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Article ; Online: Unmasking the Mechanism behind Miltefosine: Revealing the Disruption of Intracellular Ca

Benaim, Gustavo / Paniz-Mondolfi, Alberto

2024 Volume 14, Issue 4

Abstract: Originally developed as a chemotherapeutic agent, miltefosine (hexadecylphosphocholine) is an inhibitor of phosphatidylcholine synthesis with proven antiparasitic effects. It is the only oral drug approved for the treatment of Leishmaniasis and American ... ...

Abstract	Originally developed as a chemotherapeutic agent, miltefosine (hexadecylphosphocholine) is an inhibitor of phosphatidylcholine synthesis with proven antiparasitic effects. It is the only oral drug approved for the treatment of Leishmaniasis and American Trypanosomiasis (Chagas disease). Although its precise mechanisms are not yet fully understood, miltefosine exhibits broad-spectrum anti-parasitic effects primarily by disrupting the intracellular Ca
MeSH term(s)	Humans ; Phosphorylcholine/analogs & derivatives ; Phosphorylcholine/pharmacology ; Phosphorylcholine/therapeutic use ; Chagas Disease/drug therapy ; Chagas Disease/parasitology ; Chagas Disease/metabolism ; Calcium/metabolism ; Leishmaniasis/drug therapy ; Leishmaniasis/metabolism ; Leishmaniasis/parasitology ; Homeostasis/drug effects ; Animals ; Antiprotozoal Agents/pharmacology ; Antiprotozoal Agents/therapeutic use ; Mitochondria/metabolism ; Mitochondria/drug effects ; Leishmania/drug effects ; Leishmania/metabolism ; Trypanosoma cruzi/drug effects ; Trypanosoma cruzi/metabolism
Chemical Substances	miltefosine (53EY29W7EC) ; Phosphorylcholine (107-73-3) ; Calcium (SY7Q814VUP) ; Antiprotozoal Agents
Language	English
Publishing date	2024-03-27
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom14040406
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Article ; Online: Editorial: Chagas disease novel drug targets and treatments.

Duschak, Vilma G / Paniz Mondolfi, Alberto E / Benaim, Gustavo

Frontiers in cellular and infection microbiology

2023 Volume 13, Page(s) 1199715

Language	English
Publishing date	2023-05-26
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2023.1199715
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Article ; Online: Reappraisal of p16 for Determining HPV Status of Head and Neck Carcinomas Arising in HPV Hotspots.

Bhardwaj, Swati / Gitman, Melissa / Ramirez, Juan D / Paniz-Mondolfi, Alberto / Westra, William H

The American journal of surgical pathology

2024 Volume 48, Issue 5, Page(s) 581–587

Abstract: In an era of head and neck oncology where HPV status will soon dictate patient management, reliable HPV detection is critical. P16 immunohistochemistry (IHC) is currently recommended as the test of choice for oropharyngeal squamous cell carcinomas ( ... ...

Abstract	In an era of head and neck oncology where HPV status will soon dictate patient management, reliable HPV detection is critical. P16 immunohistochemistry (IHC) is currently recommended as the test of choice for oropharyngeal squamous cell carcinomas (OPSCCs). The purpose of this study was to determine the performance characteristics of p16 IHC based on a large clinical experience of squamous cell carcinomas (SCC) arising from HPV hot-spot regions of the head and neck. Consecutive OPSCCs, sinonasal SCCs, and metastatic SCCs of unknown primary sites were evaluated for the presence of HPV by p16 IHC and PCR-based HPV DNA testing as part of clinical care. For discrepant cases, high-risk HPV E6/E7 mRNA in situ hybridization (ISH) and, when possible, matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (MassArray) genotyping were performed. 746 cancers underwent HPV testing by p16 IHC and DNA PCR genotyping. There was a 95.6% concordance between the 2 assays. Of the 33 discrepant cases, 32 cases (4.3%) were p16 positive but HPV DNA negative. In these cases, 68% were positive for mRNA ISH, invariably related to a non-16 HPV genotype. P16 IHC had an overall accuracy of 98.8%, a sensitivity of 99.8%, and a specificity of 92.1%. P16 IHC is a sensitive and specific assay for determining HPV status. HPV DNA PCR appears vulnerable to HPV genotype diversity and is prone to missing rare non-16 genotypes. HPV mRNA ISH is a practical and reliable direct measure of HPV that may help eliminate the small number of false-positive p16 cases and avoid potential patient harm related to erroneous HPV classification.
MeSH term(s)	Humans ; Papillomavirus Infections/complications ; Papillomavirus Infections/diagnosis ; Papillomavirus Infections/pathology ; Head and Neck Neoplasms ; Squamous Cell Carcinoma of Head and Neck ; Carcinoma, Squamous Cell/pathology ; DNA, Viral/genetics ; RNA, Messenger ; Papillomaviridae/genetics ; Cyclin-Dependent Kinase Inhibitor p16/analysis ; Oropharyngeal Neoplasms
Chemical Substances	DNA, Viral ; RNA, Messenger ; Cyclin-Dependent Kinase Inhibitor p16
Language	English
Publishing date	2024-03-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	752964-8
ISSN	1532-0979 ; 0147-5185
ISSN (online)	1532-0979
ISSN	0147-5185
DOI	10.1097/PAS.0000000000002204
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Article ; Online: Detangling the Crosstalk Between

Castañeda, Sergio / Paniz-Mondolfi, Alberto / Ramírez, Juan David

Frontiers in cellular and infection microbiology

2022 Volume 12, Page(s) 852900

Abstract: Helminth infections remain a global public health issue, particularly in low- and middle-income countries, where roundworms from ... ...

