in rat model of AKI the use of higher rHuEPO doses was associated with increased TGF‐β expression, oxidative stress and stimulation of fibroblasts and EMT, contributing to the progression of the disease and gradual development of CKD in the long term. In this study, the expression of HIF‐α subunits was not reported, as well as the linking between HIF activation and the alterations observed. Further studies regarding this issue are warranted.
Despite the underlying mechanism, a continuous inflammatory response favoring fibrosis and a disturbance in the HIF system creates a vicious cycle, contributing to the progression of renal disease and aggravation of renal anemia [92], and reducing the response to ESA therapy creating a scenario of hyporesponsiveness to EPO.
5. Conclusions
Anemia is a common complication in CKD patients that can be corrected by the treatment with ESA. However, the development of a hyporesponse to this therapy was associated with (i) the progression of the renal disease, due to the amplification of fibrosis and inflammation through a mechanism involving activation of HIF‐1α pathway; (ii) increased risks in the development of cardiovascular disorder events and all‐cause mortality in patients treated with higher doses, opened a new research field, focused on the design of more effective agents to control anemia in CKD patients, with less side effects. The use of PHD inhibitors is promising, but further is needed to confirm their effects in the reduction of cardiovascular events and progression of renal disease.
This work received financial support from FCT/MEC through national funds and co‐financed by FEDER, under the Partnership Agreement PT2020 (UID/MULTI/04378/2013—POCI/01/0145/FERDER/007728, UID/NEU/04539/2013) and Norte Portugal Regional Coordination and Development Commission (CCDR‐N)/NORTE2020/Portugal 2020 (Norte‐01‐0145‐FEDER‐000024).