Two non-amidated host defence peptides named Pin2[G] and FA1 were evaluated against three types of pathogenic bacteria; two isolated from diabetic foot ulcer patients, Staphylococcus aureus UPD13 and Pseudomonas aeruginosa UPD3, and another from a commercial collection, Salmonella enterica serovar Typhimurium (ATCC 14028). In vitro experiments showed that the antimicrobial performance of the synthetic peptides, Pin2[G] and FA1, was modest, although FA1 was more effective than Pin2[G]. In contrast Pin2[G] had superior in vivo anti-infective activity to FA1 in rabbit wound infections by the diabetic foot ulcer pathogens S. aureus UPD13 and P. aeruginosa UPD3. Indeed, Pin2[G] reduced bacterial colony counts of both S. aureus UPD13 and P. aeruginosa UPD3 by >100,000-fold after 48-72 h on skin wounds of infected rabbits, while in similar infected wounds, FA1 had no major effects at 72-96 h of treatment. Ceftriaxone was equally effective vs. Pseudomonas but less effective vs. S. aureus infections. Additionally, the two peptides were evaluated in mice against intragastrically inoculated S. enterica ser. Typhimurium (ATCC 14028). Only Pin2[G], at 0.56 mg/kg, was effective in reducing systemic (liver) infection by >67-fold, equivalent to the effect of treatment with levofloxacin. Pin2[G] showed superior immunomodulatory activity in increasing chemokine production by a human bronchial cell line and suppressing poly(IC)-induced pro-inflammatory IL6 production. These data showed that the in vitro antimicrobial activity of these peptides was not correlated with their in vivo anti-infective activity, and suggest that other factors such as immunomodulatory activity were more important.

Florfenicol belongs to a class of phenicol antimicrobials widely used as feed additives and for the treatment of respiratory infections. In recent years, increasing resistance to florfenicol has been reported in Campylobacter spp., the leading foodborne enteric pathogen causing diarrheal diseases worldwide. Here, we reported the identification of fexA, a novel mobile florfenicol resistance gene in Campylobacter. Of the 100 Campylobacter jejuni strains isolated from poultry in Zhejiang, China, nine of them were shown to be fexA positive, and their whole genome sequences were further determined by integration of Illumina short-read and MinION long-read sequencing. The fexA gene was found in the plasmid of one strain and chromosomes of eight strains, and its location was verified by S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern blotting. Based on comparative analysis, the fexA gene was located within a region with the tet(L)-fexA-catA-tet(O) gene arrangement, demonstrated to be successfully transferrable among C. jejuni strains. Functional cloning indicated that acquisition of the single fexA gene significantly increased resistance to florfenicol, whereas its inactivation resulted in increased susceptibility to florfenicol in Campylobacter. Taken together, these results indicated that the emerging fexA resistance is horizontally transferable, which might greatly facilitate the adaptation of Campylobacter in food producing environments where florfenicols are frequently used.

Peroxidases are a group of heterogeneous family of enzyme that plays diverse biological functions. Ascorbate peroxidase is a redox enzyme that is reduced by trypanothione, which plays a central role in the redox defence system of Leishmania. In view of developing new and novel therapeutics, we have performed in silico studies in order to search for ligand library and identification of new drug candidates and its physiological role against promastigotes and intracellular amastigotes of Leishmania donovani. Our results demonstrated that the selected inhibitor ZINC96021026 has significant anti-leishmanial effect and effectively killed both free and intracellular forms of the parasite. ZINC96021026 was found to be identical to ML-240, a selective inhibitor of Valosin-containing protein (VCP) or p97, a member of AAA-ATPase protein family which was derived from the scaffold of DBeQ, targeting the D2-ATPase domain of the enzyme. ZINC96021026 (ML-240) thus have broad range of cellular functions, thought to be derived from its ability to unfold proteins or disassemble protein complexes besides inhibiting the ascorbate peroxidase activity. ML-240 may inhibits the parasite's ascorbate peroxidase leading to extensive apoptosis and inducing generation of reactive oxygen species. Taken together, our results demonstrated that ML-240 could be an attractive therapeutic option for treatment against leishmaniasis.

