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Everest High Passes and Island Peak:
Trekking Days : 20 Days. Kathmandu Stay : 04 Days. Departure Day: 01 Day.
Everest High Passes and Island PeakUS$ 2650 USD
OUT LINE ITINERARY
PACKAGE INCLUDES & PACKAGE EXCLUDE
Everest High Passes and Island Peak:
The number of days required for Everest High Passes and Island Peak will be dispersed as:
Renjo Pass, Chola Pass, and Island Peak:
Trekking Days: 20 Days.
Kathmandu Stay: 04 Days.
Departure Day: 01 Day.
Everest High Passes and Island Peak is unquestionably an ideal pick for a true adventure seeker who is in the quest for a genuine venture and looking for a challenging trek to unleash their outdoor curiosity. However, this 21 days expedition through 2 high passes, Renjo Pass (5360 m/17,585 ft) and Chola pass (5,420 m/17,782 ft) is more of a secretive trek. It takes you deep into the untouched magnanimous lofty valleys that give anyone genuine wilderness experience.
Furthermore, it delivers off-the-beaten-track experience away from the substantial flooding of tourism like in the major trails of Everest. Going over these high altitude passes is undeniably very challenging but very worthwhile with its exceptional beauty. Moreover, the accomplishment of being at the top of them is very appealing. It certainly gives anyone more of a chance to know, understands, believes and trusts yourself. Everest High Passes and Island Peak expedition transfers you to the interestingly challenging magnanimous high passes with the most splendid and unbelievable views.
Island Peak Expedition:
Island peak climbing offers anyone with exhilarating climbing experience with its challenges and breathtaking views from the summit. The Island Peak (6189 m / 20,305 ft) was named in 1951 by Eric Shipton, a distinguished British Mountaineer and was renamed as Imja Tse in 1983. Here the cook takes accountability for all the diverse meals and. They are the professionals and highly trained in hygiene, meal variety, and presentation. They are masters at preparing selections of food under less than ideal conditions.
Our accomplished climbing Sherpa will conduct a clinical course on required climbing skills and safety measures. Island peak has always served as a preparation arena for mountaineers before scaling any high peaks. Our itinerary is so designed that we have enough time for healthier adaptation to the thin air environment that exists in the Everest region. This acclimatization policy could eventually guarantee everyone a safe passage to where we are going. Though Everest high passes and Island peak is physically demanding yet its beauty cannot be denied.
To make your peak-climbing trouble-free we resource you with the entire facility of issuing permits, organizing equipment to finding reliable climbing Sherpas. Worrying is out of the question since we are here to craft your dream of climbing experience.
Short Itinerary DAY 01:Arrive to Kathmandu (1,400 m/4,593 ft) DAY 02:Half day city tour/ afternoon trek briefing and preparation / welcome dinner DAY 03:Fly to Lukla (2,840 m/9,317 ft) and trek to Phakding (2,610 m/8,562 ft) DAY 04:Trek to Namche (3,450 m/11,318 ft) DAY 05:Acclimatization day at Namche /morning excursion. DAY 06:Trek to Thame (3,820 m/12,532 ft) DAY 07:Trek to Lungden (4,368 m/14,338 ft) DAY 08:Acclimatization day at Lungden /morning excursion. DAY 09:Trek to Gokyo (4,790 m/15,715 ft) via Renjo Pass (5,360 m/17,585 ft) DAY 10:Rest day at Gokyo DAY 11:Trek to Dragnak (4,700 m/15,419 ft) DAY 02:Trek to Dzongla (4,830 m/15,846 ft) via Chola Pass (5,420 m/17,782 ft) DAY 13:Trek to Lobuche (4,910 m/16,108 ft) DAY 14:Trek to Gorakshep (5,189 m/17,024 ft) and trek to Everest base camp. DAY 15:Morning excursion to Kalapathar (5,545 m/18,192 ft) Trek to Dingboche (4,350 m/14,271 ft) DAY 16:Trek to Island Peak Base camp (5,200 m/17,060 ft) DAY 17:Rest Day + Clinical course by the Climbing Sherpa. DAY 18:Mid night wake up and set off for Summit (6,189 m/20,305 ft) DAY 19:Extra day in case of any weather circumstances. DAY 20:Trek to Pangbuche (3,930 m/12,893 ft) DAY 21:Trek to Namche DAY 22:Trek to Lukla DAY 23:Fly to Kathmandu DAY 24:Contingency day in Kathmandu in case of flight cancellation. DAY 25:Departure day.
The above itinerary is simply a guideline and is subject to alteration as per the circumstances. Your group leader is solely liable to bring about changes in the best interest of the group. Flight Delay/Cancellation in Kathmandu and Lukla:
The unpredictability of Flights flying to and from Lukla airport, the gateway to Mount Everest and the world’s most electrifying airport is pretty evident from its history of delays and cancellation. Diverse factors lead to the situation of cancellation including the weather, technical issues, poor visibility, etc. In such conditions, Ultimate Nepal Adventure will charter a helicopter to make certain that you don’t miss your trip or your international flight. But again under these circumstances, the possibility of flying helicopter depends on the Nepal Civil Aviation flying rules.
Travelers are to pay the cost of the chartered helicopter which is payable through cash, traveler’s cheques, or credit cards (Visa and Master Cards only). Travelers will be provided with receipt upon payment so that they may claim the amount from their travel insurance. The cost per person is governed by the number of people taking this facility.
Why extra night in Kathmandu???
After the trip, travelers have one additional leisure day in Kathmandu, the living heritage city, which in reality is a contingency day in case of Lukla – Kathmandu flight cancellation under certain circumstances. This certainly gives anyone more of a chance to explore Kathmandu, the capital, ‘The Shining Pearl of Asia’ with its beautiful temples, monuments and time-honored legends and history. Ultimate Nepal Adventure will always be there to assist you with your city exploration.
Detailed Itinerary DAY 1: KATHMANDU, THE CAPITAL CITY (1,400 m/4,593 ft)
Soon you land in Kathmandu airport your group leader will be there with Ultimate Nepal adventure board to greet you and transfer you to the hotel. Despite, the capital city of Nepal certainly being the busiest with hectic traffic it undoubtedly has a strong appeal with local splendor and vigorous activities around, where you can simply relax and take pleasure in the fun of driving through the unfamiliar roads.
• Pick up from the international airport.
• Transfer to the hotel by your Group Leader.
• Short preliminary briefing.
• Arriving early allows you to explore Kathmandu.
• Welcome dinner and getting to know each other.
DAY 2: IN KATHMANDU
Today would be the most exhilarating day where your leader introduces you to our city tour expert who guides you to the most pious Hindu and Buddhist religious place that is listed in the world heritage sites and elucidates you the entire mysticism over its existence.
• Breakfast depending on your choice and preference.
• Meet-up at 9 is for the tour.
• Visit Boudhanath Stupa and Pashupatinath.
• Lunch on your preference.
• Getting together for trek briefing as per the time given by your leader.
• Distribution of the company’s trek equipment’s.
DAY 03: FLIGHT TO LUKLA (2,800 m / 9,186 ft) TREK TO PHAKDING (2600m/8530ft) 3/4hrs
This 3/4 hours easy walk on the legendary trekking trail through the cultured Sherpa villages with its exceptional beauty and the view of stunning landscape, deep valley and Dudh Koshi gorge is unique.
• Flying in a twin-otter plane to a small Lukla airport at the elevation of 2840m
• A beautiful walk through the series of stunning native settlement
• The phenomenal sight of profound gorges, ancient farming terraces and the scenic beauty at the backdrop is something special on the very first day.
• Overnight stay at stunning Phakding, fabulous dinner and briefing by your leader along with several fascinating stories.
DAY 04 – 05: TREK TO NAMCHE BAZAAR (3,450 m / 11,318 ft) 7 hrs. ACCLIMATIZATION DAY
Today we will start early for Namche Bazaar, the capital and the Administrative Center of the Khumbu district. It’s more of a luxurious city in the middle of no way in remoteness and thin air. Despite long hours walk it’s far more than just trekking. Give time to adapt your body with thin air. It’s not a matter about proving your physical strength, its more about taking pleasure with steady ascend.
• Wake up call as set by your leader
• 3 hours gentle walkthrough series of pleasant villages to the last settlement of Jorsale for lunch
• The crossing of 5 high suspension bridges is daring.
• The scenic beauty, deep gorges of soaring cliffs at the backdrop is phenomenal.
• Being at Namche, the dreamland is remarkable which is worth an effort.
• 1 and ½ hours amazing walk for acclimatization.
• Walk to Syangbuche, one of the enchanting places in the region with the world’s highest airstrip.
• Visiting Everest View Lodge with an incredible view and hot beverage.
• The close view of the magnificent mountain, extensive green hills, the Tibetan Buddhist culture and to witness the territory of the yaks is charismatic
• The first view of the world’s highest mountain (Mt. Everest)
DAY 06: TREK TO THAME (3,820 m/12,532 ft) 5hrs.
Today we will leave the crowded Everest route and follow the amazing Bhote-Koshi valley to the exceptionally sensational village of Thame, the ancient salt trading route between Tibet and Nepal. A moderate 4 and ½ hours walk will get us to the village of Thame which is said to be the home of inherent climbers from Tenzing Norgay Sherpa (first Everest summiteer) to Appa Sherpa (who holds the Guinness book of world record). This exquisite hidden valley is indeed very enchanting.
• 5 hours of easy walk
• Getting to Thame, the home village of Tenzin Norgay Sherpa.
• Afternoon visit to ancient Thame Dechen Chokhorling Monastery.
DAY 07 and 08: TREK TO LUNDEN (4,368 m/14,338 ft) 5/6 hrs AND ACCLIMATIZATION DAY:
A gradual ascent following the Bhotekoshi River through the ancient salt trade route will eventually take you to the very small settlement of ‘Lungden’ The Base of Renjo La. Since you are getting more into an alpine area, the slow ascent is recommended. This unfamiliar and very untouched hidden valley is charismatic where you will have a rest day to explore more of it.
• Remarkable walk to the untouched valley of Lungden.
• Being above the tree line and seeing very few people gives you the Thrill of being at altitude.
• We can admire the traditional architecture walking through the less-traveled villages.
• Approximately 3 hours walk for acclimatization, getting yourself prepared for the next big day.
• Amazing view of different mountains
• Seeing the Yaks graze around you in the wilderness is awesome.
• Free afternoon
• Evening brief from your Leader.
DAY 09 and 10: TREK TO GOKYO (4,790 m/15,715 ft) VIA RENJO PASS (5,360 m/17,585 ft) 8/10 hrs
We wake up pretty early this morning for a challenging 5-hour climb to the top of Renjo Lha “ A stunning pass from where one can see three 8000+ mountains including Mt. Everest and its neighboring peaks” Followed by 3 hour downhill to Gokyo. After the accomplishment, the view of sparkling sacred lakes along with the Great view of Cho-Oyu is more than enough to spend another day at miraculous Gokyo.
• Early wake up for the most incredible Renjo Pass.
• The Thrill of being in the wilderness and at altitude can be experienced in the Hard 5 hours uphill and 3 hours of steep downhill with very few people around.
• Spectacular view of mountains along with the Ngozumpa glacier (longest glacier in the Himalayas) and Gokyo Lake from the top of Renjo La.
• Pack lunch ( Normally eaten at the top of Renjo La)
• The excursion is optional if you wish to climb Gokyo Ri or simply want to relish.
• Free afternoon
DAY 11: TREK TO DRAGNAK (4,700 m/15,419 ft) 3 hrs
Easy 3 hours walk through the Ngozumpa Glacierm, the longest glacier in the Himalayas to Dragnak, the base of our second pass Cho La. Dragnak, a small settlement is very secluded but very lively.
• It’s a thrilling experience to get across the Ngozumba glacier with the sounds of ice cracking, river flowing and rocks rolling in the glacier.
• View of small glacial lakes around.
• Good view of Mt Cho Oyu from the glacier.
• Be cautious about the rockfall zone.
• Free afternoon
Day 12: TREK TO DZONGLA (4,830 m/15,846 ft) VIA CHOLA PASS (5,420 m/17,782 ft)
Another early wake up for a challenging 5-hour climb to the top of Chola Pass, the exquisite glacial pass. Today you would walk into yet another very untouched alpine valley with the mysterious landscape setting. After the accomplishment, we have 3 hours of technical descent through the rock face trail to Dzongla. Dzongla with an unbelievable view of Cholatse at the backdrop is sensational.
• Early wake up for another incredible Chola Pass.
• Scrambling skills will be required for the glacier moraine to get over and below the pass.
• Close up mountains view all around.
• The walk across the icy glacier is sensational.
• Basic crampon recommended for the pass.
• Great view of Amadablam, Cholatse and many more mountains on the way down.
DAY 13: TREK TO LOBUCHE (4,910 m/16,108 ft)
It’s time to get back into the bustling zone of the regular Everest base camp trail. An easy enchanting 3 hours walk with the most intriguing panoramic view is overwhelming.
• Amazing view of Nuptse, Pumori, Amadablam, Cholatse and many others along the way.
• Back into the main route to Everest base camp.
• Free afternoon.
DAY 14: TREK TO GORAK SHEP (5,288 m /17,349 ft) 3 hrs / TREK TO EVEREST BASE CAMP (5,360 m/17,585 ft) 5 hrs
Leaving Lobuche this 3 hours walk to Gorak Shep is out of the ordinary through the rocky moraine undulating trail. Gorak Shep, the spectacular village is surrounded by Pumari (7145 m), Lingtren (6697 m), Nuptse (7745 m) and of course Everest (8848 m).
• Spectacular view of the Khumbu icefall with soaring mountain
• Trek to fascinating Everest base camp after lunch
• View of the base camp and the blue ice pinnacles of the icefall is astonishing
• Challenging but very rewarding walk to the fro from the base camp
DAY 15: MORNING WALK TO KALAPATTHAR (5,545 m /18,192 ft) 4 hrs AND TREK TO DINGBUCHE (4360m / 14304ft) 4 – 5 hrs
Now is the time for the epic climb to Kalapathar, the point to value your dream and the sensational Himalayan vistas all around. The climb is challenging but the view from the top surpasses the wildest imagination. After making historic success to Everest Base Camp and Kalapattar, we will descend to Dingboche descending at least 1000 m below.
• Phenomenal sunrise view
• A very rewarding moment being at 5545 m with an exceptional panoramic mountain view.
• Overnight at Dingboche, which is way tranquil being away from all the hardship and the thin air.
• Much relaxed after descending 1,000 m of elevation.
DAY 16: TREK TO ISLAND PEAK BASE CAMP (5,000 m/16,404 ft) 5 hrs
We set out early this morning after breakfast for Island peak base camp through the epic trail along the Imja River. We walk along the ridges of moraines and beautiful valley with the view of deep gorges and soaring Lhotse at the backdrop. Beautiful accommodation at the tented camp.
• Moderate walk to Chhukung through imja valley
• Get to see wild sea-buckthorn growing all around.
• Pleasant walk into the Imja valley with grandiose views.
• It’s quite amazing to see all the lively activities at the Base Camp.
DAY 17: REST DAY + CLINICAL COURSE BY THE CLIMBING SHERPA.
Today it’s more of a relaxing day with morning breakfast in a tented dining hall in the enchanting land setting of island peak base camp. Later after breakfast, we gear up for your clinical course, a pre-climbing training that will be conducted by our professional climbing guide. The course includes the proper use of equipment, safety measures, etc. Early dinner as you will be starting around midnight for the summit.
• Waking up in an isolated yet very lively island peak base camp is remarkable.
• Fun time with all the climbing techniques and clinical course conducted by your climbing leader.
• Free afternoon to explore the tented town of Island peak
• Early dinner as the wakeup call is set around midnight for the Island peak summit.
DAY 18: MIDNIGHT WAKE-UP AND SUMMIT (6,189 m/20,305 ft) 10 – 12 hrs
Everyone will be waking up at midnight and soon after we are done with the quick breakfast we set out into the darkness into the unfamiliar path with our headlamps. It’s very marvelous to see the line of lights following the mountain trail that goes high up into the horizon seems like touching the night sky. We ascend with a very gradual pace through the vertical rocky gully that eventually lands us into the Crampon Point where we fix our climbing equipment and set off into the icy trail with crevasses for the Island Peak summit.
• Waking up early and walking in darkness following the lights and foot of others is very adventurous.
• Challenging walk into the rocky gullies with no established trail is daring.
• Going over a few open Crevasses is something very exciting.
• In the summit, great sense of accomplishment with grandiose unbelievable panoramic view.
• Celebration with a cake prepared by our cook of limited or no resources.
DAY 19: EXTRA DAY IN CASE OF ANY WEATHER CIRCUMSTANCES.
This is a contingency day for the Island Peak summit in case of cancellation out of any circumstances, particularly bad weather.
DAY 20: TREK TO PANGBUCHE (3,930 m/12,893 ft) 4/5 hrs
With the great feeling of accomplishment, we will stroll our way down to a beautiful Sherpa settlement of Pangboche. Start breathing normally again since you are in a tree line area.
• A moderate day
• Back in the tree line
• Getting back to normal away from the thin air after a long time is wonderful.
DAY 21: TREK TO NAMCHE 6 -7 hrs.
We retrace our steps back to Namche getting ourselves back to the tree line area where you would realize your breathing getting back to normal. It’s pretty wonderful looking back on our effort to the incredible Island Peak from the Tyengbuche ridge. Visiting the Tyengbuche monastery and walk to Namche on a fresh route makes anyone cheerful of their accomplishment.
• Effortless walk to Tyengbuche monastery, the most active monastery in the Everest region.
• Visit the monastery and lighting the butter lamp is an incredible experience
• Witness the untold history and the activities of Tyengbuche
• Give yourself a break at Namche either with drinks or buying souvenirs.
DAY 22: TREK TO LUKLA
Being it last night fun activities follows with dancing, eating, drinking and tipping.
Day 23 – 24: FLY TO KATHMANDU AND CONTINGENCY DAY
Sensational flight back to the capital city of Kathmandu. You have a contingency day in Kathmandu in case of Lukla-Kathmandu flight cancellation which can be appropriately exploited exploring around the city that has so much to offer.
• Morning flight to Kathmandu
• Explore the Capital City of Kathmandu as per your requirements
DAY 25: DEPARTURE DAY
Depending on your flight schedule airport transportation will be provided. Your leader will be there to send you off home.
Highlights 35 minutes flight to exceptional Lukla airport and walking into the deep valley of traditional Sherpa village is very peaceful and sincerely spectacular.
Walk to Phakding, Namche Bazaar, the valley of Thame and Lungden is one cherishing moment endowed with spectacular panoramic mountains view.
Going over the Renjo pass that has to offer one of the most spectacular views of the panoramic mountain range along with the Ariel view of the lakes is indescribable. In one word, overall it’s inconceivable.
Gokyo with its turquoise blue lakes are exceptionally gorgeous that gives you an alternative to witness an entirely different face of the Everest region which is beyond belief.
Crossing the Gozumpa Glacier, the largest glacier in the Himalayas has a novel magnificence that is always cherished by every single traveler who has dared to undertake it.
Going over the icy Chola Pass is distinct on its own. Being at Dzongla is utterly out of the world; it’s more like being on a different planet with soaring peaks around and a small cozy town in the middle of nothing.
After the successful ascent of Everest Base Camp, 5360 m and Kalapathar, 5545 m the trail now leads you to the different valley offering you with unique features in views and landscapes.
Trek to Island Peak Base Camp is a different experience that offers you a handsome opportunity to walk through the outstanding valley of Imja.
Camping food is what anyone would need in this situation.
Midnight wakeup call and eventually summiting Island peak with exquisite scenic beauty is a great accomplishment of a lifetime where you would realize why Eric Shipton named it as Island Peak in 1951.
Finally, we bid farewell to our island peak base camp crew and trace back to Lukla and flying in a small twin-otter plane back to Kathmandu is breathtaking leaving you with so much contentment and appreciation.
Cost Includes National park entry fees, conservation fees, trekking permit, TIMS permit. Island peak expedition permit. Airport pickups and drops facility on both Domestic and International flights. Three-star twin bed sharing hotel Accommodation in Kathmandu on Bed / Breakfast basis. Half-day guided city sightseeing with paid entrance fee. All Government and Local tax. domestic flights from Kathmandu / Lukla and Lukla / Kathmandu. Fundamental trekking gears like a sleeping bag, down jacket fleece liner, etc. Tea-house accommodation or tented camp as per the trek. Properly boiled water for drinking every evening and morning. Meals (Lunch, dinner, breakfast with hot beverages) during the trek. Two member Tent facility and Kitchen crew at Island Peak base camp with hot meals. An accomplished trekking Group Leader and assistant guides. An accomplished climbing guide. Staff insurance. All climbing equipment’s including climbing boots. Oxygen cylinders and an all-inclusive medical kit on all trips. Take away Ultimate Nepal Adventure duffel bag, T-shirt, Buff (multifunctional head-wear) and trekking Map. Porter service. Porters’ Clothing.
Cost Excludes The fee levied on a Nepali visa. All personal expenses including Food while in Kathmandu. International flight fares. A medical examination or emergency rescues. Donations. Staff Tipping. Extra night accommodation in Kathmandu on early arrival. Travel or medical insurance. Optional tours and sightseeing or any activities during free time. Other personal expenses – laundry, battery charges, shower, etc.
Cancellation for this product is free up to 48 hours before the chosen start date - full refund will be given.If cancelling less than 48 hours before the chosen start date no refund applies.