Abstract	Helminth infections remain a global public health issue, particularly in low- and middle-income countries, where roundworms from the
MeSH term(s)	Animals ; Ascaris ; Gastrointestinal Microbiome ; Helminthiasis/parasitology ; Helminths/physiology ; Swine ; Trichuris
Language	English
Publishing date	2022-05-25
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2022.852900
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Article ; Online: Berenice's Legacy, Ending Silence, and Serving Justice: A Call for Comprehensive Chagas Testing in the US Pediatric Population.

Mallikarjuna, Priya / DeFelice, Nicholas / Ward, Matthew J / Suarez, Jose A / Ramirez, Juan David / Paniz-Mondolfi, Alberto

Journal of the Pediatric Infectious Diseases Society

2024 Volume 13, Issue 4, Page(s) 263

MeSH term(s)	Humans ; Chagas Disease/diagnosis ; United States ; Child ; Mass Screening
Language	English
Publishing date	2024-03-02
Publishing country	England
Document type	Journal Article ; Historical Article
ZDB-ID	2668791-4
ISSN	2048-7207 ; 2048-7193
ISSN (online)	2048-7207
ISSN	2048-7193
DOI	10.1093/jpids/piae019
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Article ; Online: The Rationale for Use of Amiodarone and its Derivatives for the Treatment of Chagas' Disease and Leishmaniasis.

Benaim, Gustavo / Paniz-Mondolfi, Alberto E / Sordillo, Emilia Mia

Current pharmaceutical design

2020 Volume 27, Issue 15, Page(s) 1825–1833

Abstract: The repurposing or repositioning of previously-approved drugs has become an accepted strategy for the expansion of the pharmacopeia for neglected diseases. Accordingly, amiodarone, an inexpensive and extensively- used class III antiarrhythmic has been ... ...

Abstract	The repurposing or repositioning of previously-approved drugs has become an accepted strategy for the expansion of the pharmacopeia for neglected diseases. Accordingly, amiodarone, an inexpensive and extensively- used class III antiarrhythmic has been proposed as a treatment for Chagas' disease and leishmaniasis. Amiodarone has a potent trypanocidal and leishmanicidal action, mainly acting through the disruption of parasite intracellular Ca
MeSH term(s)	Amiodarone/pharmacology ; Amiodarone/therapeutic use ; Animals ; Calcium ; Chagas Disease/drug therapy ; Dogs ; Leishmaniasis/drug therapy ; Trypanocidal Agents ; Trypanosoma cruzi
Chemical Substances	Trypanocidal Agents ; Amiodarone (N3RQ532IUT) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2020-09-08
Publishing country	United Arab Emirates
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1304236-1
ISSN	1873-4286 ; 1381-6128
ISSN (online)	1873-4286
ISSN	1381-6128
DOI	10.2174/1381612826666200928161403
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Article ; Online: Validation of Oxford nanopore sequencing for improved New World Leishmania species identification via analysis of 70-kDA heat shock protein.

Patiño, Luz Helena / Ballesteros, Nathalia / Muñoz, Marina / Jaimes, Jesús / Castillo-Castañeda, Adriana C / Madigan, Roy / Paniz-Mondolfi, Alberto / Ramírez, Juan David

Parasites & vectors

2023 Volume 16, Issue 1, Page(s) 458

Abstract: Background: Leishmaniasis is a parasitic disease caused by obligate intracellular protozoa of the genus Leishmania. This infection is characterized by a wide range of clinical manifestations, with symptoms greatly dependent on the causal parasitic ... ...

