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The English countryside is one of the most enticing and enchanting locations one can visit for a vacation away from the crowd. The county of Wiltshire is no different. This makes it a perfect getaway spot for you and your loved one to spend some lonely days, together. Away from all the hustle and bustles of urban England, Wiltshire lies quaint with its historical artefacts and monuments waiting for you to explore. Book your loved one and yourself a cottage holiday in Wiltshire ; and enjoy a peaceful and timeless romantic getaway, exploring and enjoying the various historic sites nearby.
The best way to get to Wiltshire is by renting a car. Road condition to Wiltshire is normally really good, and it takes about one and a half hours to reach Wiltshire from London. Go on a romantic long drive with your partner, while enjoying the gorgeous landscapes along your way. Pass-through numerous picturesque villages along your journey. Time stands still in these beautiful countryside villages of England. Get lost in these timeless roads along with your loved one, and find the Wiltshire which belongs to one but you two.
Best time to visit
Unlike some of the other counties of England, Wiltshire remains beautiful throughout the whole year. It is not another summer location, and there will be plenty of things to do for you and your partner if you visit during the colder months.
The setting and the scenery
Wiltshire County has no shoreline, and it has only one city. However, this place is about much more than that. The landscapes of this place can only be described as ancient. From the houses to the roads to the various sites, everything about this historic county will excite your curiosity.
The focus of Southern Wiltshire, Salisbury can easily be in the race of one of the most attractive cities in England. With its famous 14th century cathedral, chalk hills and beautiful roads, a journey through this historic city will surely catch your fancy.
How can another place be more romantic when there’s actually a village named Lover in Wiltshire? The beautiful architecture of the village houses, the cobbled roads and the peaceful nature makes Wiltshire one of the best places to spend some time with your lover.
What to do in Wiltshire
There are a lot of activities to do and places to visit while you spend some time here with your loved one. The most famous of them is, of course, visiting the Stonehenge. Go for an inner circle tour with your partner and watch an incredible view of sunset or sunrise with the silhouettes of the stones in front. This will be one of the most memorable moments of all your time together.
You can also go for a picnic with your loved one to Stonehenge’s little-known sister, the Avebury Stone Circle. It has been voted one of the top picnic spots in England. Having a picnic lunch at close proximity of these ancient and mysterious stone structures will surely be unforgettable.
Take a trip to Stourhead gardens and spot places that were used in the filming of Pride & Prejudice. Lacock village is a beautiful place to go for a stroll with your lover, and experience the history that is lying here. The 14th century Salisbury Cathedral is also another must visit place with your lover.
If you want to relax after all these travelling, just go for a luxurious and relaxing spa couple therapy with your loved one, or visit one of Wiltshire’s award winning Michelin Star restaurants to indulge in an array of gourmet food and wine this place has to offer. With all these romantic places to visit, the beautiful food and the peaceful setting, Wiltshire will surely turn your romantic getaway into the perfect one.
The post PLAN THE PERFECT LITTLE ROMANTIC GETAWAY IN WILTSHIRE appeared first on Quirky Nomads.

domain: geography


The Yankees’ complaints that they believed the Astros were using technology to steal signs in this year’s ALCS didn’t stop after Game 1.
Sources confirmed the Yankees notified Major League Baseball about blinking lights in center field during Game 6 at Minute Maid Park, and the alleged blinking stopped later in the game.
It’s unclear if this would represent a rules violation, but it is something the league would look into if a team were trying to gain an advantage.
The MLB investigation into potential cheating by the Astros is ongoing and league officials declined to comment Wednesday following an initial report by SNY.
The Yankees’ issue with the outfield lights adds to the list of accusations levied at the Astros, which date back at least to their World Series victory in 2017. Houston lost to Washington in this year’s World Series.
The Astros were cleared of any wrongdoing regarding the allegations the Yankees made regarding Game 1 of this year’s ALCS after coaches became upset with a whistle coming from the Astros’ dugout. There is belief the whistling wasn’t being deployed as a sign-stealing tactic and instead was used to incite further Yankees…


DISABLED PARKING PERMIT
To receive a PERMANENT Disabled Parking Permit, an application MUST be completed and signed by a Medical Doctor (MD), Doctor of Osteopathy (DO), Physician Assistant (PA), Nurse Practitioner (NP), Doctor of Podiatric Medicine (DPM), or Optometrist (OD for blindness) must be brought to the Town Clerk’s Office.
- Bring in your expiring permit with Valid NYS driver’s license or non-Driver’s ID card is required
(If you are picking up the permit for someone else, you must bring both your license and the applicant’s license)
- No Fee
- PERMANENT Permits are valid for three (3) years
- No doctors note is required to renew a PERMANENT permit
TEMPORARY permits may be certified only by a Medical Doctor or Doctor of Osteopathy
- The doctor will authorize the valid time period on the application
SNOW PLOW PERMIT
Any person, firm or corporation that will have a vehicle plowing within the Town of Cheektowaga, outside the Village of Depew and Sloan, MUST have a permit issued by the Town Clerk’s office. The Owner of the vehicle is required to complete the proper form.
- Permit fee is $25 per vehicle
- Certificate of Insurance with evidence of liability insurance – (see Required Insurance)
- Permit is valid from October 1 thru April 30 of the following year and Non-Transferable
Any person who desires to operate a taxicab or taxicabs and/or livery owned or controlled by that person, upon the public highways with the Town, shall file a written application and provide the required forms and documents for review and approval


text:
The Biden administration supports murdering babies, and Archbishop Salvatore Cordileone wants to make it known that Biden is rejecting the teachings of the Church.
“San Francisco Archbishop Salvatore Cordileone warned that President Joe Biden not only dissents from Church teaching but also from ‘sound science’ when it comes to his enthusiastic support for abortion,” reported Breitbart News.
In an interview published by America Magazine, Archbishop Cordileone said President Biden, “seems to be more guided by the Democratic Party than his Catholic faith on the issues where we’re not in harmony.”
“Biden recently said that he no longer believes that life begins at conception, which violates basic embryology, the archbishop observed, since it’s not a matter of religious belief when life begins.”
“Science tells us life begins at conception. The church affirms that. So he is explicitly dissenting not only from Church teaching but from sound science,” the archbishop added.
The president of Southern Evangelical Seminary has joined the U.S. bishops in condemning Joe Biden’s extreme and aggressive pro-abortion agenda. https://t.co/BjjHKsAZC5
— Breitbart News (@BreitbartNews) February 10, 2021
“Since Roe, more than 60 million babies have been murdered in their mother’s wombs,” Cordileone said. “I mean, it’s a bloodbath, not to mention the mothers who have been harmed and dealing with those scars, those emotional scars and psychological scars, and very often are not allowed to even talk about it.”
“They’re feeling this hole, this anguish inside,” Cordileone added. “Those who say that they’re for women, their response is, ‘You’re not supposed to be feeling that.’ So then they have to bury it.”
Salvatore went on to talk about the options offered by the church to remedy the problem of abortion, and you can read about those options here.

domain: news


text:
EARLY CLOSING FROM 2PM ON MONDAY 20TH AUGUST FOR SUMMER STAFF PARTY.
Our menu runs all day every day. If you want breakfast at 2pm, find it at The Longholme!
Our display fridge in the cafe is ever-changing with alternative sandwiches, salads & sweet treats not shown here.
Fresh soft french stick with your choice of the below. Always British meats & free range eggs.
3 rashers, cooked how you like them
2 sausages, well seasoned and succulent
2 eggs fried how you like them
It's always better with an egg
Some signatures served all day, every day.
Fried herby potatoes with diced sausage & bacon served with a sunny free range egg.
Free range eggs whipped with crème fraiche.
Served on sourdough with chives.
Add bacon or smoked salmon - 1.60
On sourdough with beetroot hummus. Fresh tomato and onion salsa. Served with Virgin Mary shot. YUM!
A generous bowl of natural greek yoghurt with blueberries, granola & honey .
Locally baked sourdough served with with butter, jam or marmalade.
All our pancakes are gluten free, light and zesty!
With Maple syrup & icing sugar
With Greek yoghurt, lemon zest & honey.
With chocolate chips & chocolate sauce
Lightly toasted, served with house salad.
With roasted peppers, cream cheese & mixed herbs
British ham, cheddar cheese & Dijon mustard
With rich green pesto & sliced tomatoes
New for 2018 -
Quinoa, red cabbage, peppers, spring onion, sweetcorn & parsley served with a lemon dressing with your choice of topping:
A homemade blend of Mediterranean vegetables. Served with Swedish knäckebröd. Much better than just cold soup ;)
Organic & delicious, made with fresh cream, Suitable for vegetarians.Choose from Vanilla or chocolate.
A convenient and delicious cone available in white chocolate and caramel or raspberry and cream
Vanilla Flavour Ice Cream Dipped in Milk Chocolate with a Milk Flavoured Swirl.
Honeycombed Flavour Ice Cream Covered in Milk Chocolate with Popping Candy
Chocolate flavoured sandwich biscuits filled with vanilla flavour ice cream with crushed biscuit pieces with a vanilla flavour filling
Fruit Ice Lolly with 5 Fruit Flavoured Segments. No artificial colours, flavours or preservatives
Assorted fruit water ice push ups.
No artificial colours, flavours or preservatives. Suitable for vegetarians
Although every care is taken to prevent cross contamination
please be advised that food prepared on site may contain all known allergens.
Please advise a member of the management team when placing your order if anyone sufferers with food allergies for the best advice on our available products. Menu items may contain more than is listed.
Gluten free bread and dairy free milks are readily available. Vegan options are available.