The Apple Watch is now official!
Apple today goes haywire today with its announcement of “Apple watch”. Apple watch is its first kind from Apple’s family in the world of wearable technologies. Along with the iPhone 6 launch event this morning, Apple released its first smartwatch “Apple watch”. Smartwatch with inductive charging, square face, sapphire glass, swappable bands, a heartbeat sensor and rotating digital crown.
Apple watch allows it users to choose between six different straps, which includes a sport band, a leather loop, a classic leather buckle and a stainless steel strap that is easily adjustable to fit the needs of Apple users.
Apple Watch Versions:
The Apple watch will come in two different sizes with three different versions: Watch, Watch sport and Watch edition.
Prices start at $349 and the Apple Watch will be available “early next year.”
“We love to make new products that improve people’s lives. We love to make things that allow our users to make things that they could never have imagined,” Apple CEO Tim Cook said today. “We think it will redefine what people expect from its category.” He called it “the next chapter in Apple’s story.”
The best feature in the smartwatch is its digital crown with IR and LED diodes. Pressing the dial will take you to the watch’s home screen, were users can personalize the home screen just like your iPhone.
The interface makes full use of the digital crown and developers will be able to use it for their own apps, too. Just like Google’s Android Wear watches, the watch will also be using voice input through Siri.
In addition, Apple developed something it calls “digital touch” to allow you to quickly share a sketch you draw on the watch face. Given that the watch doesn’t have a keyboard, these sketches allow you to still communicate relatively complex ideas easily.
The dial also understands the difference between a simple touch and a press, and the watch will offer at least some haptic feedback.It’s called the Taptic Engine.
Taptic engine is a linear actuator inside Apple Watch that produces haptic feedback. In less technical terms, it taps you on the wrist. Whenever you receive an alert or notification, or perform a function like turning the Digital Crown or pressing down on the display, you feel a tactile sensation that’s recognizably different for each kind of interaction. The Taptic Engine creates a discreet, sophisticated experience by engaging more of your senses.
The Apple Watch will use inductive charging.
The inductive charging is the best feature of Apple watch. It is a sealed system and it is free of exposed contacts. There is no need of precise alignment to charge your watch. You just hold the connector near the back of watch, where magnets can will help the connector to snap into the place automatically.
Apple Watch Fitness Applications:
Apple itself has developed two different fitness apps for the watch, too. The “Activity” app is meant to track your movement throughout the day. The “Workout” app, on the other hand, focuses on specific sports.
Innovation in watching your photos:
Apple also built a cool way to see your photos. You start out all the way zoomed out with all of your photos showing as minuscule thumbnails. Then you use the crown to zoom in. The watch uses the same gesture to move zoom in and out of Apple Maps, too. When it comes to display, A Retina display is the primary surface for every interaction that we make with the Apple watch. The display is laminated to a machined and polished single crystal of sapphire, which is next to diamond, which is the hardest transparent material.
After the release, some of the rumoured features like Curved display, NFC support were remained as just rumours. You can compare the Apple iWatch concepts with the original release of Apple iWatch as “Apple Watch”.