CYP450 enzymes are involved in biotransformation of chloroquine (CQ), but the role of the different metabolism profiles of this drug has not been properly investigated in relation to P. vivax recurrences. To investigate the influence of CYPs genotypes associated with CQ-metabolism on early recurrence rates of P. vivax, a case-control study was carried out. Cases included patients presenting an early recurrence (CQ-recurrent), defined as recurrence during the first 28 days after initial infection, plasma concentrations of CQ plus desethylchloroquine (DCQ, the major CQ metabolite) higher than 100 ng/mL. A control (CQ-responsive) with no parasite recurrence over the follow-up was also included. CQ and DCQ plasma levels were measured on Day 28. CQ CYPs (CYP2C8, CYP3A4 and CYP3A5) genotypes were determined by real-time PCR. An ex vivo study was conducted to verify CQ and DCQ efficacy in P. vivax isolates. The frequency of alleles associated with normal and slow metabolism was similar between the cases and controls for CYP2C8 (OR=1.45, 95% CI=0.51-4.14, p=0.570), CYP3A4 (OR=2.38, 95% CI=0.92-6.19, p=0.105) and CYP3A5 (OR=4.17, 95% CI=0.79-22.04, p=1.038) genes. DCQ levels were higher than CQ, regardless of the genotype. Regarding the DCQ/CQ rate, there was no difference between groups or between those patients who had a normal or mutant genotype. DCQ and CQ showed similar efficacy ex vivo. CYPs genotypes had no influence on early recurrence rates. Similar efficacy of CQ and DCQ ex vivo could explain the absence of therapeutic failure, despite presence of alleles associated with slow metabolism.

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Robert Guthrie
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Lima, Peru, Apr 23, 2020 / 10:02 am (CNA).- As the ongoing coronavirus lockdown in Peru leaves the working poor in a vulnerable situation, one priest has been working to ensure that thousands in need have access to food.

Fr. Omar Sánchez Portillo is the secretary general of Caritas Lurín, on metro Lima’s south side.

Sánchez has distributed more than 15,000 food baskets, with the help of donors and volunteers at the Beatitudes Association, which he founded, since the nationwide quarantine was declared March 15. Peru’s Ministry of Health has confirmed 19,000 cases of coronavirus with 530 deaths.

Recently, Sánchez also received a donation of 5,000 live chickens from a poultry farm. He found himself needing to quickly process the chickens for distribution.

Sánchez turned to his fellow priests in the diocese of Lurín with an appeal on Whatsapp. To his surprise, almost 30 priests showed up to volunteer, including Bishop-elect Cristobal Mejía, who was recently named bishop of Chulucanas.

The priests and other volunteers worked all day, plucking, cleaning and preparing the birds for distribution.

“Today has been a long day,” Sánchez commented on his Facebook page. “Thank you dear priests! Thank you for your example, your work, and your joy. I feel proud to belong to a such an active, alive diocese so full of God, and to be part of a presbyterate full of holiness and enthusiasm for our priestly mission.”

In a statement to ACI Prensa, CNA’s Spanish language news partner, Sánchez noted that in the Diocese of Lurín, which is comprised of 55 parishes, there are many poor people who do not have access to electricity or running water.

The priest estimates about 60% of the people in the diocese live in extreme poverty. Southern Lima, where his diocese is located, contains the third and fourth most COVID-infected areas in the country.

Sánchez also pointed out that most Peruvians lack the ability to save money, which leaves vulnerable populations even more at risk during the quarantine.

“A lot of people are out of work and out on the street, a lot of them are temporary workers, many of them earn a living day-to-day,” he said.

So far, volunteers have distributed 75,000 food baskets throughout the South Lima area. However, the needs remain great.

“Every day in the parishes there are people out looking, knocking on doors, that haven’t gotten any food, or what they have gotten isn’t enough and has already run out,” he explained.

 

Bridget O’Donnell, assistant director of student engagement at Penn State Brandywine, has been recognized as Advisor of the Year by the Association for the Promotion of Campus Activities.

Four Penn State World Campus energy and sustainability policy majors spent the year working with Pennsylvania boroughs to inventory greenhouse gas emissions, and coming up with climate action plans for reducing them.