domain: food


Technology giants that for years have waged a fiercely competitive battle against each other on the front lines of cyberspace are for the first time working together against a common foe - the U.S.government.
In response to last summer's revelations about the National Security Agency's snooping on Web surfers - and since then the endless disclosures of additional government spying on citizens here and abroad - the companies are mounting a campaign to curb the U.S.government surveillance programs. A coalition that includes Google, Apple, Yahoo, Facebook and Microsoft lashed out in an open letter printed Monday in major newspapers across the country and posted on a new website, http://reformgovernmentsurveillance.com.
"The balance in many countries has tipped too far in favor of the state and away from the rights of the individual -- rights that are enshrined in our Constitution. This undermines the freedoms we all cherish. It's time for a change," the companies wrote in the letter addressed to President Barack Obama and members of Congress. "We urge the U.S. to take the lead and make reforms that ensure that government surveillance efforts are clearly restricted by law, proportionate to the risks, transparent and subject to independent oversight."
The companies outlined five principles that the government should follow to protect the privacy of Internet users.
-- Limit governments' authority to collect users' information. This includes limiting surveillance to specific, known users for lawful purposes, and doing away with bulk data collection of Internet communications.
-- Greater oversight and accountability of intelligence agencies seeking to collect or compel the production of information. Reviewing courts should be independent and include an adversarial process, and governments should allow important rulings of law to be made public in a timely manner so that the courts are accountable to an informed citizenry.
-- Governments should allow companies to publish the number and nature of government demands for user information. In addition, governments should also promptly disclose this data.
-- Respect the free flow of information. Governments should permit the transfer of data and should not inhibit access by companies or individuals to lawfully available information that is stored outside of the country.
-- Avoid conflicts among governments by establishing a robust, principled, and transparent framework to govern lawful requests for data across jurisdictions.
In his own statement on the new website, Google CEO Larry Page said, "The security of users' data is critical, which is why we've invested so much in encryption and fight for transparency around government requests for information. This is undermined by the apparent wholesale collection of data, in secret and without independent oversight, by many governments around the world."
And Facebook CEO Mark Zuckerberg added, "Reports about government surveillance have shown there is a real need for greater disclosure and new limits on how governments collect information."
Of course, the motives of these billionaire CEOs are not completely altruistic. Protecting the privacy of their customers is paramount to protecting their own bottom lines. One of the reasons the technology companies have become a rich vein for crime-fighting authorities is that they routinely store vast amounts of personal data as part of their efforts to tailor services and target advertising, the Associated Press reports.
The NSA revelations have raised fears that people might shy away from some Internet services or share less information about themselves. Such a shift would make it more difficult for companies to increase their ad revenue and, ultimately, boost their stock prices.
The new principles outlined by the companies contain little information and few promises about their own practices, which privacy advocates say contribute to the government's desire to tap into the companies' data systems, notes a report from the New York Times.
"The companies are placing their users at risk by collecting and retaining so much information," Marc Rotenberg, president and executive director of the Electronic Privacy Information Center, told the Times. "As long as this much personal data is collected and kept by these companies, they are always going to be the target of government collection efforts."
However, there is a big difference between a company that collects information about its customers for advertising purposes, and government intruding in our private lives. As consumers we can choose to simply ignore the barrage of advertisements tailored to our habits and interests, but what choices do we have when government uses that same information in a sweeping surveillance program? There is something Orwellian and downright creepy about what the NSA has been doing.
Hopefully with the money and political clout of some of the country's richest CEOs now behind the fight against the NSA surveillance programs we will see some real reforms.


Main performance and structural features:
1. The product processing is self-contained, which significantly improves the sanitary conditions and significantly improves the production efficiency.
2, micro-computer automatic control, large-screen touch human-machine interface, parameter setting is convenient and fast
3, servo motor uninterrupted compensation, the bag length is set in one step, saving time and film, good finished product quality
4. The whole machine is compact in structure, stable in operation, stable in performance, easy to operate and convenient.
5, good sealing, good stability, high precision
Scope of application:
Forming container for toffee and bubble gum
The main technical parameters:
Square, rectangular, cylindrical
Package specifications (mm)
L20-120 W 12-20（φ8-φ13） H 6-12
Dimensions (L × W × H)


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|Sat 11 Feb - Sat 18 Feb|
Garter Lane Friends: €18.00
Sat 18 Feb SOLD OUT - returns only
The Hall by Pat Daly
*Running time: 75 mins, with no interval*
The Hall is a new stage play by Waterford playwright Pat Daly. It's the story of Joe whose life has all but crashed beneath his feet. Determined to rebuild his life, he struggles with the day to day minutia of living in a men's hostel. Alongside the other marginalised character; Skanger JP selling drugs, failed rapper Hip Hop's agoraphobia and what seems to be an unhealthy attraction to the wagon Roisin, the hostel manager. When Joe intervenes to teach JP a tough life lesson, it starts a chain of events that are devastating for him and those around him.
The Hall is in much the same vein as Pat's previous works, tragic-comic drama. His plays Urbs Intacta Manet, Dissident, GTi and John Roberts Square played to sold out audiences in Waterford city in the recent past. His play Urbs Intacta Manet made its UK premiere in London in November 2016 under the title Rigor Mortis. The Hall is set in a fictional men's hostel located in the city, in which a number of characters cross paths. This play has been rattling around in Pat's head for a few decades and has finally found its way to the page.