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Having a goldfish requires more effort and care than you think. Sorry, but you can’t just put your little goldfish into a plastic bowl and sprinkle flakes of fish food once or twice a day. Like every other fish, goldfish require extra attention and care in order to be in perfect health.
You may get your goldfish in a clear plastic bag by winning a game at the carnival fair or at a pet store in a small plastic container, but taking great care of it will ensure it’ll live a happy and fulfilled life.
Step 1: Finding The Perfect Home
Using a bowl provides very little space for your fish to swim around if you opt to keep a few goldfish together. Aquariums are however more expensive compared to goldfish bowls. Though, aquariums do provide more space for your fish to swim about. Goldfish require oxygenated water to survive and aquariums offer a larger surface area of water into which oxygen can diffuse. This enables your fish to breathe without the need to swim to the surface of the water repeatedly.
Aquariums provide enough space for your goldfish to swim, grow and hide. Additionally, organising and fixing the necessary equipment into the aquarium is effortless compared to putting them into a goldfish bowl. Trying to fit equipment into a goldfish bowl can be a problem due to insufficient space.
Step 2: Setting Up The Tank
What type of water should you fill your aquarium with?
Without a doubt, it is better to get a dechlorinator. A dechlorinator is a chemical additive that makes the chlorine and chloramine in your aquarium water harmless to your fish.
Using untreated tap water or drinking water, which has chemicals and minerals, could harm your goldfish.
The ideal water temperature for your goldfish is between 18 to 20oC. You can use a thermometer to constantly check the water temperature and ensure that the temperature is never above 23.5oC.
Your aquarium should be away from direct sunlight as the heat will make your fish ill.
Furthermore, to ensure that your aquarium is clean all the time, getting an algae eater fish is worth the cost. You can get ‘Loaches’, or ‘Zebra Danions’ algae eater fish that go well with your goldfish.
Step 3: Housekeeping For Your Fish
It is essential to wash your aquarium thoroughly beforehand to rinse off all the dirt and chemicals.
After a good wash, start attaching the pump and filter system of your aquarium according to the directions that came along with the equipment.
Once you have set up your aquarium with dechlorinator in the water, allow the bag your fish came in to float on top of the water for at least 10 minutes.
This technique will allow your fish to adjust itself to the temperature difference before your goldfish is released into its new home.
Step 4: Feeding Time
After you have put your goldfish into its new home, sprinkle some fish food into the aquarium. Hopefully your fish will notice these and eat them.
Now that you have set up your aquarium, you can sit back and enjoy as your goldfish swims around in its new home.
Get quality fish food so that your fish can stay healthy. It is important that you feed your fish in a small amount of tiny pinches once or twice per day.
It is always better to feed your goldfish pellet food most of the time. Occasionally, you can feed your fish with some bloodworms or brine shrimps.
Remember to only feed your fish what they can eat in a duration of one minute only. Be careful not to overfeed them because goldfish can easily overeat and die.
With these steps, you will be able to give your goldfish a long, happy and healthy life. Be mindful of the fact that your goldfish is solely dependent on you and it is your responsibility to take care of it.

domain: pet


AMT Urges Action on 2014 bipartisan manufacturing agenda.
Press Release Summary:
April 23, 2014 - Letter sent by AMT's Board of Directors to U.S. congressional leadership requests action onÂ bipartisan manufacturing agenda in 2014. Specifically, said letter urges House and Senate leaders to consider legislation where common ground exists and points to several initiatives with bipartisan support that would strengthen U.S. manufacturing if enacted into law: reauthorization of America COMPETES Act; renewal of trade promotion authority; and passage of tax, regulatory, and immigration reforms.
Original Press Release
AMT - The Association for Manufacturing Technology Urges Action on a Bipartisan Manufacturing Agenda in 2014
Press release date: April 22, 2014
The letter urges House and Senate leaders to consider legislation where there is common ground and points to several initiatives with bipartisan support that would strengthen U.S. manufacturing if enacted into law, including reauthorization of the America COMPETES Act; renewal of trade promotion authority; and passage of tax, regulatory and immigration reforms.
“There are plenty of places where Congress can agree,” said AMT President Douglas K. Woods. “The National Network for Manufacturing Innovation bill is one example. It now includes a requirement that the President establish a national manufacturing strategy. AMT has been advocating for exactly that through its Manufacturing Mandate for the past several years.”
The Revitalize American Manufacturing and Innovation Act (RAMI) recently passed the Senate Commerce, Science, and Transportation Committee. The bipartisan bill, introduced by Sens. Sherrod Brown (D-OH) and Roy Blunt (R-MO), would establish a national network of regional manufacturing institutes modeled after America Makes (NAMII), the pilot institute in Youngstown, Ohio which is focused on additive manufacturing and 3D printing.
The Administration announced three new institutes earlier this year, including the Digital Manufacturing and Design Institute (DMDI) in Chicago. AMT is a partner in both America Makes and the DMDI.
The Senate RAMI bill includes a provision added as an amendment requiring the President to submit an updated National Strategic Plan for Advanced Manufacturing to Congress every four years. AMT’s Manufacturing Mandate calls for a formal national framework to strengthen a public-private collaboration focused on boosting innovation, increasing global competitiveness and building a Smartforce for today’s American manufacturing sector.
“Jumpstarting American manufacturing is the clear path toward sustainable economic growth, improved national security, and building a 21th century workforce,” the board’s letter states. “Congress has the responsibility of ensuring that a competitive manufacturing sector is at the top of the legislative agenda.”
Woods hopes AMT members will follow the board’s lead and engage their members of Congress on issues important to the manufacturing sector. “There are no better advocates for manufacturing than the manufacturers themselves. The more they are engaged, the louder the industry’s voice will be in Washington regarding what is needed to advance and maintain American manufacturing competitiveness in the global marketplace.”
Read the AMT Board Letter
For more information on The Manufacturing Mandate visit www.AMTonline.org/mandate
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Since news that ex-Emmerdale star Kelvin Fletcher would be returning to our screens this January in a tell-all series, fans have taken an avid interest in the actor's drastic change in lifestyle.
Kelvin, who lifted Strictly's glitterball trophy in 2019, swapped his town life in Oldham for a 120-acre, 18th century farm on the edge of the Peak District, along with his wife Liz, and their two children.
Now, the family have decided to reveal all in a new reality TV series, which will showcase the highs and lows of their new lifestyle.
The childhood sweethearts often share snaps of their new life on their Instagram pages, giving fans a sneak peak into what to expect in the series, Kelvin's Big Farming Adventure which airs on January 17, on BBC One.
Liz shared a candid shot to her almost 25,000 followers two days ago, to mark the seven day countdown to the show's premiere.
Throughout lockdown, the pair have been sharing snaps of their new lifestyle, which includes looking after an array of farm animals.
Kelvin and Liz look to be enjoying the rural life so far on social media.
But it's not just the adults in charge of looking after the land, the children don't mind getting their hands dirty either.
Kelvin posted this adorable snap to his Instagram yesterday, showing his daughter helping out with the pigs.
Hundreds commented on their post expressing their excitement to watch the star's new show.
The family also recently announced there will be a new addition to the Fletcher's this year, with the pair expecting a third child in 2022.