House Democrats are demanding that companies return federal dollars that they say were intended for smaller businesses

Rebecca Mattson, head of faculty and research services for the H. Laddie Montague Jr. Law Library, Penn State University Libraries, and professor of legal research at Penn State Law at University Park, has been elected vice chair/chair elect of the Research Instruction and Patron Services Special Interest Section of the American Association of Law Libraries.

Selected poems of Rachelle Bowser, Rachel Mennies, Erin Murphy and Eleanor Stanford have been chosen to represent the Pennsylvania Center for the Book’s 2020 Public Poetry Project, with poetry interpreted into art posters for the annual event.

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"This is the moment of truth," says the Spain midfielder ahead of his second U21 EURO final against Germany.

Türkiye devleti ile uluslararası alanda terör örgütü olarak kabul edilen PKK arasındaki çözüm sürecinin çökmesi, Temmuz 2015’te çatışmaların yeniden başlaması ve daha sonra derinleşen şiddet sarmalı, yeni bir çözüm sürecinin inşasını hiç olmadığı kadar gerekli kılıyor.

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Saskia perseveres through language learning and connects with a young Albanian girl who becomes a follower of Jesus.

Concern for their students and adapting to remote teaching are only a few of the stressors that teachers are facing during the coronavirus pandemic. In response, the Pennsylvania State Education Association (PSEA) has partnered with Sebrina Doyle, a graduate fellow in the College of Education, to offer mindfulness-based stress reduction training via Zoom to their members – to help alleviate feelings of helplessness, fear and anxiety. Doyle offered the hour-long webinar two days this month to approximately 700 PSEA members.

Saskia perseveres through language learning and connects with a young Albanian girl who becomes a follower of Jesus.

From the 2nd July 2020, the Danish airline DAT will fly directly from Berlin-Tegel to Rønne (Bornholm). The popular Baltic island can then be reached within an hour’s flight time on Thursdays and Sundays until the 9th August.

The lawsuit, filed in 2014, alleges that the state was severely underfunding schools, forcing school districts to lean heavily on property taxes, which especially disadvantages students in property-poor areas.

The Rural School and Community Trust and the AASA, the School Superintendents Association, say the partnership will allow the two groups to expand their reach and play off each other's strengths.

Saskia perseveres through language learning and connects with a young Albanian girl who becomes a follower of Jesus.

By Cardinal Gerhard Müller

“Let not your heart be troubled!” (John 14:1)

In the face of growing confusion about the doctrine of the Faith, many bishops, priests, religious and lay people of the Catholic Church have requested that I make a public testimony about the truth of revelation. It is the shepherds' very own task to guide those entrusted to them on the path of salvation. This can only succeed if they know this way and follow it themselves. The words of the Apostle here apply: “For above all I have delivered unto you what I have received” (1 Cor. 15:3). Today, many Christians are no longer even aware of the basic teachings of the Faith, so there is a growing danger of missing the path to eternal life. However, it remains the very purpose of the Church to lead humanity to Jesus Christ, the light of the nations (see LG 1). In this situation, the question of orientation arises. According to John Paul II, the Catechism of the Catholic Church is a “safe standard for the doctrine of the faith” (Fidei Depositum IV). It was written with the aim of strengthening the Faith of the brothers and sisters whose belief has been massively questioned by the “dictatorship of relativism.”

1. The one and triune God revealed in Jesus Christ

The epitome of the Faith of all Christians is found in the confession of the Most Holy Trinity. We have become disciples of Jesus, children and friends of God by being baptized in the name of the Father and of the Son and of the Holy Spirit. The distinction of the three persons in the divine unity (CCC 254) marks a fundamental difference in the belief in God and the image of man from that of other religions. Religions disagree precisely over this belief in Jesus the Christ. He is true God and true Man, conceived by the Holy Spirit and born of the Virgin Mary. The Word made flesh, the Son of God, is the only Savior of the world (CCC 679) and the only Mediator between God and men (CCC 846). Therefore, the first letter of John refers to one who denies His divinity as an antichrist (1 John 2:22), since Jesus Christ, the Son of God, is from eternity one in being with God, His Father (CCC 663). We are to resist the relapse into ancient heresies with clear resolve, which saw in Jesus Christ only a good person, brother and friend, prophet and moralist. He is first and foremost the Word that was with God and is God, the Son of the Father, Who assumed our human nature to redeem us and Who will come to judge the living and the dead. Him alone, we worship in unity with the Father and the Holy Spirit as the Only and True God (CCC 691).