domain: literature


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Expression of Nrf2 and NF-κB transcription factors in breast cancer and breast fibroadenoma: Insights for a new therapeutic approach
Metrics: PDF 1020 views | Full Text 1630 views | ?
Camila Maria Simplicio-Revoredo1, Renato de Oliveira Pereira2, Mariella de Almeida Melo2, Pedro Vitor Lopes-Costa2,3, Paulo de Tarso Moura-Borges3, Emerson Brandão Sousa3, Fidelis Manes Neto2, Viriato Campelo2, Ione Maria Ribeiro Soares-Lopes2, Maria da Conceição Barros-Oliveira1, Cleciton Braga Tavares1, Alesse Ribeiro dos Santos3, Camila Guedes Borges de Araújo2, Eid Gonçalves Coelho1, Larysse Cardoso Campos-Verdes1, Aldenora Oliveira do Nascimento-Holanda2, Jackeline Lopes Viana3, Maria Liduina Meneses Bezerra-Chaves3, Rodrigo José de Vasconcelos-Valença2, Lina Gomes dos Santos1, Lauro Rodolpho Soares-Lopes2, André Luiz Pinho-Sobral3, Luiz Henrique Gebrim1 and Benedito Borges da Silva1,2,3
1 Postgraduate Program, Northeast Biotechnology Network (RENORBIO), Department of Health, Federal University of Piauí, Teresina, Piauí 64000-020, Brazil
2 Postgraduate Program in Health Sciences, Department of Mastology, Federal University of Piauí, Teresina, Piauí 64000-020, Brazil
3 Getúlio Vargas Hospital, Department of Mastology, Federal University of Piauí, Teresina, Piauí 64000-020, Brazil
|Benedito Borges da Silva,||email:||[email protected]|
Keywords: breast cancer; fibroadenoma; NRF2; NF-κB; immunohistochemistry
Received: November 25, 2019 Accepted: April 03, 2020 Published: May 05, 2020
Background: Cancer and fibroadenoma are the most common breast tumors in women of reproductive age. Nuclear factor erythroid 2-related factor 2 (Nrf2) and the nuclear factor kappaB (NF-κB) transcription factor play an important role in the inflammatory process and in cell proliferation. However, few studies have analyzed these markers in breast cancer and fibroadenoma in women of reproductive age.
Results: Light microscopy showed a higher concentration of anti-Nrf2 and anti-NF-κB-stained nuclei in breast cancer than in fibroadenoma. The mean percentage of stained nuclei for Nrf2 was 7.12 ± 5.2 and 43.21 ± 19.83 in the control and study groups, respectively (p < 0.0001). The mean percentage of anti-NF-κB was 10.75 ± 7.09 and 56.14 ± 21.19 (mean ± standard deviation) in the control and study groups, respectively (p < 0.0001). Histological grade 3 tumors showed a significantly higher expression of Nrf2 and NF-κB than grade 1 tumors (p < 0.05).
Material and methods: This study was approved by the Institutional Review Board of Federal University of Piaui and all patients assigned an inform consent term prior to the study initiation. Nrf2 and NF-κB expression was evaluated by immunohistochemistry in 66 patients, divided into two groups, control (fibroadenoma, n = 36) and study (cancer, n = 30). The data were analyzed using ANOVA test and the statistical significance was established at p < 0.05.
Conclusion: Nrf2 and NF-κB expression was significantly higher in breast cancer than in fibroadenoma, in addition to having a greater association with more aggressive tumors.
Breast cancer is the most commonly diagnosed malignant neoplasm in women worldwide and, although most prevalent in postmenopausal women, it is estimated that 4.8–5% of cases occur in young adults under 40 years of age . On the other hand, mammary fibroadenoma is the most common benign lesion in young women of reproductive age, being considered by some as not a tumor, but only an aberration of normal development and involution (ANDI) [2–3]. Despite some controversy over a higher risk for breast cancer in the presence of fibroadenoma, according to the concept of ANDI, this lesion may be considered as a control for breast cancer biomarker studies [4–8].
Despite early diagnosis through mammographic screening, and therapeutic advances, breast cancer is associated with high mortality, requiring a change in strategy when one therapy is ineffective . Changes in therapeutic strategy may be suggested by biomarkers, since alterations induced in biomolecular markers by the administration of drugs linked to the cell proliferation and apoptosis for shorter period of time (2 to 4 weeks) ocurr before any clinical response of the tumor to the treatment [9, 10]. Likewise, nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa B (NF-κB) transcription factor, related to cell proliferation and apoptosis are associated to malignant progression, poor prognosis and therapy resistance and thus may also suggest therapy changes [11, 12].
The Nrf2 pathway represents one of the most important cellular defensive mechanism against xenobiotic/electrophilic and oxidative stress, however the aberrant activation or accumulation of Nrf2 has recently been found to promote cancer development, progression and therapy resistance [11, 13]. There is increasing evidence to show the complexity of Nrf2 function, in addition to its antioxidant and detoxifying response, implicating it in many other molecular processes including inflammatory responses, metabolic reprogramming, cell proliferation, senescence and survival .
The NF-κB signaling pathway includes a family of transcription factors that play a role in immunity, inflammation and various cancers, including breast cancer . Activation of NF-κB leads to the induction of target genes that may inhibit apoptosis, interaction with cell cycle regulation, cell invasion, contribute to tumorigenesis, inflammation and metastatic growth, as well as resistance to radio and chemotherapy .
However, there are few studies evaluating the immunohistochemical expression of Nrf2 and NF-κB in women with breast cancer, and to the best of our knowledge no published research has simultaneously evaluated the expression of these biomarkers in women of reproductive age with breast cancer and fibroadenoma. This led us to design of the present study comparing Nrf2 and NF-κB expression in women of reproductive age with breast cancer and fibroadenoma.
The characteristics of both groups were homogeneous, except for age and waist circumference (Table 1). Distribution of breast cancer patients according to pathological characteristics showed in relation to the degree of histological differentiation of tumors, a predominance of histological grade 3, as well as the presence of breast tumors larger than 2 cm. Regarding the histological type, invasive ductal carcinoma was present in almost all patients diagnosed with breast cancer. The immunohistochemical profile showed that 50% of women with breast cancer had positive estrogen receptor (ER) and 50% had negative estrogen receptor, and there was a predominance of 56.7% for positive progesterone receptor (PR) and 80% negative for human epidermal growth factor receptor 2 (HER2). In addition, the luminal molecular subtype B was the most frequent, representing 53.3% of cases, followed by the triple negative subtype at 26.7% (Table 2). Light microscopy showed greater concentration of stained nuclei for Nrf2 and NF-κB in the study group compared to the control group (Figures 1 and 2). The mean percentage of stained nuclei for Nrf2 was 7.12 ± 5.20 and 43.21 ± 19.83 in the control and study groups, respectively (p < 0.0001). The mean percentage of stained nuclei for NF-κB was 10.75 ± 7.09 and 56.14 ± 21.19 in the control and study groups, respectively (p < 0.0001) (Table 3). Furthermore, Nrf2 expression was significantly higher in histological grade 3 tumors than grade 2 and grade 2 significantly higher than grade 1, while NF-κB expression was significantly higher in histological grade 3 tumors than in grade 1 (p < 0.05) (Figures 1 and 2). The box plot in Figures 3 and 4 clearly shows an increase in the mean percentage of histological grade 3 tumors than grade 1.
Table 1: Patient characteristics
|Characteristic||Control group (Fibroadenoma) (n = 36) Mean ± DP||Study group (Breast cancer) (n = 30) Mean ± DP||p value|
|Age (y)||32.92 ± 9.46||40.37 ± 6.77*||0.0011|
|Menarche age (y)||12.86 ± 1.16||13.67 ± 1.79||0.0820|
|BMI (kg/m2)||24.20 ± 4.61||25.70 ± 3.62||0.1540|
|WC (cm)||79.40 ± 12.34||83.92 ± 8.92*||0.0480|
Table 2: Distribution of breast cancer patients according to pathological characteristics
|Pathological features||Breast cancer|
|< 2 cm||12||40|
|≥ 2 cm||18||60|
|Ductal in situ||01||3.3|
|Hormone receptor status|
Figure 1: Photomicrographs of histological sections of breast fibroadenoma (A), histological grade 1 breast cancer (B), grade 2 breast cancer (C) and grade 3 breast cancer (D). Note the higher concentration of Nrf2 stained nuclei in breast cancer cells compared to fibroadenoma cells and also a higher concentration of Nrf2 stained nuclei in histological grade 3 than grade 2 and higher in grade 2 than grade 1 breast cancer (original magnifcation × 400).
Figure 2: Photomicrographs of histological sections of breast fibroadenoma (A), histological grade 1 breast cancer (B), grade 2 breast cancer (C) and grade 3 breast cancer (D). Note the higher concentration of NF-κB stained nuclei in breast cancer cells compared to fibroadenoma cells, and also a higher concentration of NF-κB stained nuclei in histological grade 3 than grade 1 breast cancer (original magnifcation × 400).
Table 3: Mean percentage of cases with cells expressing Nrf2 and NF- κB in the control group (fibroadenoma) and study group (breast cancer)
|Control group (Fibroadenoma) (n = 36) Mean ± DP||Study group (Breast cancer) (n = 30) Mean ± DP||p value|
|Nrf2||7.12 ± 5.20||43.21 ± 19.83*||0.0001|
|NF-κB||10.75 ± 7.09||56.13 ± 21.19*||0.0001|
Figure 3: Nrf2 expression in diferent histological grades of breast cancer: mean percentage of Nrf2 expression was significantly higher in histological grade 3 tumors than grade 2 and significantly higher in grade 2 than grade 1 (p < 0.05).
Figure 4: NF-κB expression in diferent histological grades of breast cancer: mean percentage of NF-κB expression was significantly higher in histological grade 3 tumors than in grade 1 (p < 0.05).
There is evidence that Nrf2 and NF-κB are good biomarkers due to their high expression in invasive breast carcinoma cells. However, few studies have attempted to elucidate the behavior of these proteins in fibroadenoma, a benign tumor that does not increase the risk of developing breast cancer [15, 16]. This feature makes fibroadenoma an ideal control for determining the expression effect of these proteins on breast cancer and the prognosis in breast cancer.
In the present study, significant overexpression of Nrf2 was observed in breast cancer tissue cells compared to fibroadenoma. To date, only Onodera et al. have investigated Nrf2 expression in human breast fibroadenoma . These authors evaluated 24 women with benign breast lesions, including papilloma, sclerosing adenosis, usual ductal hyperplasia, and fibroadenoma, and found that Nrf2 was positive only in one case of fibroadenoma (4%) while it was positive in 44% of the women with breast carcinoma. Furthermore, the authors showed that the status of Nrf2 immunohistochemistry in women with mammary carcinoma correlated positively with histological grade, Ki-67 labeling index, p62 immunoreactivity, nicotinamide adenine dinucleotide cofactor NAD(P)H immunoreactivity, and quinone oxidoreductase 1 (NQO1). Similarly, in our study, Nrf2 activation was significantly associated with high histological grade. Therefore, Nrf2 overexpression may be an adverse prognostic factor for both relapse and disease-free survival of patients.