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Resident and business directory of Middleboro’ and Lakeville, Massachusetts, for 1899. Containing a complete resident, street and business directory, town officers, schools, societies, churches, post offices, notable events in American history, etc. Compiled and published by A. E. Foss & Co., Needham, Massachusetts. The following is an example of what you will find within the …
Bentleysville was a rural community of three hundred persons in southwestern Pennsylvania in 1868. It had grown around a mill that Sheshbazzar Bentley Junior and Senior operated on the southern branch of Pigeon Creek. Its history is short because as a country village it existed less than a century. The events are substantially in chronological order, beginning with the settlers over the mountains in 1750 and ending after the Centennial in 1916.
Alexander Bisset Munro was born 25 Dec. 1793 at Inverness, Scotland to Donald and Janet (Bisset) Munro. Alexander left Scotland at the age of 14, and lived in Dimecrana in the West Indies for 18 years. He owned a plantation, raising cotton, coffee and other produce. He brought produce to Boston Massachusetts on the ship of Solomon Dockendorff. To be sure he got his money, Solomon asked his to come home with him, where he met Solomon’s sister, Jane Dockendorff. Alexander went back to the West Indies, sold out, and moved to Round Pond, Maine, and married Jane. They had 14 children: Janet, Alexander, Margaret, Nancy, Jane, Mary, Solomon, Donald, John, William, Bettie, Edmund, Joseph and Lydia.
Tracing ancestors in Lowell, Massachusetts online and for free has been greatly enhanced by the University of Massachusetts in Lowell which provided digitized version of a large quantity of the Lowell public records. Combined with the cemetery and census records available freely online, you should be able to easily trace your ancestors from the founding of Lowell in 1826 through 1940, the last year of available census records. To add color to the otherwise basic facts of your ancestors existence we provide free access to a wide range of manuscripts on the history of Lowell, it’s manufactures and residents.

domain: history


It’s always interesting returning to a place you knew very, very well. You have a picture in your head, a deep memory in glowing technicolour. The beach, sunset on the river, summer days, winter storms, road junctions, how to get to places. But it’s a moment in time, a photograph. Since you recorded those memories the world has continued to turn.
That’s how it is with me and Perth. I grew up there, lived there, worked there until I finally left in 1996 and haven’t been back since 2005. Even then, it had grown, creeping up and down the coastal plain between the Darling Ranges and the Indian Ocean. So we head out of Geraldton along the coast road, into increasingly familiar territory. Down there, the red sandstone gives way to limestone covered in bright white sand. Grass trees (black boys in my day – politically correct can be so inane) share the scrub with cycads and low, gnarled banksia trees. Spring is beginning and the yellows and purples of early flowering species brighten the drab grey-green of the tough Australian bush.
The ocean is as I remember it. Reefs and low islands line the coast, providing safe nesting sites for sea birds, rich grounds for fishermen – and a deadly snare for one Dutch ship. We drop into the small fishing village of Leeman for a comfort stop. There’s a story in that name – I’ll tell it to you later. But even here, the whisper of the approaching, encroaching city is in the air. Properties for sale for half a million? Out here? In the scrub?
We have fish and chips for lunch at Jurien Bay, sharing the last chips with the seagulls. Back home in Hervey Bay the ibises are the scavengers, but here the sea gulls hang around, awaiting their chance. A pile of chips disappears under a squawking, screeching flurry of grey and white wings. But only for a few seconds. The food gone, they disperse.
On to Lancelin and Two Rocks. Back when I was a girl, coming out here was a bone-shuddering odyssey through farm land to a deserted beach where the spear fishing was good. Not anymore. Suburbia has created a beach head. The freeway and the railway follow close behind, providing the logistical feed from the city by the Swan.
We swear a lot at the god-awful GPS in the car which seems to think we give a rats about what servos there may be near the freeway to the extent said information covers half the screen, with no findable option to turn the feature off. Because we want ROAD DIRECTIONS we resort to an old, printed map and sign-reading to avoid the city. We only just manage to avoid having a major, in-car war but sense prevails and we make the eastern suburbs without spilling blood on the car seats. I’m coming down with a cold. What bliss. Being ill on the road isn’t nice, and I have no wish to share my germs with my relatives, who are in complete agreement.
Sunday is with us. I try hard to stay in bed and rest but I’m not sleeping and the antihistamines are masking the worst of my symptoms so we head on out. If I infect anybody, they won’t know it was me. The city to surf ‘fun run’ is on, so we avoid the city and King’s Park. I have to wonder why they’re called fun runs. This one claimed two lives. Anyway – off to Fremantle, Perth’s port.
My dad worked there when I was young, a grimy, sleepy, industrial port with some lovely old buildings nobody noticed. Then Alan Bond won the America’s Cup and Freo became all the rage. The old buildings were cleaned up, the markets became a Mecca, boutique breweries, quaint shopping precincts in quirky lanes, all kinds of restaurants rose up to support the pre-existing fish and chip shops at the fishing boat harbour. I wonder how much the years have changed her.
I’m pleased to see that Freo is all of those things, only more so. The city is packed with people enjoying the day, despite (or maybe because of) the threatening clouds on the Western horizon. We buy coffee at the fishing boat harbour, which now boasts sit-down venues with fancy fish tanks. Back in the day, you bought your chips wrapped in paper and took them back over the walkway to the park to eat them on the grass under the pine trees. They cost a lot less then, too.
We go and visit the Maritime Museum (what a surprise) and see the mortal remains of the Batavia’s hull on display with its ballast cargo, a portico destined for the fort at Batavia.
And here I encounter an old friend, a skeleton I first saw when I was about ten, the victim of Jeronimus Cornelisz’s thugs. I recalled that long-ago meeting when I explained why I wrote To Die a Dry Death. I also think about my recent visit to the site of the tragedy, the Abrolhos Islands just off Geraldton. This man died far from the green fields of his home land.
We are too late to get on board the replica of the tiny yacht Duyfken but we can at least marvel at the size of the ship which had arrived on Australia’s northern shores from Amsterdam in 1606. Wow, those guys were tough.
And those threatening skies? They provide me with a perfect photo opportunity.


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text:
TMX Group to Launch Cryptocurrency Brokerage
Cryptocurrency investors rejoice! TMX Group, the operator of Canada’s leading stock exchange, has announced that its wholly-owned subsidiary, Shorcan Digital Currency Network, will partner with a specialist in decentralized financial services, Paycase Financial, to launch a cryptocurrency brokerage service. The partnering will use BMO Financial Group’s payment and settlement infrastructure and Paycase’s cryptocurrency aggregation platform to provide clients with “liquid, efficient and reliable brokerage services”. The news is perhaps another example that cryptocurrencies are here to stay.
Initial Focus will be on Bitcoin and Ether
The brokerage, named “Shorcan Digital Currency Network”, will initially focus on trading of Bitcoin and Ether, and is anticipated to launch in the second quarter of 2018. While TMX Group has not released further statements detailing how the brokerage will function, the brokerage intends to compile data on cryptocurrencies and establish public performance benchmarks based on data from the world’s leading cryptocurrency exchanges and over the counter brokered volume.
A Move that Highlights Canada’s Innovative Spirit
The partnership is a step forward in the execution of the TMX Group’s digital strategy and showcases the innovative and entrepreneurial spirit in Canada’s thriving traditional and non-traditional markets. Canada will not only be home to the first public cryptocurrency brokerage but is paving the way for the financial world of the future.
“Shorcan DCN represents a significant step forward in the execution of TMX Group’s digital strategy. As new technologies continue to reshape the global financial industry, we continue to explore new ways to evolve our business to address client needs in both traditional and non-traditional markets.” — John Lee, Managing Director, Enterprise Innovation & Product Development, TMX Group
The brokerage will certainly put Bitcoin and Ether under the microscope and may bring more legitimacy to the market in Canada. Similarly, by focussing on Bitcoin and Ether, the TMX Group has implicitly backed their stability. But will the new brokerage incite new investors to dip their toes into the e-currency markets? We will have to wait until the launch date to tell.

domain: finance


A new report has revealed a disparity between consumers’ expectations regarding improved video quality and delivery mechanisms and their willingness to pay.
The study produced by Forrester Research on behalf of Cisco, found that just 11% of consumers that were dissatisfied with their broadband speeds would be prepared to pay either for increases in broadband speeds or guaranteed increases in video quality online. 64% of consumers think that online video quality is poorer than that delivered via traditional broadcasting. Consumers hold both ISPs and content providers responsible for quality problems. 43% of those surveyed believe their ISP is responsible for ensuring good online video quality while 41% laid the blame at the door of the content provider. 72% say they experience stuttering and freezing of online video.
“With video predicted to make up more than 91% of all internet traffic by 2014, it is clear that the growth of online video represents the next significant stage in the development of the Internet,” Phil Smith, vice president and managing director, Cisco UK and Ireland. “The fact that consumers hold ISPs and content providers equally responsible for any drop in video quality is a clear sign that these industries need to work together to ensure that are able to deliver a consistently high quality service to consumers.”
When it came to television 57% of UK consumers now claim to own an HD television, a figure typically opposed to the take-up of HD subscriptions from the likes of Sky and Virgin. 43% of 16 to 24 year olds expressed an interest in 3DTV, as did 33% of those aged 25 to 34.