2. The Church

Jesus Christ founded the Church as a visible sign and instrument of salvation realized in the Catholic Church (816). He gave His Church, which “emerged from the side of the Christ who died on the Cross” (766), a sacramental constitution that will remain until the Kingdom is fully achieved (CCC 765). Christ, the Head, and the faithful as members of the body, are a mystical person (CCC 795), which is why the Church is sacred, for the one Mediator has designed and sustained its visible structure (CCC 771). Through it the redemptive work of Christ becomes present in time and space via the celebration of the Holy Sacraments, especially in the Eucharistic Sacrifice, the Holy Mass (CCC 1330). The Church conveys with the authority of Christ the divine revelation, which extends to all the elements of doctrine, “including the moral teaching, without which the saving truths of the faith cannot be preserved, explained, and observed” (CCC 2035).

3. Sacramental Order

The Church is the universal sacrament of salvation in Jesus Christ (CCC 776). She does not reflect herself, but the light of Christ, which shines on her face. But this happens only when the truth revealed in Jesus Christ becomes the point of reference, rather than the views of a majority or the spirit of the times; for Christ Himself has entrusted the fullness of grace and truth to the Catholic Church (CCC 819), and He Himself is present in the sacraments of the Church.

The Church is not a man-made association whose structure its members voted into being at their will. It is of divine origin. "Christ himself is the author of ministry in the Church. He set her up, gave her authority and mission, orientation and goal (CCC 874). The admonition of the Apostle is still valid today, that cursed is anyone who proclaims another gospel, “even if we ourselves were to give it or an angel from heaven” (Gal 1:8). The mediation of faith is inextricably bound up with the human credibility of its messengers, who in some cases have abandoned the people entrusted to them, unsettling them and severely damaging their faith. Here the Word of Scripture describes those who do not listen to the truth and who follow their own wishes, who flatter their ears because they cannot endure sound doctrine (cf. 2 Tim 4:3-4).

The task of the Magisterium of the Church is to “preserve God’s people from deviations and defections” in order to “guarantee them the objective possibility of professing the true faith without error” (890). This is especially true with regard to all seven sacraments. The Holy Eucharist is “source and summit of the Christian life” (CCC 1324). The Eucharistic Sacrifice, in which Christ includes us in His Sacrifice of the Cross, is aimed at the most intimate union with Him (CCC 1382). Therefore, the Holy Scripture admonishes with regard to the reception of the Holy Communion: “Whoever eats unworthily of the bread and drinks from the Lord's cup makes himself guilty of profaning the body and of the blood of the Lord” (1 Cor 11:27). “Anyone conscious of a grave sin must receive the sacrament of Reconciliation before coming to communion” (CCC 1385). From the internal logic of the sacrament, it is understood that divorced and civilly remarried persons, whose sacramental marriage exists before God, as well as those Christians who are not in full communion with the Catholic Faith and the Church, just as all those who are not disposed to receive the Holy Eucharist fruitfully (CCC 1457), because it does not bring them to salvation. To point this out corresponds to the spiritual works of mercy.

The confession of sins in Holy Confession at least once a year is one of the Church’s commandments (CCC 2042). When the believers no longer confess their sins and no longer experience the absolution of their sins, salvation becomes impossible; after all, Jesus Christ became Man to redeem us from our sins. The power of forgiveness that the Risen Lord has given to the Apostles and their successors in the ministry of bishops and priests applies also for mortal and venial sins which we commit after Baptism. The current popular practice of confession makes it clear that the conscience of the faithful is not sufficiently formed. God's mercy is given to us, that we might fulfil His Commandments to become one with His Holy Will, and not so as to avoid the call to repentance (CCC 1458).

“The priest continues the work of redemption on earth” (CCC 1589). The ordination of the priest “gives him a sacred power” (CCC 1592), which is irreplaceable, because through it Jesus becomes sacramentally present in His saving action. Therefore, priests voluntarily opt for celibacy as "a sign of new life" (CCC 1579). It is about the self-giving in the service of Christ and His coming kingdom.