NF-κB overexpression was also significantly observed in breast cancer tissue cells compared to fibroadenoma. Based on our literature search, only Sarkar et al. has previously investigated the expression of NF-κB in human breast fibroadenoma . According to these authors, NF-κB was undetectable in control group breast tissue patients, whereas activation of NF-κB was significantly correlated with high grade, large tumor size, high NPI value, ER negativity, PR negativity and HER-2/neu positivity in breast cancer patients.
Overexpression of NF-κB implies aggressive tumor biology in breast cancer and may predict tumors with a likely unfavorable prognosis . In our study, NF-κB activation was significantly associated with high histological grade corroborating the findings of Sarkar et al. and Shapochka, Zaletok and Gnidyuk [15, 17]. Thus, considering that breast cancer in young women commonly has a higher histological grade, as well as an unfavorable hormonal status, and a higher overall mortality rate compared to older women, the application of NF- κB as a biomarker may be a promising target for prognosis and therapy of malignant tumors in women of reproductive age [17, 18].
In our study, it is noteworthy that although the control (fibroadenoma) and study (breast cancer) groups of women were of reproductive age, the average age of women with breast cancer was significantly higher when compared to those with fibroadenoma. Studies show that breast cancer occurs more often in older women, while fibroadenoma is more common in younger women [19, 20]. In addition, the measured waist circumference was higher in women with breast cancer than in those with fibroadenoma, which increases the risk of cancer-related metabolic complications and contributes to a worse prognosis .
Based on the results of this study, a new therapeutic approach emerges in breast cancer, since overexpression of Nrf2 and NF-κB is associated with malignant cells with a higher histological grade and, thus, inhibition of expression of these factors may provide a promising strategy in the treatment of these patients. This builds evidence for the need to conduct intervention studies that evaluate the relationship between inhibition of Nrf2 and NF-κB transcriptional pathways and the prognosis of women with breast cancer.
Materials and Methods
This study was approved by the Internal Review Board of the Federal University of Piaui (CAAE: 43447015.8.0000.5214). All patients signed a written informed consent form before study initiation. In addition, we confirm that all methods were performed in compliance with current Brazilian laws, in conformity with ethical standards of institutional and national research committees, following the 1964 Helsinki Declaration and its later amendments. A transversal study was carried out, involving 75 premenopausal women with breast tumors. Patients were recruited at the Mastology Clinic of the Getúlio Vargas Hospital, Federal University of Piauí, Brazil, from October 2014 to October 2016. Nine patients were excluded due to technical problems that precluded analysis. Patients were divided into two groups, control group (fibroadenoma, n = 36) and study group (breast cancer, n = 30). All study participants underwent a specialized surgical procedure for histologic and immunohistochemical confirmation of the tumor. The study included premenopausal patients with levels of follicle-stimulating hormone (FSH) < 30 mUI/ml, fibroadenoma or carcinoma of the breast and no previous oncologic treatment.
Breast tissue samples fixed in buffered formalin were cut into 3 μm-thick sections. Sections were deparaffinized in xylol for 5 minutes, dehydrated in absolute ethanol, washed in buffered saline solution at pH 7.4 for 5 minutes and then treated for 5 minutes with 3% hydrogen peroxide (H2O2) in buffered solution to block endogenous peroxidase activity. For antigen retrieval, the slides were placed in racks containing 0.21% citric acid (pH 6.0) and heated in a microwave oven for 15 minutes at maximum power. The slides were cooled, and phosphate-buffered saline was added for a cooling period of 20 minutes. Tissue samples were incubated overnight at 4–8°C with Anti-Nrf2 rabbit polyclonal antibody (1: 100 dilution) and with anti-NF kappa B / p65 rabbit polyclonal antibody (1: 100 dilution), separately. The slides were rinsed with PBS-Tween and incubated with secondary antibody (anti-mouse BA 2000, Vector Laboratories, Burlingame, CA, USA) for 30 minutes at room temperature. After being washed again with PBS-Tween, the slides were incubated with reagents from the ABC Elite detection system (PK 6100, Vector Laboratories) for 45 minutes at room temperature. The samples were rinsed once more with PBS-Tween and incubated with DAB (1.0 ml EnVision FLEX DAB for one drop of chromogen) and for 5 minutes. Finally, the slides were washed with distilled water, counterstained with hematoxylin, stained with ammoniacal solution, dehydrated with absolute ethanol, passed through Coplin jars containing xylol and mounted in Permount resin. Cells expressing Nrf2 and NF-κB proteins were identified by dark brown staining in the nucleus.
Two observers, who were blinded with respect to the patients’ identity and had no previous knowledge of any of the cases, performed quantification. It was carried out using a light microscope (Nikon Eclipse E-400, optical microscope, Tokyo, Japan) connected to a color video camera (Samsung digital camera CHC-370 N, Seoul, Korea), which captured the image and transmitted it to a computer equipped with the Imagelab® software program, version 2.3 (Softium Informatica Ltda, Sao Paulo, Brazil) for image analysis.
To determine Nrf2 and NF-κB expressions, we counted nuclei of stained cells under a microscope with a magnification of 400X. At least 600 cells of the breast epithelium were counted on each slide, in random fields, starting in the area of highest Nrf2 and NF-κB concentration in the cell nucleus, using Processing Software and Image Analysis-Image Lab® (SOFTIUM Informatica Ltda, São Paulo, Brazil). The percentage of stained cells for each case was obtained from the ratio between the number of cells with stained nuclei and unstained nuclei multiplied by 100 (labelling index).
Data were analyzed using SPSS statistical program for Windows 18.0. Data were expressed as frequencies, percentages, measures of central tendency and dispersion. The normality of the data was tested with the Kolmogorov-Smirnov test. The Levene test was used to verify data homogeneity. To compare more than two means between normal and homogenous data, we used Student’s t-test and ANOVA. Significant levels were set at p values ≤ 0.05.
This study was approved by the Internal Review Board of the Federal University of Piaui (CAAE: 43447015.8.0000.5214). All patients signed a written informed consent form before study initiation.
The authors thank the patients who participated in the current study and the Postgraduate Program of the Federal University of Piauí, Brazil.
CONFLICTS OF INTEREST
The authors declare that they have no competing interests.
This study was not funded.
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2. Ciurea AI, Herţa HA, Iacoban CG, Fetica B, Rogojan L, Ciortea CA. Fibroadenomas and breast carcinoma: a possible answer to a frequently asked question. A pictorial essay. Med Ultrason. 2018; 20:385–91. https://doi.org/10.11152/mu-1408. [PubMed].
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6. Nassar A, Visscher DW, Degnim AC, Frank RD, Vierkant RA, Frost M, Radisky DC, Vachon CM, Kraft RA, Hartmann LC, Ghosh K. Complex fibroadenoma and breast cancer risk: a Mayo Clinic Benign Breast Disease Cohort Study. Breast Cancer Res Treat. 2015; 153:397–405. https://doi.org/10.1007/s10549-015-3535-8. [PubMed].
7. Worsham MJ, Raju U, Lu M, Kapke A, Botttrell A, Cheng J, Shah V, Savera A, Wolman SR. Risk factors for breast cancer from benign breast disease in a diverse population. Breast Cancer Res Treat. 2009; 118:1–7. https://doi.org/10.1007/s10549-008-0198-8. [PubMed].
8. Sampaio FA, Martins LM, Dourado CS, Revoredo CM, Costa-Silva DR, Oliveira VA, Alves-Ribeiro FA, Silva BB. A case-control study of Metallothionein-1 expression in breast cancer and breast fibroadenoma. Sci Rep. 2019; 9:7407. https://doi.org/10.1038/s41598-019-43565-0. [PubMed].
9. Dowsett M, Smith IE, Ebbs SR, Dixon JM, Skene A, Griffith C, Boeddinghaus I, Salter J, Detre S, Hills M, Ashley S, Francis S, Walsh G, A’Hern R. Proliferation and apoptosis as markers of benefit in neoadjuvant endocrine therapy of breast cancer. Clin Cancer Res. 2006; 12:1024s–30s. https://doi.org/10.1158/1078-0432.CCR-05-2127. [PubMed].
10. Lopes-Costa PV, dos Santos AR, dos Santos LG, da Silva BB. Evaluation of Ki-67 and Bcl-2 antigen expression in breast carcinomas of women treated with raloxifene. Cell Prolif. 2010; 43:124–29. https://doi.org/10.1111/j.1365-2184.2009.00664.x. [PubMed].
12. Sarkar DK, Jana D, Patil PS, Chaudhari KS, Chattopadhyay BK, Chikkala BR, Mandal S, Chowdhary P. Role of NF-κB as a Prognostic Marker in Breast Cancer: A Pilot Study in Indian Patients. Indian J Surg Oncol. 2013; 4:242–47. https://doi.org/10.1007/s13193-013-0234-y. [PubMed].
14. Zhang HS, Du GY, Zhang ZG, Zhou Z, Sun HL, Yu XY, Shi YT, Xiong DN, Li H, Huang YH. NRF2 facilitates breast cancer cell growth via HIF1α-mediated metabolic reprogramming. Int J Biochem Cell Biol. 2018; 95:85–92. https://doi.org/10.1016/j.biocel.2017.12.016. [PubMed].
15. Chang J, Zhang Y, Li Y, Lu K, Shen Y, Guo Y, Qi Q, Wang M, Zhang S. NrF2/ARE and NF-κB pathway regulation may be the mechanism for lutein inhibition of human breast cancer cell. Future Oncol. 2018; 14:719–26. https://doi.org/10.2217/fon-2017-0584. [PubMed].
16. Onodera Y, Motohashi H, Takagi K, Miki Y, Shibahara Y, Watanabe M, Ishida T, Hirakawa H, Sasano H, Yamamoto M, Suzuki T. NRF2 immunolocalization in human breast cancer patients as a prognostic factor. Endocr Relat Cancer. 2014; 21:241–52. https://doi.org/10.1530/ERC-13-0234. [PubMed].
17. Shapochka DO, Zaletok SP, Gnidyuk MI. Relationship between NF-κB, ER, PR, Her2/neu, Ki67, p53 expression in human breast cancer. Exp Oncol. 2012; 34:358–63. [PubMed].
18. Erić I, Petek Erić A, Kristek J, Koprivčić I, Babić M. Breast cancer in young women: pathologic and immunohistochemical features. Acta Clin Croat. 2018; 57:497–502. https://doi.org/10.20471/acc.2018.57.03.13. [PubMed].
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20. Martins LM, de Melo Escorcio Dourado CS, Campos-Verdes LM, Sampaio FA, Revoredo CM, Costa-Silva DR, da Conceição Barros-Oliveira M, de Jesus Nery Junior E, do Rego-Medeiros LM, Gebrim LH, Alves-Ribeiro FA, Rodrigues GP, Chagas DC, et al. Expression of matrix metalloproteinase 2 and 9 in breast cancer and breast fibroadenoma: a randomized, double-blind study. Oncotarget. 2019; 10:6879–84. https://doi.org/10.18632/oncotarget.27347. [PubMed].
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domain: medical