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Preparation and Biocompatibility of Core-Shell Microspheres for Sequential, Sustained Release of BMP-2 and VEGF
Bone defect repair remains a challenge in orthopedics. This study describes the development and potential effectiveness of vascular endothelial growth factor (VEGF)/bone morphogenetic protein-2 (BMP-2) shell-core microspheres for promoting bone regeneration. Poly(L-lactic acid)/polylactic-co-glycolic acid (PLLA/PLGA) core-shell microspheres loaded with VEGF and BMP-2 were prepared by a coaxial electrospray technique, and their surface morphology, core-shell distribution, and particle size were examined. Different groups of microspheres were prepared with different placement of the growth factors, and the encapsulation efficiency and in vitro release curves were measured. Additionally, the effects of the different groups of microspheres on the proliferation and differentiation of osteoblasts and vascular endothelial cells were investigated. The prepared microspheres had a core-shell structure with good homogeneity and dispersion, a clear boundary, and a smooth surface. On scanning electron microscopy, the mean diameter of the microspheres was similar for all six preparations (). During in vitro release, growth factor was initially released via a brief burst release from the outer shell of the microsphere followed by a slower sustained release. The release of growth factors from the inner core remained relatively slow and sustained. Sequential release of different growth factors was achieved through the inconsistent release rates from the microsphere shell and inner core. All groups of microspheres showed no cytotoxicity, good biocompatibility, and the ability to promote osteoblast proliferation. The microspheres loaded with BMP-2 also promoted osteoblast differentiation, and VEGF-loaded microspheres promoted the proliferation and differentiation of vascular endothelial cells. The BMP-2 (core)/VEGF (shell) microsphere group best promoted osteoblast differentiation. The microspheres prepared in this study exhibited slow sequential release of BMP-2 and VEGF and showed good biocompatibility along with the ability to promote osteoblast differentiation and vascular endothelial cell proliferation.
Bone defect repair continues to be a major challenge in the field of orthopedics. Growth factors can promote bone regeneration and have been used in clinical practice. However, local direct administration of growth factors results in a short half-life, easy inactivation, and rapid dilution and metabolism. Therefore, strategies for prolonging the action of growth factors in the body and maintaining appropriate drug concentrations have become a research focus. The development of drug delivery technology has produced degradable drug carriers and controllable delayed drug release systems that can prolong the action time and improve drug concentration in local lesions [1, 2]. Within the complex and highly coordinated process of natural bone development and defect repair, angiogenesis is a necessary condition for bone morphogenesis . Accordingly, biomaterials that simulate appropriately timed osteogenesis and angiogenesis are needed to promote the repair of bone defects.
Bone morphogenetic protein-2 (BMP-2) possesses favorable osteoinductive activity and plays an essential regulatory role in the process of normal osteogenic differentiation. Nevertheless, bone defect repair is a complex physiological process involving coregulation of various cytokines. Multiple studies have indicated that vascular invasion plays an important role in bone injury repair and regeneration [4, 5]. Vascular endothelial growth factor (VEGF) is the main growth factor that promotes angiogenesis in vivo. VEGF promotes the proliferation and differentiation of vascular endothelial cells (VECs) and regulates the process of angiogenesis. Thus, BMP-2 and VEGF both play critical roles in osteogenesis and have complementary biological functions that can promote bone formation. Thus, their combined use in bone tissue engineering approaches may be more beneficial than the use of either factor alone.
To date, several types of encapsulation technologies have been developed for realizing the timed release of different growth factors [6–8]. Considering their application for multipurpose drug delivery and easy integration into many scaffold matrices, core-shell microspheres are an attractive option for sequential delivery of growth factors. In regenerative medicine, particle size is an important issue in clinical applications . The inherent disadvantage of large spheres is the potential retention within scaffolds, especially for spheres with a complex porous three-dimensional structure, resulting in the loss of a uniform distribution of the encapsulated factors in the matrix or tissue. However, very small nanospheres are easily engulfed by surrounding cells, which limits their residence time in the implantation area and weakens their biological effects . Considering the above-mentioned issues, we speculated that micron-sized core-shell spheres might not only be a favorable choice for sustained and timely release of factors that promote osteogenesis and angiogenesis but also could achieve synergistic effects via simulation of a synchronous balance of angiogenesis and osteogenesis in the process of bone formation.
For clinical application, to avoid the potential shortcomings of autologous bone and allogeneic bone, bioactive bone repair materials have been actively pursued. The key strategy for designing biomaterials for bone repair is to simulate the natural bone healing process. In the present study, poly(L-lactic acid)/polylactic-co-glycolic acid (PLLA/PLGA) microspheres loaded with VEGF and BMP-2 were prepared by the coaxial electrospray method to achieve sequential, sustained growth factor release for the ultimate purpose of simulating the bone repair process and promoting the formation of new blood vessels within new bone. The prepared microspheres were characterized, and their effects on the proliferation and differentiation of osteoblasts and VECs were investigated.
2. Materials and Methods
PLGA, PLLA, BMP-2, VEGF165, sodium β-glycerophosphate, ascorbic acid, and coumarin-6 were purchased from Sigma-Aldrich (St. Louis, MO, USA). The MC3T3-E1 Subclone-14 osteogenic precursor cell line and human umbilical vein endothelial cell line EA.HY926 were obtained from Cell Resource Center, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences. Alpha Minimal Essential Medium (α-MEM), high-glucose Dulbecco’s Modified Eagle Medium, fetal bovine serum, double antibiotic solution (streptomycin and penicillin), and 0.25% trypsin were purchased from Hyclone (Logan, UT, USA). Osteopontin (OPN) antibody, β-actin antibody, runt-related transcription factor 2 (RUNX2) antibody, horseradish peroxidase- (HRP-) labeled goat anti-rabbit IgG, and HRP-labeled goat anti-mouse IgG were bought from Proteintech (Rosemont, IL, USA). Enzyme-linked immunosorbent assay (ELISA) kits for BMP-2 and VEGF were obtained from Cusabio Biotech Co., Ltd. (Wuhan, Hubei, China). A CCK-8 test kit, live/dead cell staining kit, alkaline phosphatase (ALP) detection kit, ALP staining kit, and nitric oxide (NO) detection kit were purchased from Shanghai Beyotime Biotechnology Co., Ltd. (Shanghai, China). Alizarin red dye and a kit for reverse transcription polymerase chain reaction were obtained from Beijing ComWin Biotech Co., Ltd. (Beijing, China).
The coaxial electrospray device consisted mainly of an electrostatic spinning machine and a coaxial needle, as shown in Figure 1. The internal and external diameters of the outer tube of the coaxial needle were 0.50 mm and 0.72 mm, respectively, and those of the inner tube were 0.20 mm and 0.40 mm, respectively.
2.2. Preparation of Microspheres
Six microsphere formulations were prepared: (1) BMP-2 in the core and VEGF in the shell (BMP-2/VEGF group); (2) BMP-2 in the core and no factor in the shell (BMP-2/blank group); (3) no factor in the core and VEGF in the shell (blank/VEGF group); (4) two factors, BMP-2 and VEGF, in both the nucleus and shell (double/double group); (5) VEGF in the core and BMP-2 in the shell (VEGF/BMP-2 group); (6) no factor in either the core or shell (blank/blank group).
The preparation solutions for blank microspheres consisted of 500 mg PLGA (molecular weight 40,000 Da) in 10 ml dichloromethane (DCM) and 500 mg PLLA (molecular weight 90,000 Da) in 10 ml ethyl acetate (EA). The preparation solutions for factor-loaded microspheres consisted of VEGF in deionized water (10 μg/ml), BMP-2 in deionized water (100 μg/ml), PLGA in EA (5%, w/v), and PLLA in DCM (5%, w/v). The growth factor solution served as the aqueous phase and the polymer solution as the organic phase. The aqueous and organic solutions were mixed at a volume ratio of 1 : 10 and placed in an ultrasonic shaker until a homogeneous emulsion was formed. The details for each microsphere preparation are shown in Table 1.
The polymer concentration was set at 5%; the flow rates of the solutions in the inner and outer tubes of the coaxial needle were set at 1.5 ml/h, and the voltage was set at 10.0 kV. The injection pumps for the PLGA and PLLA solutions were connected to the outer needle tube and the inner needle tube of the coaxial needle, respectively. The electrospinning machine was initiated, and the voltage was adjusted progressively to 10.0 kV. As the voltage was increased, the solution leaving the tip of the coaxial needle changed from a droplet shape to a linear shape, then finally to mist-like droplets, and ultimately a stable Taylor cone. The microspheres were collected about 15 cm below the coaxial needle tip in a glass vessel filled with an appropriate amount of absolute ethanol. The collected anhydrous alcohol microsphere suspension was transferred to a 50 ml centrifugal tube, centrifuged for 3 min at , and then washed with double-steamed water three times after removal of the ethanol from the upper layer. Next, the solution was incubated at -80°C for 30 min, freeze-dried for 72 h, and stored in the refrigerator at 4°C away from light for use.
2.3. Observation of Core-Shell Microsphere Structure
For observation of core-shell microsphere structure under confocal laser scanning microscopy (CLSM), microspheres were prepared with a trace of coumarin-6 added in the PLLA/DCM solution to dye this layer light green. For observation of the surface morphology and particle size of the core-shell microspheres by scanning electron microscopy (SEM), freeze-dried microspheres were sprayed with gold for 60 sec and then observed. For the measurement of microsphere diameter, two fields of view were randomly selected for each group of microspheres, and 10 microspheres were randomly selected in each field for diameter measurement.
2.4. Determination of Growth Factor Encapsulation Efficiency in Core-Shell Microspheres
Three samples of each microsphere formulation were weighed, and 20 mg of each sample was dissolved in 1 ml DCM by ultrasonic vibration at low temperature. After the core-shell structural polymers PLGA and PLLA were completely dissolved, 1 ml phosphate-buffered saline (PBS) was added. This solution was vortexed for 10 min and then placed in a low-temperature high-speed centrifuge at for 3 min. After centrifugation, the aqueous layer was carefully absorbed. This procedure was repeated twice, and then the VEGF and BMP-2 concentrations in the recovered solutions were determined by ELISA. The encapsulation efficiency was calculated as follows: .
2.5. Measurement of In Vitro Growth Factor Release from Core-Shell Microspheres
Samples consisting of 20 mg microspheres were placed in a dialysis bag and then in a centrifuge tube containing 10.0 ml PBS. The centrifuge tube was then placed on a constant temperature (37°C) orbital shaker at 120 rpm. At the indicated time points (1, 2, 4, 6, 8, 11, 14, 18, 22, or 27 days), the PBS from the centrifuge tube was aspirated and immediately replaced. The recovered PBS was stored at –20°C until analysis. The concentrations of BMP-2 and VEGF in the solutions collected at each time point were measured by ELISA, and the released amounts were calculated for preparation of release curves.
2.6. In Vitro Evaluation of Core-Shell Microsphere Biocompatibility
2.6.1. Cell Culture
MC3T3-E1 cells were cultured in α-MEM containing 10% fetal bovine serum and 1% double antibiotic solution (100 U/ml of both streptomycin and penicillin) in a cell incubator at 37°C with 5% CO2, and the medium was changed every 2 days. The cells were passaged at 80%–90% confluency and subcultured to the P3 generation for use in experiments.
