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Pope Francis ends his visit to Cuba on Tuesday with a Mass at the country's most revered shrine and a pep talk with families before flying north to Washington for the start of his U.S. tour.

Francis' address to families and symbolically potent flight to the United States underscore two of the big themes of his Cuba pilgrimage — encouraging reconciliation within families and between the U.S. and Cuba. He worked behind the scenes as mediator in 18 months of secret talks on re-establishing diplomatic relations between the two nations.

On his arrival in Cuba, the pope described the success of the negotiations as an example of peacemaking for the entire world. The Vatican spokesman said Monday night that this trip was aimed partly at encouraging progress in the continuing effort to normalize U.S.-Cuba ties in fields ranging from commerce to environmental cooperation.

Beyond its importance to the pope, the state of the family has been a longtime concern for the Roman Catholic Church in Cuba. Economic deprivation and successive waves of emigration have left many families broken and divided, and the church has focused intensely in recent years on trying to encourage traditional values like hard work, respect and fidelity that many Cubans worry have been lost over the years.

Those concerns about moral degradation are widespread among Cubans regardless of how religious they are.

While around 10 percent regularly attend Mass, many more believe in religious icons like the Virgin of Charity of Cobre, whose sanctuary is important to both observant Catholics and followers of Afro-Cuban Santeria traditions. The foot-tall wooden statue is kept in an ivory-colored church with soaring red domes nestled in the shadow of the Sierra Maestra mountains in the small community of Cobre just outside Santiago. One corner of the church where Francis will celebrate Mass is dedicated to offerings left for the Virgin, including votives and thousands of handwritten notes.

"She means so much," said Juana Isabel Gonzalez Huart, a retired state worker. "She's the mother who protects us."

Before flying to Santiago on Monday, Francis celebrated Mass in Holguin, a city of about 300,000 in eastern Cuba. In his homily, he pressed some of the subtle themes he has developed during this balancing act of a Cuban visit. He told the crowd of how Jesus picked a lowly and despised tax collector, Matthew, and instructed him without casting judgment to follow him. That act of mercy changed Matthew forever.

Francis told the Cubans that they, too, should allow themselves "to slowly overcome our preconceptions and our reluctance to think that others, much less ourselves, can change."

"Do you believe it is possible that a tax collector can be a servant?" he asked on Day 3 of his visit to the island. "Do you believe it is possible that a traitor can become a friend?"

It was a theme Francis sketched out Sunday night in an off-the-cuff encounter with young people. He encouraged them to dream big about what their life could be like, and not be "boxed in" by ideologies or preconceptions about others.

"If you are different than me, why don't we talk?" Francis asked the crowd. "Why do we always throw rocks at that which separates us?"

The message comes at a delicate moment of change in Cuba. Beside the re-establishment of diplomatic relations, the communist government is undertaking modest free-market reforms that have opened some sectors of the economy to private enterprise, creating socioeconomic inequality and growing cynicism, particularly among young people.

As a result, Francis has emphasized themes of reconciliation and looking beyond prejudice and ideologies.

After arriving in Santiago, the pope went to the Sanctuary of the Virgin of Charity of Cobre, the site of the Mass on Tuesday. After laying a bouquet at the feet of the statue, Francis made the sign of the cross and prayed, sitting and silent, for about 10 minutes. He then stood and recited a prayer.

Francis appeared to be in some discomfort walking. He has needed extra help getting up and down stairs during this trip, and the Vatican spokesman acknowledged Monday that the pontiff wasn't moving around well. Francis suffers from sciatica and has a bad knee.

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Associated Press writers E. Eduardo Castillo, Michael Weissenstein and Anne-Marie Garcia in Havana and Andrea Rodriguez in Holguin, Cuba, contributed to this report.

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Nicole Winfield on Twitter: https://twitter.com/nwinfield

Michael Weissenstein on Twitter: https://twitter.com/mweissenstein