text:
Every superhero has an origin story! Let the world know yours with the Sideshow ‘Raised By Comics’ T-Shirt. The vibrant logo is bursting with comic book action, perfect for fans of four-color fiction.
This comfortable black Next Level brand CVC crew shirt features a yellow caption with the words “Raised by…” and the word “COMICS” filled in with yellow, blue, and red screentone to capture that classic comic feel.
© Sideshow 2019
I love this design. I have three of them, two XL and one L. I bought my girlfriend one (XS) 😉 and she loves it. We wear them sometimes when we go out together and we always get compliments on the shirts.

domain: design


text: The China National Offshore Oil Company (CNOOC; CEO.NYSE) reported that first-half profits surged 51.4% year-on-year to US$5.16 billion, state media reported. The country’s largest offshore oil producer reported a 12.9% increase in production, boosted by new oilfields coming online. Earnings per share were US$0.14, and a pretax dividend of US$0.03 per share was proposed. The company’s realized oil price for the first half was US$108.16 per barrel, up 40.8% from a year earlier, which helped to boost revenues by 45% to US$15.18 billion. At the same time the company was able to reduce operating costs by 3.8%. However, CNOOC reduced net production targets for 2011 following recent oil spills in Bohai Bay on a point-venture oil field with ConocoPhillips (COP.NYSE).

domain: economics


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Medical College of Wisconsin: first successful treatment of CART patient and use of Miltenyi’s CliniMACS Prodigy®
The Medical College of Wisconsin has published a press release reporting on their first successfully treated CART patient and how they used Miltenyi’s CliniMACS Prodigy®.
Physicians and researchers from the Medical College of Wisconsin (MCW), Froedtert Hospital, Children's Hospital of Wisconsin, and BloodCenter of Wisconsin have successfully used a new immunology treatment, chimeric antigen receptor (CAR) T-cell therapy, to extend the life of a 52-year-old Wisconsin man.
While CAR-T cell therapy has been under development since 2012, the patient treated at Froedtert & the Medical College of Wisconsin Clinical Cancer Center is the first patient to participate in the first-ever, clinical trial for a novel dual-targeted CAR-T cell against CD19 and CD20 that were manufactured using the CliniMACS Prodigy® device, which is part of an automated CAR-T cell manufacturing platform developed by Miltenyi Biotec, a global company dedicated to enabling cellular and gene therapies. The modified cells can identify cancerous cells, attach to the cancer cells, and effectively destroy the cancer cells. A separate pediatric clinical trial for CAR-T treatment at Children's Hospital of Wisconsin is expected to start later this year.
The full press release is available here.

domain: health


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San Diego Mayor Kevin Faulconer: Local Police Will Not Act As Immigration Agents
Friday, March 17, 2017
Kevin Faulconer, mayor, City of San Diego
Memo: Delegated Authority Program
In a memo issued to the San Diego City Council Mayor Kevin Faulconer said San Diego will maintain its long-standing tradition of police not initiating, "contact for the sole purpose of checking an individual's immigration status."
To view PDF files, download Acrobat Reader.
In response to an inquiry from the San Diego City Council, Mayor Kevin Faulconer gave his clearest indication yet that the city will not participate in any attempt to deputize local law enforcement officers as Immigration and Customs Enforcement agents.
An executive order signed by President Donald Trump in January seeks to renew a national security policy that gives local police and sheriff's deputies authority to act as immigration agents and arrest undocumented immigrants.
In a memo issued to the council on Wednesday, Faulconer said San Diego will maintain its long-standing tradition of police not initiating "contact for the sole purpose of checking an individual's immigration status."
Faulconer joined Midday Edition Friday to discuss the city's position on this issue.
Q. Is this stand against police acting as Immigration and Customs Enforcement, or ICE, agents a position the city is taking on principal, or for practical reasons?
A. Well, it’s a long standing policy that has served our city very, very well on both issues. Look, it’s very important that we have, and we do have, one of the safest big cities in the country. And the agreement that we’ve had ensures that he have not just safe communities, but we have the trust of individuals in neighborhoods. If you’re the victim of a crime, we want you to speak with our police officers. If you’re a witness to a crime, we want you to be able to speak with our police officers and not fear any other repercussions or recourse. It’s a policy that has worked very well for us over a number of years and, you know, Republican administrations, Democratic administrations, it’s just the right thing to do.
Q. You make clear in your memo that local law enforcement will continue to notify ICE of the immigration status of someone who gets booked into jail. Is that what you believe separates San Diego from a sanctuary city?
A. It is. Because, look, we have what we consider to be the right balance and again a balance that serves us very well in terms of safety. In terms of interaction with the community. In our philosophy of community policing, it’s essential that you have the trust of your community and neighborhoods and that’s something that our department has worked very, very hard on over that last several years, particularly the last decade. So, we want to continue that trust. It is something that has worked very, very well for us here in the city of San Diego and frankly, I think it's a policy that other cities can emulate.
Q. The reason the city council asked for clarification on this policy is because of the level of concern among many residents in San Diego. Have you personally heard from constituents on this issue about their concern of local law enforcement basically being turned into immigration agents?
A. It is a topic that has been in the news and certainly at community groups and other meetings. I think it's important for us as a city, one of the reasons that I wrote the memorandum, to reinforce what our policy has been and why it works and to continue that trust and to continue that support of our community and it is one, as I said, that is essential that has kept us one the safest big cities in the country.
Q. Do you have concerns about the recent immigration sweeps in Los Angeles?
A. I think every community is going to have to deal with its own issues in terms of interaction, not just locally but with the federal government. I think one of the things that’s important to us here in the region, is the strong support that we have, not just at the local level with our police department and our sheriff’s department, but the fact that we do work with our federal partners in terms of making sure that he have safe and secure communities. And it’s very important to me, part of the reason again why I wrote this memorandum, that we talk about what the primary focus is of our law enforcement and our police department ensure that we keep everybody safe. We’re fostering those partnerships between law enforcement and our neighbors and we’re saying to folks that there is a role for the police department, but it's not to become ICE officers.
Q. The president released his budget yesterday and among many other things, it eliminates Community Development Block Grants which are frequently used for projects in low-income areas of San Diego. What impact do you think that will have?
A. I will tell you that the CDBG grants are very important to us in San Diego. Not just for us here, but in cities across the state and indeed across the country. We utilize those for a variety of important programs, just like we use housing funds for a lot of our housing affordability and affordable housing. So, when we look at making sure our voice is heard at the federal level, particularly on the budget, strongly supporting the work that CDBG does and these HUD grants do is something that I am going to be very, very strongly supportive of continuing.
Q. Have you decided whether you’re going to run for governor next year Mayor Faulconer?
A. Maureen, I love exactly what I’m doing which is continuing to serve as mayor of this city and it’s an honor and a privilege and I’m looking forward to serving my entire four years.
Q. OK, so that’s a no?
A. I’m doing exactly what I’m doing.
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domain: law


SECRETARY ARSENIO M. BALISACAN
Socioeconomic Planning Secretary and
PHILIPPINE ECONOMIC BRIEFING
“Accelerating Infrastructure Development”
30 September 2014, 8:00 AM
Philippine International Convention Center, Pasay City
Infrastructure development remains one of the top priorities of the Philippine Government to help sustain the robust economic performance and the improved confidence level among the international business communities that the country is currently enjoying. As we know, infrastructure development plays a critical role in the growth and competitiveness of the Philippines and its major economic sectors; in reducing poverty, and creating quality employment; and in ensuring the safety of people, communities, properties and livelihood in times of natural disasters and calamities. Given all these, the government is working to enhance the quality, adequacy and accessibility of the country’s infrastructure.
The overall strategy of the government to accelerate infrastructure development is to increase public infrastructure spending from 2.2 percent of GDP in 2012 to at least 5.0 percent by 2016.
The strategies and action plans in the Philippine Development Plan are translated into priority programs and projects under the current Public Investment Program (PIP) being implemented within the medium-term by the national government (NG), government-owned and/or -controlled corporations (GOCCs), government financial institutions (GFIs), and other government offices and instrumentalities.
For 2013-2016, the priority programs and projects for the infrastructure sector consist of 952 projects with total investment requirements amounting to about USD46.69 billion (PhP2.06 trillion), including capital infrastructure projects, both ongoing and proposed.
This slide provides the breakdown for the subsectors until 2016.
Investment requirements for infrastructure development remain huge despite increased public infrastructure spending. Therefore, infrastructure development will be supplemented by private sector investments through Public-Private Partnerships (PPPs).
To optimize public-private partnerships and enhance the country’s attractiveness to private sector investors, the government has reviewed, amended, and approved policies and legal framework involving private sector participation, such as the IRR of the BOT Law (RA 7718) and the JV Guidelines. Reforms in the energy sector have also increased private sector participation. In July 2012, the Energy Regulatory Commission (ERC) approved the feed-in-tariff (FiT) rates to encourage RE developers to invest at the initial stage and hasten RE deployment.
To improve competitiveness and geographic connectivity, the Pocket Open Skies Policy (EO 29) was issued in 2011, allowing foreign carriers to operate unilateral and unlimited traffic rights to airports other than the Ninoy Aquino International Airport (NAIA). Meanwhile, the Common Carriers Tax (CCT) Act (RA 10378) aims to enhance the country’s competitiveness in international travel by encouraging international air carriers to include the Philippines in their primary routes.
Alongside these policies, the government is pursuing the synchronization of planning, programming and budgeting to ensure that the programs and projects are aligned with the country’s developmental goals and outcomes.
Sustaining the economy’s high-growth trajectory requires continued investment in infrastructure to unleash the potentials of many areas throughout the country. Thus, investors are encouraged to participate in the construction and implementation of various programs and projects that have been identified in a number of infrastructure-related roadmaps and master plans approved by the government. Several programs and projects in these roadmaps and master plans have no identified financing yet.
For transport infrastructure, priorities include the implementation of:
- The Transport Infrastructure Development Roadmap for Metro Manila and its Surrounding Areas (Region III and IV-a), to improve coordination among relevant agencies on transport projects in Metro Manila and its environs in the short-term, medium-term, and long-term;
- The Logistics Infrastructure Roadmap for Mindanao, to improve logistics infrastructure for cost-effective linking of Mindanao’s agriculture and fishery production centers to markets within the region, the rest of the country and abroad; and
- The DPWH and Department of Tourism (DOT) Convergence Plan, to provide road access to designated priority tourism destinations under the National Tourism Development Plan (NTDP).
Other approved infrastructure master plans include: The Flood Management Master Plan for Metro Manila and Surrounding Areas and the E-Government Master Plan (EGMP).
In the energy sector, the 2013-2017 Household Electrification Development Plan (HEDP) issued by the Department of Energy (DOE) sets the plans and strategies to attain 86.2-percent household electrification by 2016 and 90-percent by 2017, while the Philippine Energy Plan 2012-2030 targets 100-percent electrification of sitios by 2015.
To promote energy conservation and energy efficient technologies, the Department of Energy (DOE) is implementing various activities under the National Energy Efficiency and Conservation Program (NEECP), while the National Renewable Energy Program (NREP) aims to develop specific RE technologies and help the country triple its renewable energy capacity by 2030.
In terms of basic infrastructure facilities and services, the government is working to provide clean and safe drinking water to 14 million Filipinos; construct additional 87,034 classrooms by end of 2016; provide 262,287 socialized housing units from 2014 to 2016; construct, rehabilitate and upgrade 12,295 basic health care hospitals and facilities from 2014 to 2016; and improve solid waste and wastewater management.
For ICT, the adoption of the Integrated Services Digital Broadcast-Terrestrial (ISDB-T) or the Japanese standard in Digital Broadcasting provides potential investment opportunities for the development of Digital Terrestrial Television (DTT) broadcast infrastructure in the country.
As we accelerate infrastructure development, the government shall continue implementing strategies to improve the country’s business climate and encourage private sector participation through good governance, vital infrastructure support, and policy reforms to facilitate doing business in the country.