2.6.2. Exposure of Cells to Microspheres
P3 generation MC3T3-E1 cells at a concentration of cells/ml in 1 ml medium were added to the lower chamber of a 24-well Transwell plate, and 20 mg of the specified core-shell microsphere formulation was placed in the upper chamber. For the control group, the wells were seeded with the same number of cells, but no microspheres were added to these wells. Three wells were prepared for each group. The solution was changed every 2 days.
2.6.3. Measurement of Osteoblast Proliferation upon Exposure to Factor-Loaded Core-Shell Microspheres
After 1, 3, 5, and 7 days in culture with the microspheres, 50 μl CCK-8 solution was added to each well for further incubation for 4 h. The supernatant from each well was then carefully collected and transferred to the wells of a 96-well plate. The amount of solution was adjusted to 100 μl/well, and the optical density (OD) value was detected at 450 nm wavelength by a microplate reader.
2.6.4. Measurement of Osteoblast Activity upon Exposure to Factor-Loaded Core-Shell Microspheres
After 3 days in culture with the microspheres, the Transwell plate chambers were discarded, the medium was aspirated, and the cells were washed three times with PBS. The prepared live/dead cell staining working solution (10 ml with 8 μM propidium iodide and 2 μM calcein AM) was added for incubation at room temperature for 45 min. After removal of the staining solution, a trace of PBS was added, and the labeled cells were observed under a fluorescence microscope.
2.7. Evaluation of the Effects of Factor-Loaded Core-Shell Microspheres on Osteoblast Differentiation
2.7.1. Detection of ALP Activity
Osteogenic induction medium (100 ml α-MEM +316 mg sodium β-glycerophosphate +5 mg ascorbic acid +5 μL dexamethasone) was used to induce differentiation of MC3T3-E1 cells cultured with the different core-shell microsphere formulations. The medium was changed every 3 days. After the 12th day of osteogenesis induction, ALP activity was measured using two methods. Some cell samples were washed with PBS three times and fixed with 4% paraformaldehyde for 2 min. Then, the cell fixation solution was removed, and an appropriate amount of ALP staining working solution was added. The cells were incubated in darkness at room temperature for 20 min and observed under an inverted microscope. Other cell samples collected on the 12th day of osteogenic induction were used for detection of ALP activity by an enzyme labeling method. The collected cells were fully lysed with cell lysis buffer, washed three times with PBS, and centrifuged at for 10 min. ALP activity was quantified using an ALP assay kit.
2.7.2. Alizarin Red Staining
On the 14th day of osteogenic induction, cells in each group were collected, washed twice with PBS, and fixed with 4% paraformaldehyde for 30 min at room temperature. After removal of the cell fixation solution, the cells were washed with PBS for three times. Then, the cells were stained with Alizarin red for 5 min and washed with PBS for three times. The stained cells were observed under an inverted microscope.
2.7.3. Detection of Osteogenesis-Related Gene Expression by Real-Time PCR
Cells were collected after 14 days of osteogenic induction. The total RNA of each group was extracted and reverse transcribed into cDNA. The mRNA expression levels of RUNX2, osteocalcin (OCN), and OPN were detected by real-time quantitative PCR using the primer sequences listed in Table 2.
The PCR cycling parameters were set as follows: predenaturation at 95°C for 10 min, denaturation at 95°C for 15 s, and annealing at 60°C for 30 s for 40 cycles. The final extension step was conducted at 72°C for 10 min. The end products were subjected to 1.5% agarose gel electrophoresis, and actin was used as the internal reference gene.
2.7.4. Detection of Osteogenesis-Related Protein Expression by Western Blotting
Cells were collected after 21 days of osteogenic induction. The protein concentration was determined by the BCA standard curve method. For western blot analysis of protein expression, the proteins were subjected to gel electrophoresis followed by transfer to nitrocellulose membranes. The membranes were then incubated overnight at 4°C with RUNX2, OPN, and β-actin primary antibodies at a dilution ratio of 1 : 1000. The next day, the membranes were incubated with secondary antibodies at a dilution ratio of 1 : 10000 at room temperature for 2 h, before being three 10 min washes with Tris-buffered saline containing Tween 20 (TBST) solution. Enhanced chemiluminescence solution was added to the washed samples, incubated for 1 min, and developed for detection of the absorbance and molecular weight of labeled proteins.
2.8. Evaluation of the Effects of Factor-Loaded Core-Shell Microspheres on VECs
2.8.1. Measurement of VEC Proliferation, Activity, and NO Secretion
EA.hy926 cells of the P3 generation were exposed to different formulations of microspheres following the same Transwell culture method used for osteoblasts. The proliferation and activity of VECs were evaluated using the same CCK-8 detection and live/dead staining methods used for osteoblasts. The amount of NO secretion was detected using a NO detection kit according to the manufacturer’s instructions.
2.8.2. Detection of Angiogenesis-Related Gene Expression by Real-Time PCR
Expressions of the angiogenesis-related genes VEGF and hypoxia-inducible factor 1 alpha (HIF-1α) were detected by real-time quantitative PCR using the primer sequences listed in Table 3.
2.9. Statistical Analysis
SPSS 24.0 software was used for all statistical analyses, and the data are expressed as deviation. One-way analysis of variance was performed to identify differences among the groups. Differences were considered significant if values were less than 0.05.
3.1. Structure and Size of the PLLA/PGLA Core-Shell Microspheres
Under optical microscopy, the microspheres exhibited an obvious core-shell structure, round shape, and good uniformity. Under CLSM, the morphology of the microspheres was found to be a clear and obvious core-shell structure. Under SEM, the microspheres had a regular morphology, strong stereoscopic impressions, round and smooth surface, and no obvious particle–particle adhesion (Figure 2).
As measured in SEM images, the mean diameter of the microspheres was similar for all six preparations (). The mean microsphere diameters were μm for the BMP-2 (core)/VEGF (shell) group, μm for the BMP-2/blank group, μm for the blank/VEGF group, μm for the double/double group, μm for the VEGF/BMP-2 group, and μm for the blank/blank group.
3.2. Growth Factor Encapsulation in Core-Shell Microspheres
The encapsulation efficiency of the microsphere preparation process was evaluated using ELISA kits to measure the concentrations of growth factors contained within the dissolved microspheres. The encapsulation efficiency was calculated by dividing the amount of recovered growth factor by the amount used in the microsphere preparation. Some variation was observed in the encapsulation efficiency among the different formulations, and this can be attributed to the different locations of the growth factors in different groups of microspheres (Table 4).
3.3. Sustained Growth Factor Release from Core-Shell Microspheres In Vitro
Figure 3 shows the growth factor release curves for the five groups of growth factor-loaded microspheres. The corresponding cumulative release kinetics showed that sequential release of two growth factors was achieved in the BMP-2/VEGF and VEGF/BMP-2 groups. The growth factor in the shell was released initially in a short burst and then gradually at a sustained level, while the release of growth factor from the core was always relatively steady. Overall, sequential release of different growth factors was achieved through the inconsistent release rates of the shell and core materials.
3.4. Effects of Growth Factor-Loaded Core-Shell Microspheres on Osteoblast Viability
Live/dead staining showed no obvious dead cells in any group after exposure to microspheres for 3 days. Thus, none of the microsphere formulations was toxic to the cells, indicating their good biocompatibility. In agreement with the proliferation assay results, the double/double and control groups had lower cell numbers at this time point, and no connections were observed between these cells. The BMP-2/blank, blank/VEGF, and blank/blank groups had more cells, with some connections observed between cells. The BMP-2/VEGF and VEGF/BMP-2 groups had the highest numbers of cells, with abundant connections and spreading observed in these groups (Figure 4(a)).
As shown in Figure 4(b), after 1 day of exposure of the different formulations of microspheres, no difference in the number of cells was observed among the groups (). After 3 days of exposure to the microspheres, the number of cells in each group had increased significantly. The BMP-2/VEGF, BMP-2/blank, blank/VEGF, VEGF/BMP-2, and blank/blank groups showed higher cell numbers than the control group not exposed to microspheres (), and the mean numbers of cells in the double/double and control groups showed no significant difference. After 5 days in culture, the BMP-2/blank, double/double, VEGF/BMP-2, and blank/blank groups showed higher cell numbers than the control group (), and no significant difference was observed among the BMP-2/VEGF, blank/VEGF, and control groups (). After 7 days in culture, the BMP-2/VEGF, VEGF/BMP-2, and blank/blank groups had higher cell numbers than the control group (), while no significant difference was observed among the BMP-2/blank, blank/VEGF, double/double, and control groups ().
3.5. Effects of Growth Factor-Loaded Core-Shell Microspheres on Osteoblast Differentiation
Compared with the blank/blank and no microsphere control groups, ALP staining was visibly increased in cells exposed to microspheres loaded with BMP-2, including the BMP-2/VEGF, BMP-2/blank, double/double, and VEGF/BMP-2 groups, and the staining intensity was darker for the BMP-2/VEGF group than for the other groups (Figure 5(a)). The results for ALP quantification are depicted in Figure 5(c). Osteoblasts exposed to the BMP-2/VEGF, BMP-2/blank, double/double, and VEGF/BMP-2 microspheres produced significantly more ALP than those exposed to the blank control microspheres (), and ALP production did not differ significantly among the blank/VEGF, blank/blank, and control groups ().
Alizarin red staining was more apparent in the BMP-2/VEGF, BMP-2/blank, double/double, and VEGF/BMP-2 groups than in the no microsphere control group. Alizarin red staining showed that the content of calcium nodules in these groups was higher than that in the control group, but no significant difference was observed among the blank/VEGF, blank/blank, and control groups (Figure 5(b)). Quantitative analysis of alizarin red staining showed that the content of calcium nodules in the BMP-2/VEGF group was significantly higher than that in the no microsphere control group (), and the content of calcium nodules was also higher in the BMP-2/blank, double/double, and VEGF/BMP-2 groups than that in the control group (; Figure 5(d)). The content of calcium nodules did not differ significantly among the blank/VEGF, blank/blank, and control groups ().
Osteoblasts exposed to each of the microsphere formulations loaded with BMP-2 (BMP-2/VEGF, BMP-2/blank, double/double, and VEGF/BMP-2 microspheres) expressed higher levels of osteogenic RUNX2, OCN, and OPN genes compared with cells in the control group not exposed to microspheres (), while the expression levels of these genes did not differ significantly among the blank/VEGF, blank/blank, and control groups (). Expression of the RUNX2 gene was not significantly different in the BMP-2/VEGF group compared with the BMP-2/blank, double/double, and VEGF/BMP-2 groups (). However, expression of the OCN gene was higher in the BMP-2/VEGF group than in the double/double and VEGF/BMP-2 groups () but did not differ significantly between the BMP-2/VEGF group and the BMP-2/blank group (). Expression of the OPN gene was higher in the BMP-2/VEGF group than in the BMP-2/blank and double/double groups () and higher than that of VEGF/BMP-2 group (; Figure 6(a)).