4. Moral Law

Faith and life are inseparable, for Faith apart from works is dead (CCC 1815). The moral law is the work of divine wisdom and leads man to the promised blessedness (CCC 1950). Consequently, the "knowledge of the divine and natural law is necessary" to do good and reach this goal (CCC 1955). Accepting this truth is essential for all people of good will. For he who dies in mortal sin without repentance will be forever separated from God (CCC 1033). This leads to practical consequences in the lives of Christians, which are often ignored today (cf 2270-2283; 2350-2381). The moral law is not a burden, but part of that liberating truth (cf Jn 8:32) through which the Christian walks on the path of salvation and which may not be relativized.

5. Eternal Life

Many wonder today what purpose the Church still has in its existence, when even bishops prefer to be politicians rather than to proclaim the Gospel as teachers of the Faith. The role of the Church must not be watered down by trivialities, but its proper place must be addressed. Every human being has an immortal soul, which in death is separated from the body, hoping for the resurrection of the dead (CCC 366). Death makes man's decision for or against God definite. Everyone has to face the particular judgement immediately after death (CCC 1021). Either a purification is necessary, or man goes directly into heavenly bliss and is allowed to see God face to face. There is also the dreadful possibility that a person will remain opposed to God to the very end, and by definitely refusing His Love, "condemns himself immediately and forever" (CCC 1022). “God created us without us, but He did not want to save us without us” (CCC 1847). The eternity of the punishment of hell is a terrible reality, which - according to the testimony of Holy Scripture - attracts all who “die in the state of mortal sin” (CCC 1035). The Christian goes through the narrow gate, for “the gate is wide, and the way that leads to ruin is wide, and many are upon it” (Mt 7:13).

To keep silent about these and the other truths of the Faith and to teach people accordingly is the greatest deception against which the Catechism vigorously warns. It represents the last trial of the Church and leads man to a religious delusion, “the price of their apostasy” (CCC 675); it is the fraud of Antichrist. “He will deceive those who are lost by all means of injustice; for they have closed themselves to the love of the truth by which they should be saved” (2 Thess 2:10).

Call

As workers in the vineyard of the Lord, we all have a responsibility to recall these fundamental truths by clinging to what we ourselves have received. We want to give courage to go the way of Jesus Christ with determination, in order to obtain eternal life by following His commandments (CCC 2075).

Let us ask the Lord to let us know how great the gift of the Catholic Faith is, through which opens the door to eternal life. “For he that shall be ashamed of me, and of my words, in this adulterous and sinful generation: The Son of Man also will be ashamed of him, when He shall come in the glory of his Father with the holy angels.” (Mark 8:38). Therefore, we are committed to strengthening the Faith by confessing the truth which is Jesus Christ Himself.

We too, and especially we bishops and priests, are addressed when Paul, the Apostle of Jesus Christ, gives this admonition to his companion and successor, Timothy: “I charge thee, before God and Jesus Christ, Who shall judge the living and the dead, by His coming, and His kingdom: Preach the word: be instant in season, out of season: reprove, entreat, rebuke in all patience and doctrine. For there shall be a time, when they will not endure sound doctrine; but, according to their own desires, they will heap to themselves teachers, having itching ears: And will indeed turn away their hearing from the truth, but will be turned unto fables. But be thou vigilant, labour in all things, do the work of an evangelist, fulfil thy ministry. Be sober.” (2 Tim 4:1-5).

May Mary, the Mother of God, implore for us the grace to remain faithful without wavering to the confession of the truth about Jesus Christ.

United in faith and prayer,

Gerhard Cardinal Müller, Prefect of the Congregation for the Doctrine of the Faith 2012-2017

 

Editor's note: After this text was published, the cardinal's office submitted to CNA three amendments to the text originally submitted to CNA. Two were minor syntactical corrections. The third change replaced the word "to" with "cannot" in the following phrase: "just as all who are not properly disposed, to cannot receive the Holy Eucharist fruitfully (CCC 1457) because it does not bring them to salvation."

 

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