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Krill Oil by Regen Health formula harnesses the power of natural extracts to improve your heart health, lower cholesterol levels, improve joints, and promotes healthy aging.
- Lower Cholesterol Levels
- Enhanced Cardiovascular Health
- Improved Joint Maintenance
- Better Immune Function
- Anti-Aging Benefits
Effectively eases symptoms of arthritis by reducing joint pain and inflammation, as well as lowers blood pressure and maintains cholesterol levels.
Improves blood circulation throughout the body and maintains overall heart health, preventing the onset of cardiovascular diseases.
Functions as a detoxifier that promotes a pure and functioning liver, and strengthens the immune system, preventing the risk of chronic diseases and infections.
As seen on
When Does Krill Oil Work?
You'll start to feel the effect kicks in in just 20 minutes. You'll notice painful knees or joints starting to go away. You'll feel calmer & relaxed as your blood pressure starts to normalize.
You'll wake up in the morning without any pain or stiffness. You'll be full of energy, inspired, and feeling positive. You'll start enjoying deeper, more restful sleep.
You'll feel clean, smooth energy and focus during the day WITHOUT the crash. You'll enjoy a better mood and be more positive, without all the ups and down. You'll notice your joints don't ache anymore from normal daily activity.
THIRD MONTH AND BEYOND
You won't have to worry about 'forgetting' things anymore. You'll be motivated, in high spirit, and full of energy. You don't have to deal with fatigue, moody, and cranky all the time.
Unique Krill Oil Ingredient Matrix
A good source of DHA and EPA (Omega-3 fatty acids); offers many health benefits including easing joint pain and inflammation, improving blood circulation and cardiovascular health, aiding in the healthy digestion process, boosting immunity, and supporting cognitive function.
Lowers blood pressure, reduces inflammation, improves immunity, prevents heart disease, regulates mood, and fights symptoms of depression and anxiety.
Frequently Asked Questions
KRILL OIL is intended for people who are looking for a natural solution to improve heart health, lower cholesterol levels, improve joints, and promote healthy aging.
KRILL OIL is a potent solution that will work as soon as you use it. You’ll start to feel your joints ache or pain go away within 20 minutes of consuming this supplement. You’ll also feel calmer & relaxed as your blood pressure starts to normalize.
KRILL OIL and other products by Regen Health are totally safe. It is formulated with all-natural and FDA approved ingredients, created in a GMP certified facility in the USA. CAUTION: Pregnant or nursing mothers, children under the age of 18, and individuals with a known medical condition should consult a physician before using this or any dietary supplement.
As a dietary supplement, take one (1) softgel twice a day. For best results take 20-30 minute before meals with an 8 oz glass of water or as directed by your healthcare professional.


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How many confirmed coronavirus cases are there in Afghanistan?
There have been 58,037 confirmed cases of the novel coronavirus (COVID-19) in Afghanistan so far.
How many coronavirus (COVID-19) deaths have there been in Afghanistan?
There have been 2,549 deaths related to COVID-19 in Afghanistan so far.
How many patients have recovered in Afghanistan?
There are 52,242 patients in Afghanistan that have recovered from the virus.


text:
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Vaccines have emerged as the most effective method of protection to combat COVID-19. If you do get infected with the virus after getting the vaccine, the chances of serious effects are reduced. However, vaccines that have been accredited, which are tested very carefully for safety and efficacy, should only be administered by authorized personnel.
When you go to get vaccinated, you should understand the expected side effects and make the protection methods a part of your life before and after getting the vaccine. Here are some tips by Rohit Shelatkar, VP, Vitabiotics, health and nutrition expert, that will help you in the days after getting vaccinated.
As your body builds up its immunity, you should be prepared for some minor side effects. These side effects may last for a day or two. These include pain and redness at the injection site, chills and mild fever, body aches, headache and feeling tired. As per the doctor’s advice, you should take paracetamol or any other fever medicine.
- Too much stress can reduce the effectiveness and effectiveness of the vaccine. Calming exercises, meditation and aromatherapy are recommended. Do breathing exercises regularly.
- After taking the vaccine one should not smoke and drink alcohol at all. Smoking is known to reduce the effectiveness of the immunosuppressant elements of many vaccines. The same thing applies to alcohol as well.
- Drink plenty of fluids and do not let your body become dehydrated after taking a dose of the vaccine. Any kind of excessive exercise should be avoided for at least two days. The body needs time and exercising too much can lead to fatigue.
- A nutritious diet is important before and after taking the vaccine. Eat green vegetables, such as greens, spinach, broccoli, which are high in antioxidants. Doctors say that these things can help in combating the swelling that occurs after taking the vaccine. Contains Zinc, Vitamins C, B12, D and A. These are readily available in chickpeas, legumes (different types of beans like cowpea) and lentils, which help the body fight COVID better and also help the vaccine work properly.
- Consuming the right amount of protein helps ensure that the impact on your energy levels is minimal. Include adequate amounts of protein-rich foods like paneer, chicken, eggs, fish and kidney beans. It is best that you include some form of protein in all your major meals.
- Be patient. Do not panic if you see too many symptoms. The effects of the vaccine are normal and expected. In most cases, they go away on their own within a few days. Keep consulting the doctor from time to time and have faith in the vaccine.
As we saw in the second wave, we cannot take this COVID pandemic lightly. Worldwide, vaccines have emerged as the most effective way to deal with its severity. After taking the vaccine, our tips will help you deal with its effects. So get the vaccine and be safe!
Also read: 6 Pregnancy Problems And Their Home Remedies
Photo Courtesy: Freepik


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An MCC allows the homebuyer to claim up to $2,000 annually as a tax credit toward their federal income tax liability. These 2 programs may be combined to maximize the benefit to the homebuyer. To apply for either or both programs, contact a participating lender near you. Or, learn more about these exciting first time homebuyer programs.
More than half (56%) who prefer renting over buying say they don’t have the money to buy, 24% say they don’t want the financial commitment, and 22% say they have bad credit. the best investment.
In many cases, it’s not easy to be approved for a conventional home loan. As a first-time homebuyer with bad credit, As a first-time homebuyer with bad credit, you’re not at a dead end. You may be surprised what you qualify for with the FHA loan option at The Wood Group of Fairway Independent Mortgage Corporation.
State-by-state home buyer programs. On the map below, click on your state to see home buyer assistance programs available in your area. Once clicked, below the map you will find brief descriptions of available programs and a table of links to reach the state agency website, find participating lenders, see qualification details, get homebuyer education courses and to contact the agency for.
10 Percent Down Mortgage Loans Our 5% down payment Jumbo loan is a 10/1 ARM Q: Do you have other low down payment options? Buyers with 10% down or more will find more options. 10% is a popular options because of our 30 year fixed program.Good Banks To Get A Mortgage From The March 2019 Chartbook from the Urban Institute’s housing finance policy center has good news for you. off seeking loans from non-bank lenders, and non-bank lenders are driving the downward trend.
Some things in life can be both exciting and terrifying, all at the same time. Buying your first home, for example, is certainly exciting – but that six-figure debt most decidedly is not exciting; at least, not in a good way.. And, unfortunately, when you’re trying to buy your first home while also dealing with bad credit, the exciting-terrifying scale can start to tip all the more toward.
Tips for first-time homebuyers with bad credit. While first-time homebuyers with bad credit face more challenges than buyers with excellent credit, there are several steps you can take to demonstrate that you are a creditworthy borrower. Talk to a housing counselor.
Non Traditional Mortgage Financing This attractive jumbo mortgage is designed for those who are unable to secure a traditional home loan. It features generous guidelines such as alternative income qualification, low down payments, financing up to $3 million, and interest-only options.
Attend a homebuyer education course if you are a first-time homebuyer. If you are a first-time homebuyer, and have been pre-qualified, you must attend a homebuyer education course. This education will help you understand the importance and responsibilities of homeownership. In order to obtain a CalHFA home loan, your loan officer must produce.