Consistent with the results for osteogenic gene expression, the relative expression of RUNX2 protein in cells exposed to the BMP-2–loaded microspheres was greater than that in the no microsphere control group ( for the BMP-2/VEGF, BMP-2/blank, and VEGF/BMP-2 groups and for the double/double group). No significant difference in RUNX2 protein expression was observed among cells exposed to microspheres not loaded with BMP-2 ( for the comparison of the blank/VEGF and blank/blank groups with the control group). The relative expression of OPN protein also was greater in cells exposed to the BMP-2–loaded microspheres than in cells exposed to the BMP-2/VEGF and VEGF/BMP-2 ( for the BMP-2/VEGF and VEGF/BMP-2 groups and for the BMP-2/blank and double/double groups), while again, no significant difference was observed between the blank/VEGF and blank/blank groups compared with the control group (5). Furthermore, the protein expression levels of both RUNX2 and OPN were significantly higher in the BMP-2/VEGF group than in the BMP-2/blank, double/double, and VEGF/BMP-2 groups (; Figure 6(b)).
3.6. Effects of Growth Factor-Loaded Core-Shell Microspheres on VEC Viability
Live/dead staining of VECs after exposure to microspheres in culture for 3 days showed no obvious cell death in any group, further confirming the biocompatibility of the growth factor-loaded core-shell microspheres (Figure 7(a)).
On days 1 and 3 in culture with the different microsphere formulations, the numbers of VECs showed no differences among the groups (). However, on the 5th day in culture, VEC numbers were higher in the BMP-2/VEGF and blank/VEGF groups than in the no microsphere control group (), while no significant difference in cell number continued to be observed for comparison of the BMP-2/blank, double/double, VEGF/BMP-2, and blank/blank groups with the no microsphere control group () (Figure 7(b)).
The results for NO secretion by VECs exposed to different microspheres are shown in Figure 7(c). Significantly greater NO secretion was detected in all cell groups exposed to VEGF-loaded microspheres compared with the no microsphere control group ( for the BMP-2/VEGF group and for the blank/VEGF, double/double, and VEGF/BMP-2 groups).
3.7. Effects of Growth Factor-Loaded Core-Shell Microspheres on the Angiogenic Activity of VECs
The expression levels of the angiogenesis-related VEGF and HIF-1α genes were significantly higher in all groups of cells exposed to VEGF-loaded microspheres ( for the BMP-2/VEGF, blank/VEGF, double/double, and VEGF/BMP-2 groups compared with the control group), while no differences in the expression levels of these genes were detected in the BMP-2/blank and blank/blank groups compared with the no microsphere control group (; Figure 7(d)).
Despite the widespread topical use of growth factors in clinical practice, challenges remain with their delivery, due to their short half-life, easy inactivation, and easy dilution metabolism. In recent years, much research has been carried out on materials designed for the slow sustained release of growth factors, and remarkable progress has been achieved. New slow-release composite systems can slow the release rate of growth factors, thereby increasing their bioavailability.
Sustained-release composite systems have been tested for a variety of important growth factors and shown to offer synergistic release kinetics and provide a promising method for enhancing bone regeneration by simulating the cascade of spatiotemporal signals involved in natural bone development and spontaneous healing [11–13]. Core-shell microspheres specifically have demonstrated great potential for achieving sustained release of growth factors . In the present study, we successfully manufactured different formulations of core-shell microspheres by a coaxial electrospray technique, in which the PLGA and PLLA portions were loaded with VEGF or BMP-2. Our results revealed that growth factor activity was well maintained during the microsphere preparation process, and sequential release of growth factors was achieved.
At present, many methods have been reported to prepare putamen microspheres, including an emulsion solvent evaporation method, electrostatic spray method, electrostatic dripping method, and self-assembly method. Coaxial electrospray has been proven to offer the advantages of maintaining the structural integrity of microspheres, reducing the particle size distribution, and maintaining the biological activity of loaded proteins [14, 15]. In the present study, two types of drugs with different physicochemical properties (water soluble or fat soluble) were successfully embedded in the outer shell and inner core of the putamen polymer microspheres by coaxial electrospray, which allows for release of the two drugs simultaneously or sequentially. By changing the relative size of the nuclei in the putamen structure, the release profiles for the two drugs can be precisely controlled. Chang et al.  successfully manufactured a hollow microsphere with only a shell component using coaxial electrospray, with polymethylsilsesquioxane as the model shell material encapsulating a volatile liquid perfluorohexane as the core, which was then evaporated. Another study, focusing on the control of initial release, prepared core-shell microspheres using PLGA and alginate and confirmed that high molecular weight PLGA better inhibited the initial burst release of protein compared to low molecular weight PLGA .
Therefore, the ability to generate particles with a core-shell structure that can continuously release two drugs via a simple fabrication method is of great significance. Toward this goal, the present study investigated the release characteristics of core-shell microspheres prepared simply by high-voltage coaxial electrospray. During the fabrication process, the major factors responsible for maintaining the stability of the microsphere core-shell structure were balanced among electrostatic repulsion, surface tension, viscoelastic force, and flow rate. In our preliminary experiments, the experimental conditions for high-voltage coaxial electrospray were explored thoroughly. The electrostatic repulsion was adjusted by changing the voltage, and a voltage of 10 kV was found to achieve core-shell microspheres with the best structure and shape. In addition, the liquid flow rates in the inner and outer tubes were set at 1.5 ml/h assuming the inner and outer tube diameters of the coaxial needle were fixed. In the present study, PLGA was dissolved in EA, and PLLA was dissolved in DCM, due to the extremely low solubility of PLLA in EA, which effectively reduced the dispersion of the solutions in the inside and outside tubes of the coaxial needle tip during high-voltage electrostatic spray . Meanwhile, the concentrations of 5% PLLA solution and 5% PLGA solution had the optimal effect on core-shell microsphere preparation.
Our results indicate that the core-shell microspheres prepared by high-voltage coaxial electrospray could not only maintain the activity of growth factors but also realize the independent release of the two growth factors governed by the placement of each factor in the two-component particles. VEGF in the shell was released in the form of an initial burst release, with nearly 70% of the loaded VEGF released in the first 10 days in solution. As reported previously, VEGF secretion occurs in the early healing stage after a bone fracture, and the peak VEGF concentration appears over 5–10 days after fracture [10, 19]. Therefore, the release pattern of VEGF achieved in this study aligns with the physiological pattern. BMP-2, which plays a key role in bone regeneration, also is produced in the process of fracture healing. BMP-2 release from the microsphere core was relatively steady, rather than a burst release, which is consistent with the physiological time course of BMP-2 production during bone defect healing . Long-term continuous administration can not only overcome the rapid degradation of BMP-2 in the complex local enzymatic environment but also avoid heterotopic ossification and postoperative hematoma and swelling caused by excessive local doses of BMP-2 . Kempen et al.  reported that sustained release of BMP-2 could enhance the curative effect of ectopic osteogenesis and improve the repair of long bone defects in situ. The above evidence further supports our conclusion that the core-shell microspheres prepared in this study can be used as an effective carrier for controlled release of two growth factors at different kinetic rates. Both VEGF and BMP-2 are hydrophilic proteins and thus rapidly dissolve in PBS. During release, VEGF in the shell is in direct contact with PBS, and thus, a burst release is possible. The chemical composition of the PLGA shell provides a barrier to slow BMP-2 diffusion from the core to the surrounding medium, thereby realizing the continuous release of both VEGF and BMP-2. The aforementioned continuous growth factor release profiles, which mimic their secretion processes in natural bone repair, represent a promising strategy for accelerating the growth factor-driven bone regeneration process [9, 13].
Maintaining the activity of growth factors is another major challenge in the use of microspheres for their delivery. Our results showed that VEGF and BMP-2 released from the PLGA/PLLA core-shell microspheres were able to promote the proliferation of VECs and the osteogenic differentiation of osteoblasts, respectively. VECs specifically targeted by VEGF are usually considered as the intimal layer of new blood vessels and play a key role in angiogenesis. Cells of the MC3T3-E1 line are precursor cells to osteoblasts, and BMP-2 can promote their osteogenesis and differentiation . Therefore, the delivery of VEGF and BMP-2 via core-shell microspheres may promote angiogenesis and osteogenesis in vivo and improve bone formation [22, 23]. In the present study, the maintenance of the biological activity of the growth factors may be attributed to the compatibility of the electrostatic spray method, which involves a step-by-step process without the use of potentially hazardous organic solvents or crosslinking agents.
The biocompatibility of the different formulations of microspheres prepared in this study was investigated in vitro. The results for cell proliferation and viability for both osteoblasts and VECs indicated that all groups of microspheres had no obvious cytotoxicity and possessed good biocompatibility. In addition, the microspheres loaded with BMP-2 in either the core or shell promoted the osteogenic differentiation of the osteoblast precursor cells, while microspheres loaded with only VEGF or no growth factor had no obvious effect on promoting the osteogenic differentiation of these cells. These findings imply that the BMP-2 released from the microspheres played an essential role in promoting bone differentiation, whereas VEGF released from the microspheres only promoted the proliferation of osteoblasts in vitro. Among the microspheres loaded with BMP-2, the BMP-2/VEGF group showed the greatest ability to promote bone differentiation. Considering these microspheres had BMP-2 in the core and VEGF in the shell, our results indicate that the sequential release of VEGF and BMP-2 had a synergistic effect on bone differentiation. This finding is consistent with the research results of Wang et al. .
With respect to the effects of growth factor-loaded core-shell microspheres on VECs, all microsphere formulations containing VEGF could promote the proliferation of VECs to some extent, as well as the expression of the angiogenesis-related VEGF and HIF-1α genes. The action of VEGF may enhance the effect of BMP-2 in promoting bone differentiation via two mechanisms. Firstly, VEGF can promote the construction of a vascular network, which then indirectly accelerates the formation of new bone . Secondly, VEGF may participate in the BMP signaling pathway and enhance the activity of BMP-2. Previous research has shown that the interaction between VEGF and BMP-2 may promote the nuclear translocation of osterix protein by activating the p38 MAPK pathway, thereby promoting osteogenic differentiation .
The coaxial electrospray technique can be applied to successfully prepare dual growth factor-loaded core-shell microspheres that can achieve the slow sequential release of VEGF and BMP-2. While all prepared core-shell microspheres showed good biocompatibility, the VEGF/BMP-2 core-shell microspheres exhibited the strongest ability to promote bone differentiation along with the proliferation of VECs.
The data that support the findings of this study are available from the corresponding authors upon reasonable request.
Conflicts of Interest
The authors declare that they have no conflicts of interests.
Zhenchao Xu and Xiyang Wang contributed equally to this work.
This work was supported by the National Natural Science Foundation of China (81672191), the Graduate Research Innovation Project of Central South University (2021zzts0356), and the Provincial Natural Science Foundation of Hunan, China (2022JJ40200).
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domain: biology


text:
President Jair Bolsonaro again cast doubt on the 2022 elections, when addressing supporters through video calls in different acts in favor of the printed vote, this Sunday (1st), in São Paulo, Rio, Brasília, Belo Horizonte and other cities.
In São Paulo, supporters gathered on Avenida Paulista. The demonstration was attended by congresswoman Carla Zambelli (PSL-SP), former Environment Minister Ricardo Salles and congressman Eduardo Bolsonaro (PSL-SP), who spoke without a mask.
Unmasked supporters carried posters calling for a paper ballot and public counting of votes.
In Brasilia, supporters gathered in front of Congress. In Rio, economist Eduardo Debaco, 49, was attacked by Bolsonaro supporters. He suffered an open fracture.
Translated by Kiratiana Freelon

domain: sociology


text:
3D Lighted Glass Balls, Set of 3 - Green
Our trio of 3D Lighted Glass Balls create a stunning holiday display with an eye-catching “starburst” effect. A special multi-layer process creates a compelling, lighted scene highlighted from within by LEDs. The result is a three-dimensional effect that is absolutely mesmerizing!
These gorgeous lighted glass globes are begging to be used as a tabletop display or placed on the mantel. Definitely a spot where guests and visitors can peer into their magical design! Feature an auto-timer for 6 hours on, 18 hours off. Each ball takes 3 AA batteries, not included.
- Glass globes with 3D effect
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- Auto-timer; 6 hours on, 18 off
- Indoor use only
- Each ball takes 3 AA batteries, not included
5" dia., 6" dia. and 8" dia.
Small 5" dia.
Medium 6" dia.
Large 8" dia.

domain: artistic


text:
- Ford SYNC users will have tens of thousands of Web-based audio stations at their fingertips
This is what you need to know before the opening bell
U.S. stock futures rise modestly Thursday after Donald Trump's tax plan fails to deliver any surprises but instead raises many more questions.
European stocks fell for the first session in nearly a week Thursday as investors reacted to a mixed set of regional corporate earnings.
European stocks are set to fall for the first day in four as investors pullback from a global equity rally after the publication of President Donald Trump's tax reform plans.


text:
Topic of the day-
No matter how much we claim that we don't care about people's opinions, there's always this little part at the back of our heads wondering how people will respond to certain behaviors, incidents in our life, a haircut or even an outfit we're wearing. We wonder if we will fit in with our looks and words, if we will belong...if we will be liked and loved. And I'm not referring to the boy-girl love people think the term is bound to. Love that exists between friends and family has been obviously forgotten but it's still there you know. So, let me speak for all forms and shapes of love. And please allow me to say that, if you do not love yourself, nobody will ever love you.
Think about if someone talks to you endlessly about a pair of horrible shoes, for instance; when you finally see the shoes, you're going to find it very difficult to see good in them even if they are classy pencil heels that will make you look taller and adjust your posture to a confident and feminine one rather than the slouched casual everyday look you're so sick of. You will see the shoes through the other person's eyes so no matter how good they are, they will always be just a little bit damaged in your sight now.
People see you through your own eyes. Your insecurities can shape your facial features. Your lack of confidence shows in your eyes that move around looking for what you think you do not have. Your poor self-esteem is bouncing around midst the circle of friends talking oh-so-confidently while you stand gaping, unsure of whether you should include yourself in the conversation or if people won't think you're smart or funny enough.
People see that. People see you not liking yourself enough and eventually, they think the same of you as you think of yourself. And why wouldn't they? Why would someone like who you are if you, yourself, do not like who you are..?!
Learn to love yourself. Seriously, no one is more worthy of being loved than YOU. No one will ever look out for you more than yourself. People come and go, even family. People move away, lose touch or (God Forbid) pass away. Only you remain with yourself until the very end of your journey in life. From beginning to end.
So, love yourself! Learn to have fun ON YOUR OWN rather than making your happiness dependent on someone who may or may not be there. Learn to enjoy your own company because if you don't, why on earth would anyone enjoy yours?!

domain: psychology


text:
Deluxa Group is a professional Connecticut-based web design firm located Meriden. We provide fully customized solutions to help your brand succeed with eye-catching design and online marketing services.
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domain: design


text:
Hangovers appear to be the body’s method of advising us about the risks of overindulgence. From a physical standpoint, it’s a group effort: Looseness of the bowels, exhaustion, headache, nausea, and shaking are the classic signs. In some cases, systolic (the top number) high blood pressure rises, the heart defeats faster than regular, and gland overproduce– proof that the “battle or trip” action is revved up. Some individuals become sensitive to light or audio. Others endure a spinning feeling (vertigo).
The reasons are as varied as the signs. Alcohol is metabolized right into acetaldehyde, a compound that’s poisonous at high levels. However, concentrations hardly ever get that high, to ensure that’s not the complete explanation.
Consuming alcohol hinders brain task throughout sleep, so a hangover may be a kind of rest deprivation. Alcohol scrambles the hormones that regulate our biological clocks, which may be why a hangover can feel like jet lag, and vice versa. Alcohol can additionally activate migraines, so some individuals may believe they’re hung over when it’s actually an alcohol-induced migraine headache they’re suffering.
Hangovers start after blood alcohol degrees start to fall. Actually, according to some experts, the worst signs happen when levels get to zero.
The vital ingredient seems to be “drinking to drunkenness”; how much you drank to get there is lesser. In fact, a number of studies recommend that light and also modest drinkers are more susceptible to getting a hangover than heavy drinkers. Yet there’s likewise apparently inconsistent research revealing that people with a family history of alcoholism have worse hangovers. Researchers claim some people might wind up with drinking problems because they drink in an effort to relieve hangover symptoms.
What helps with a hangover
Dr. Robert Swift, a scientist at the Providence Veterans Affairs Medical Center in Rhode Island, coauthored one of minority testimonial papers on hangovers in 1998. It’s still among one of the most often pointed out resources on the topic. The review on hangover treatments that adheres to is based on that evaluation, a meeting with Dr. Swift, and also numerous other resources.
1. Hair of the dog. Drinking to alleviate the signs of a hangover is often called taking the hair of the dog, or hair of the dog that little bit you. The notion is that hangovers are a form of alcohol withdrawal, so a drink or 2 will certainly reduce the withdrawal.
There may be something to it, says Dr. Swift. Both alcohol as well as particular sedatives, such as benzodiazepines like diazepam (Valium), connect with GABA receptors on brain cells, he describes. As well as it’s well recorded that some people have withdrawal signs and symptoms from short-acting sedatives as they diminish. Perhaps the mind reacts likewise as blood alcohol degrees begin to go down.
However, Dr. Swift discourages using alcohol as a hangover remedy.
“The hair of the dog just continues a cycle,” he says. “It doesn’t enable you to recoup.”
2. Consume fluids. Alcohol advertises urination because it inhibits the release of vasopressin, a hormonal agent that decreases the volume of urine made by the kidneys. If your hangover includes looseness of the bowels, sweating, or throwing up, you might be much more dried. Although nausea or vomiting can make it challenging to get anything down, even simply a couple of sips of water may aid your hangover.
3. Obtain some carbs right into your system. Alcohol consumption might reduce blood sugar level degrees, so in theory several of the exhaustion and frustrations of a hangover might be from a mind functioning without sufficient of its major fuel. In addition, lots of people neglect to consume when they drink, more reducing their blood sugar level. Toast as well as juice is a way to carefully nudge degrees back to regular.
4. Prevent darker-colored liquors. Experiments have revealed that clear alcohols, such as vodka and also gin, often tend to trigger hangovers much less often than dark ones, such as whiskey, merlot, and also tequila. The major kind of alcohol in liquors is ethanol, however the darker alcohols consist of chemically associated compounds (congeners), including methanol. According to Dr. Swift’s testimonial paper, the very same enzymes process ethanol and methanol, yet methanol metabolites are specifically hazardous, so they may cause a worse hangover.
5. Take a painkiller, yet not Tylenol. Aspirin, ibuprofen (Motrin, various other brand names), and various other nonsteroidal anti-inflammatory medications (NSAIDs) may aid with the headache as well as the general achy feelings. NSAIDs, though, may irritate a stomach already aggravated by alcohol. Do not take acetaminophen (Tylenol). If alcohol is lingering in your system, it might highlight acetaminophen’s toxic impacts on the liver.
6. Consume coffee or tea. High levels of caffeine might not have any special anti-hangover powers, however as an energizer, it can aid with the grogginess.
7. B vitamins as well as zinc. A study just recently released in The Journal of Scientific Medication evaluated the diet regimens for 24 hours prior to and after extreme drinking took place. It was a tiny research and outcomes were based on the participants saying what they ate. Nevertheless, they did find that individuals whose food and also drink usage consisted of higher quantities of zinc and B vitamins had less severe hangovers.

domain: medical