domain: finance


text:
Jaki ojciec, taki syn. Opowieść o obrazach Pietera Brueghla Młodszego ze zbiorów Muzeum Narodowego w Krakowie
The Royal Castle in Niepołomice, called the second Wawel due to its striking resemblance to the Royal Castle in Kraków, is situated near the Niepołomice Forest.
As the former royal seat, it was visited by numerous Polish rulers and notable personages. Today the inside of the castle is the place where culture, art and history are visible.
In the museum, located within the Castle, one can visit the Gallery of 19th-century Polish art on loan from the collection of the National Museum in Kraków, the castle chapel with the paraments from the parish church in Niepołomice, founded by Casimir III the Great, as well as royal documents, rooms with game trophies and an office which belonged to Włodzimierz Puchalski (1909–1979), a Polish scientist and photographer. The collection includes cameras, personal memorabilia as well as over a hundred thousand photo frames and hundreds of nature shots from the Polish territory as well as the North Pole and the South Pole.
When walking along the castle cloister, visitors can also admire some examples of Renaissance architecture.
Elaborated by (The Museum of Niepołomice — the Niepołomice Royal Castle, © all rights reserved
Photograph by Krystyna Konopko (The Museum of Niepołomice — the Niepołomice Royal Castle), © all rights reserved

domain: travel


AdventHealth has 500 coronavirus testing kits for the Daytona International Speedway site.
At 8:30 a.m. Friday, 41-year-old Brian Campbell pulled his car into the already bustling line at Daytona International Speedway to be one of the first residents to get a drive-thru coronavirus test from AdventHealth.
Even though his appointment wasn’t until 9 a.m., and the site itself wouldn’t open until then, there were already 30 cars ahead of him.
"I guess I’m worried," said Campbell in a phone interview after his test. He developed a cough, fever and chest tightness on Wednesday. "Under normal circumstances I wouldn’t be concerned about the symptoms."
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Campbell was one of 452 residents with an appointment for the first drive-thru testing site in Volusia County as of 9 a.m., according to AdventHealth spokesman Jeff Grainger. Of those residents, 266 had appointments on Friday, the rest were spread throughout the weekend.
"We’re hopeful logistically to be able to do more than 500 tests in a day, but will have supplies for more," Grainger said in an email Thursday night, explaining that the tests come from a private vendor and not the state. "Our staff will be outfitted with the proper protective equipment recommended by the CDC. Those driving up to be tested are asked to stay in the cars the entire time."
[READ MORE: Volusia testing sites]
[READ MORE: Coronavirus drive-through testing site starts today Daytona International Speedway]
By 9 a.m., cars were lined up from the center of the Speedway’s front parking lot to NASCAR Drive. Over the next 15 minutes, the line dwindled as AdventHealth started the testing process, but a steady stream of cars continued to make their way in.
Campbell, who is unsure how he may have contracted the virus, waited in line for nearly an hour. He was stopped at two checkpoints: The first to ensure he had an appointment and symptoms of coronavirus; the second to give his name and confirm his appointment. By 9:33 a.m. he was on his way home.
"You pull up, they give you a cup with directions you spit into the cup, give it back to them and they put it in a bag," Campbell said. "It took less than five minutes."
Typically, coronavirus testing involves a swab to the cheek or nose; however, AdventHealth is using a different testing kit than the state, according to Grainger.
Around 30 staff members are working the tent, according to Grainger. But the hospital system is willing to adjust that based on the demand for testing.
"We’re asking people to pre-register on AdventHealthCoronaVirusTesting.com for their convenience so that all paperwork can be completed before they arrive and we can expedite the testing process," he said. "We’re also trying to minimize wait times by spreading the volume throughout the day. We don’t anticipate any problems, but are working with law enforcement and the Speedway’s security staff to ensure a safe experience for everyone."
Sixty-year-old Terri Wilson decided to head to the site early for her 10 a.m. appointment. When she arrived, she said the line was "quite backed up." She didn’t leave until 11:18 a.m.
"They handled it very well and were informative," Wilson said in a phone interview after his test. "I was a little surprised at the test, though, cause everything I’ve seen was the swabs in the nose or the mouth. This was a cup and you had to sit there and just keep hacking up whatever you could get up out of your throat and spit in this cup. Some people were having difficulty doing that."
Wilson — who is considered high-risk because she has type-1 diabetes, heart complications and other health issues — thinks she may have gotten the virus from a friend who traveled to Florida from New York three weeks ago. Her friend ended up in a New York hospital with COVID-19.
"I’ve been having a sore throat and coughing. No fever but typically for me when I’m sick fever runs low, not high," she said. "I also have a little shortness of breath and I’m a little bit confused and dizzy. Each day it’s gotten a bit worse."
Until the testing site at the Daytona International Speedway was announced Thursday, Wilson had thought about making the drive to one of the sites in Orlando or Jacksonville to obtain a test. Campbell had an appointment with his primary care physician to get tested on Monday, but he didn’t want to wait.
There is no cost for the coronavirus test at AdventHealth’s drive-thru site. Residents also do not need a doctor’s order to get the test. Results are expected 48 hours after being tested, according to AdventHealth’s press release on the site.
The testing site at the Daytona International Speedway will be open Monday through Friday from 9 a.m. to 4 p.m. and Saturday and Sunday from 9 a.m. to 1 p.m., or as long as testing supplies are available.


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General Information on Fragoskala
The postal code of Fragoskala is 30100 and its telephone access code is +3026410.
Approximately 69 people live in Fragoskala.
On our Fragoskala page you can see Fragoskala Photos, explore Fragoskala's Map and nearby Destinations, find Fragoskala Hotels and check Fragoskala's Weather by following the links below and to the left.
Current Weather in Fragoskala
The weather conditions recorded for Fragoskala on Thursday, November 26 at 10:23 am are:
Clear sky and the temperature is 7.6°.
The temperature today is expected to range between 2° and 15°.
The wind is blowing at a speed of 2 Bf (4.6 mph) from the North East (40.0°) and the pressure is 1022 hPa.
Today's sunrise was at 07:28 and the sunset is at 17:15.
Weather Forecast for Fragoskala
|Thu 26/11||6° - 15°||1 Bf NE|
|Fri 27/11||8° - 19°||0 Bf NE|
|Sat 28/11||8° - 16°||0 Bf S|
|Sun 29/11||10° - 16°||1 Bf SE|
|Mon 30/11||10° - 15°||1 Bf NE|
|Tue 01/12||7° - 14°||1 Bf NE|
|Wed 02/12||7° - 14°||0 Bf S|
Restaurants Near Fragoskala
Businesses Near Fragoskala
Map of Fragoskala


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window repair shop Horsington EN BA8 0
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Definitions of Window Repair
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It will be contingent on the state of the windows and what kind of replacements you’re considering, but restoration is frequently the less expensive option. This repair is essential as a way to protect against any leakage in your window. You therefore feel that you may credit repair yourself.
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Christmas parking present for Lancing shoppers
Shoppers in Lancing will receive an early Christmas present this festive season as Adur District Council waives charges at its car parks for all four Saturdays in December.
The aim of the move, which was introduced after discussions with traders, is to encourage people to shop local in the run up to Christmas and boost footfall on some of the busiest shopping days of the year.
Visitors will have an extra incentive to head to Lancing on December 21 when the Village Christmas Market will see dozens of traders set up in North Road for a family-friendly festive extravaganza.
Councillor Emma Evans, Adur District Council’s Executive Member for Environment, said: “With the festive period on the way, it's important that we do what we can to encourage people to buy local and shop in their nearby high streets.
“The idea of free parking has been championed by the Lancing Traders Association. While there will be a small financial outlay for the Council, I believe this early Christmas present will give people an incentive to see what the excellent independent shops in the village have to offer - and then come back time and time again in the future.”
Heidi Rush, of the Lancing Traders' Association, said: “I want to thank the Council for their generosity in waiving the car park fees on these extremely important shopping days and look forward to welcoming people into the village to support their local traders.”
The free parking will be in place on December 7, 14, 21 and 28 at North Farm Road, Littlecroft and South Street car parks.
Demand is likely to be high for the third of those four dates as it coincides with the Lancing Village Christmas Market, run by the award-winning Adur Markets team in partnership with Lancing Parish Council.
Dozens of local traders have already confirmed they will be at the event selling a range of local Sussex produce and homemade goods, which will take place from 9am and 1pm.
Anyone who wishes to run a stall at the event can email firstname.lastname@example.org or call 07738 848 393.


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Much has been made about Capcom’s “Fab Five” agreement with Nintendo, with most agreeing that it was a poor move on Capcom’s part. The languishing sales, delays (Resident Evil 4) and cancellations (Dead Phoenix) have done little to back up Capcom’s deal. One of those promising games did see the light of day and debuted with much fanfare and savior-like worshipping. That game’s name was Viewtiful Joe. Critics had you believe that it would be the second coming of the action/platforming genre (it was). It was to be one of the best games of last year (it was). And it would single-handedly destroy the menace known as Paris Hilton and her slutty grip on America (ummm?still working on it). But for all the god-like promises the press served up- and Capcom’s wishes for gamers worldwide to be “Henshin-A-Go-Going”- most GameCube owners failed to take notice (damn you, Mario Party 37!). It made such an impression that when the Blockbuster clerk read the box for the PS2 version, he wondered aloud, “Viewtiful Joe?never heard of it.” Somewhere, the ghost of gaming’s past was crying.
Somehow, Capcom managed to make a game SO hardcore, most gamers never heard of it! Oh, the agony! But ever the savvy business folk, Capcom was convinced that Viewtiful Joe could sell viewtifully (I know, I know?) in greener pastures. Weighing the option of the system with the highest sales versus the behemoth that Japan currently uses for a doorstop (and what a doorstop!), the choice was clear. So almost a year later, Viewtiful Joe is back on the PlayStation 2- for many, for the first time. Perhaps the glossy-eyed gamers will take notice of the stunning cel-shaded 3D graphics that leap off the screen like a comic book come to life. Or perhaps the loving nod to old-school game play- with finger-blistering action- would make an impression. Or maybe, just maybe, the hardcore challenge would keep players glued to their Dual Shocks longer than Catwoman was in theatres. If PS2 gamers can wrap their noggins around a spiky blue hedgehog, they can welcome a spandex-clad superhero bent on saving platform gaming, right?
The story of Viewtiful Joe is pretty basic. While at a movie with his main squeeze Sylvia, Joe is startled to find a giant robot reach out of the screen and kidnap his gal. Even more surprising, Joe is snatched from reality and pulled into the movie world he was just watching. Guided by his idol, Captain Blue, Joe taken on the movie baddies to get his boo back. Things get a little complicated as the game goes on, losing some of its focus. But something is slightly puzzling about the events that play out. Before being snatched from the jaws of real-life, Joe is repeatedly fending off the advances of his attractive lady to focus on the movie. Wanting to create a few theatrical moments of her own, Sylvia is reduced to begging for a little “hey-hey” with no luck. Not to say anything about Joe here, but there’s enough subtext here to make Ricky Martin lean forward with interest. But I digress.
There are no hidden implications regarding Viewtiful Joe’s graphics. This is one of the more visually-stunning games I have ever played. Using the cel-shading effect- 3D polygons given a cartoon-like appearance- Viewtiful manages to take the almost-clich? technique to the next level. Characters live and breathe within the comic-book world, bursting with life and color. Animation is fluid and mimics its 2D forefathers well, missing none of the stiffness that plagues many 3D games. The larger-than-life environments, while lacking variation, are beautifully rendered in blazing colors. And those visual effects! Hits, explosions (there are lots), and other pyrotechnics look great. The Slow effect, the Mach Speed rush- with speed-line blurring- and Zoom effect are nicely done. Another great touch is the retro-movie filter on the screen when you revert back to regular Joe. There is some slight slowdown in overpopulated spots, but nothing of concern. In a way, it’s another nod to its platforming roots.
Viewtiful Joe’s audio may not have received the same TLC as the visuals, but is great nonetheless. The soundtrack lacks memorable tunes, but each song rings with bouncy beats and energetic pacing. Sound effects are good and match the onscreen action. The stunner here is the voice acting, which manages to escape the dreaded Capcom hack job. The voice actors actually sound like their characters, and their enthusiasm is infectious (no wooden reading here, folks). Joe’s trademark “Henshin-A-Go-Go, Baby!” has a cheerful coolness to it, and several characters- such as the preacher-like gruffness of dinosaur Davidson (“Davidson is in the house!”)- have uniqueness commonly lacking in Capcom’s games.
The controls of VJ seem a little much for an action-platformer- at first. Being the fighting-game masters they are, Capcom opted for a pugilist-friendly combat scheme. The face buttons are devoted to punch, kick and Zoom functions (also controlled by the right analog stick), while the L1 and R1 triggers handle the visual effects (or “VFX”). The digital pad and left analog stick control movement. I prefer the digital pad for movement, as the left thumb stick feels slippery when controlling Joe, leading to unnecessary dodges. The Zoom button controls more precisely with the circle button rather than the analog stick. It all seems daunting at first as you’re trying to remember how to handle your powers. Once you spend some time with the controls, you’ll be Slow-mo Zoom punching in no time.
Flashy aesthetics aside, the meaty innards of Viewtiful Joe is unquestionably the game play. With yet another throwback to the “game play over graphics” days of old, VJ thrusts its play mechanics front and center for display. From the innovative use of time-tinkering (let’s try to forget Blinx, shall we?) to the fighting-inspired combat, game play in VJ draws attention beneath the surface. A lack of innovation ultimately reveals itself, but its back-to-basics approach is welcome compared to the stale attempts at cleverness in the past few years (Rareware, I’m looking at you).
The main attention grabber to VJ’s game play is the brawler-inspired combat system. Deviating far from the platforming norm of leaps and butt-slams, Joe’s chop-socky antics force you to become engaged in the fights. Kicks and punches are standard fare, and a string of attacks creates basic combos. Taking on your foe in hand-to-hand battles is encouraged, as dodging or ducking an attack leaves the opponent open for a few hits. When joined in tandem with the VFX powers- Slow, Mach speed and Zoom- this opens up a special delivery of pain on your enemies. Knowing how to manipulate your powers can rack up huge combos and points. For example, Zooming in while in Slow increases the power behind your attacks, and a Zoom kick creates a spinning attack. This imaginative fighting scheme strays from the boredom of mowing through mindless minions, and eggs you on to better your skills.
The VFX powers also play a large role in the various levels. Certain objectives in each stage are only met with clever uses of Joe’s special skills. The Slow effect manipulates moving platforms and certain environment objects for safe crossing, and also creates a combustion effect in particular instances. The Mach Speed effect, though better suited for battling enemies- also affects platforms and speeds up movement across dangerous terrain. The Zoom feature puts your special moves to good use, as ground stomps and whirlwind jumps can open up new paths.
The VFX powers are essential for standing a chance, but are limited. The VFX meter gives you a restricted amount of juice for all those fancy powers. If your meter taps out, you revert back to ambiguous Joe. Not that Joe is particularly weak; he can dodge, kick and punch enemies for some nice combos. But turning back in Viewtiful Joe gives him the upper hand.
You can add to your impressive attack arsenal and stamina by purchasing special moves and items with your “V-points” (they’re like money, but more viewtiful!). But you can only earn the big items by dishing out whopping combos and nabbing them “Viewtifuls”. It’s another reason to spend time working on your attacks.
It’s just too bad that there’s little variation in the actual stages or foes. Most of the levels are simple- though lush and vibrant- horizontal treks, with occasional 3D camera movement thrown in. Some stages are short in length, while others stretch on for a little too long. Little surprises such as a side-scrolling shooter stage (in Joe’s coyly named “Six Machine”) break up the monotony of street and sewer levels. And apart from the VFX powers influencing certain stages, there is little interaction with the environments. Similarly, enemies are few in diversity- with a majority being similar-looking robots and costumed oddities.
Another tear in the spandex is the potential abuse of Joe’s moves. Mixing up your attacks with the VFX powers is great for discovering new combos and garnering points, but savvy (or unimaginative) players can scoot by on using one specific attack. This need for instant gratification comes at the expense of learning and having fun with the expansive fighting system.
Listening to the cries of the weaker-skilled players, Capcom tweaked Viewtiful Joe’s challenge for the PS2 release. New to the game is the easy “Sweet” mode (hopefully not a reference to Dude, Where’s My Car?). The “Kids” and “Adult” (kinky!) modes remain, along with unlockable modes of increased difficulty. Even on the standard settings, VJ provides a formidable challenge. The swarms of enemies give Joe some troubles, but the bigger trial lies in blasting through the enemies quickly while taking little damage. The game grades you on your fighting skills, damage you take, and time taken to pass each section- ranging from Viewtiful (what else?) to Crappy and beyond. Half the fun- and madness- lies in perfecting your skills and memorizing each level segment to earn a “Viewtiful”. In a way, it is a warm and fuzzy reminder of summer days spent playing a game trying to beat that nagging level.
Despite the respectable challenge, Viewtiful Joe is a short game. Some may not mind the length (games like Mega Man and Castlevania weren’t marathon runners, either), but those weaned on newer games may feel slighted. Despite the relatively few levels, a nice assortment of unlockables awaits skilled gamers. Four hidden characters are available with the completion of the difficulty levels: Dante (from Devil May Cry), leading lady Sylvia, Joe’s idol and mentor Captain Blue, and Dante’s sword Alabastor. Playing with the hidden characters alters the story and overall experience a bit, lending to a sense of greater replay. Two additional challenge levels- V-Rated and Ultra V-Rated (wonder what the “v” stands for?) – promise even tougher trials for Joe and the gang. A music video rounds out the list.
Capcom’s change of heart on Viewtiful Joe’s exclusivity is a gain for gamers everywhere. Reinvigorating the comatose platforming genre with style and substance, VJ proves that a great game doesn’t have to be overly complex. The spectacular graphics are more than eye candy, adding character to a game already swelling with personality. The audio is above-average for a Capcom effort, and the solid controls provide a great foundation for the flexible and excellent game play. And a host of unlockables balance out the slightly brief play time. While worth the full price of admission, Viewtiful Joe is an unbeatable bargain at $30. No true gamer should be without this game. With any luck, introducing Joe to the mainstream PS2 audience will get him the attention he deserved the first time. Maybe now he can live up to all those promises the critics raved about a year ago- perhaps even making us forget about a certain skanky Hilton sister. A hero like Viewtiful Joe is more than up for the challenge.

domain: game


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Sichuan pepper is a spice from the Sichuan cuisine of China's southwestern Sichuan Province. It has a unique aroma and flavor that is neither hot like chili peppers nor pungent like black pepper. Instead, it has slight lemony overtones and creates a tingly numbness in the mouth due to hydroxy-α-sanshool.
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