Abstract	Background: Leishmaniasis is a parasitic disease caused by obligate intracellular protozoa of the genus Leishmania. This infection is characterized by a wide range of clinical manifestations, with symptoms greatly dependent on the causal parasitic species. Here we present the design and application of a new 70-kDa heat shock protein gene (hsp70)-based marker of 771 bp (HSP70-Long). We evaluated its sensitivity, specificity and diagnostic performance employing an amplicon-based MinION™ DNA sequencing assay to identify different Leishmania species in clinical samples from humans and reservoirs with cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL). We also conducted a comparative analysis between our novel marker and a previously published HSP70 marker known as HSP70-Short, which spans 330 bp. Methods: A dataset of 27 samples from Colombia, Venezuela and the USA was assembled, of which 26 samples were collected from humans, dogs and cats affected by CL and one sample was collected from a dog with VL in the USA (but originally from Greece). DNA was extracted from each sample and underwent conventional PCR amplification utilizing two distinct HSP70 markers: HSP70-Short and HSP70-Long. The subsequent products were then sequenced using the MinION™ sequencing platform. Results: The results highlight the distinct characteristics of the newly devised HSP70-Long primer, showcasing the notable specificity of this primer, although its sensitivity is lower than that of the HSP70-Short marker. Notably, both markers demonstrated strong discriminatory capabilities, not only in distinguishing between different species within the Leishmania genus but also in identifying instances of coinfection. Conclusions: This study underscores the outstanding specificity and effectiveness of HSP70-based MinION™ sequencing, in successfully discriminating between diverse Leishmania species and identifying coinfection events within samples sourced from leishmaniasis cases.
MeSH term(s)	Humans ; Animals ; Dogs ; Cats ; Nanopore Sequencing ; Cat Diseases ; Coinfection ; Dog Diseases/diagnosis ; Dog Diseases/parasitology ; Leishmania/genetics ; Leishmaniasis, Cutaneous/diagnosis ; Leishmaniasis, Cutaneous/parasitology ; Leishmaniasis, Visceral/veterinary ; HSP70 Heat-Shock Proteins/genetics
Chemical Substances	HSP70 Heat-Shock Proteins
Language	English
Publishing date	2023-12-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2409480-8
ISSN	1756-3305 ; 1756-3305
ISSN (online)	1756-3305
ISSN	1756-3305
DOI	10.1186/s13071-023-06073-9
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Article ; Online: Mayaro virus detection by integrating sample preparation with isothermal amplification in portable devices.

Alipanah, Morteza / Manzanas, Carlos / Hai, Xin / Lednicky, John A / Paniz-Mondolfi, Alberto / Morris, J Glenn / Fan, Z Hugh

Analytical and bioanalytical chemistry

2023 Volume 415, Issue 23, Page(s) 5605–5617

Abstract: Mayaro virus (MAYV) is an emerging mosquito-borne alphavirus that causes clinical symptoms similar to those caused by Chikungunya virus (CHIKV), Dengue virus (DENV), and Zika virus (ZIKV). To differentiate MAYV from these viruses diagnostically, we have ... ...

Abstract	Mayaro virus (MAYV) is an emerging mosquito-borne alphavirus that causes clinical symptoms similar to those caused by Chikungunya virus (CHIKV), Dengue virus (DENV), and Zika virus (ZIKV). To differentiate MAYV from these viruses diagnostically, we have developed a portable device that integrates sample preparation with real-time, reverse-transcription, loop-mediated isothermal amplification (rRT-LAMP). First, we designed a rRT-LAMP assay targeting MAYV's non-structural protein (NS1) gene and determined the limit of detection of at least 10 viral genome equivalents per reaction. The assay was specific for MAYV, without cross-reactions with CHIKV, DENV, or ZIKV. The rRT-LAMP assay was integrated with a sample preparation device (SPD) wherein virus lysis and RNA enrichment/purification were carried out on the spot, without requiring pipetting, while subsequent real-time amplification device (RAD) enables virus detection at the point of care (POC). The functions of our platform were demonstrated using purified MAYV RNA or blood samples containing viable viruses. We have used the devices for detection of MAYV in as short as 13 min, with limit of detection to as low as 10 GEs/reaction.
MeSH term(s)	Animals ; Humans ; Zika Virus Infection/diagnosis ; Zika Virus/genetics ; Chikungunya virus/genetics ; Nucleic Acid Amplification Techniques ; Genome, Viral ; RNA, Viral/genetics
Chemical Substances	RNA, Viral
Language	English
Publishing date	2023-07-20
Publishing country	Germany
Document type	Journal Article
ZDB-ID	201093-8
ISSN	1618-2650 ; 0016-1152 ; 0372-7920
ISSN (online)	1618-2650
ISSN	0016-1152 ; 0372-7920
DOI	10.1007/s00216-023-04856-8
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Article ; Online: Characterizing the blood microbiota of omnivorous and frugivorous bats (Chiroptera: Phyllostomidae) in Casanare, eastern Colombia.

Luna, Nicolas / Muñoz, Marina / Castillo-Castañeda, Adriana / Hernandez, Carolina / Urbano, Plutarco / Shaban, Maryia / Paniz-Mondolfi, Alberto / Ramírez, Juan David

PeerJ

2023 Volume 11, Page(s) e15169

Abstract: Bats are known reservoirs of seemingly-innocuous pathogenic microorganisms (including viruses, bacteria, fungi, and protozoa), which are associated with triggering disease in other zoonotic groups. The taxonomic diversity of the bats' microbiome is ... ...

Abstract	Bats are known reservoirs of seemingly-innocuous pathogenic microorganisms (including viruses, bacteria, fungi, and protozoa), which are associated with triggering disease in other zoonotic groups. The taxonomic diversity of the bats' microbiome is likely associated with species-specific phenotypic, metabolic, and immunogenic capacities. To date, few studies have described the diversity of bat blood microbial communities. Then, this study used amplicon-based next generation sequencing of the V4 hypervariable region of the 16S-rRNA gene in blood samples from omnivorous (
MeSH term(s)	Animals ; Bartonella/genetics ; Chiroptera ; Colombia/epidemiology ; Microbiota/genetics
Language	English
Publishing date	2023-07-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2703241-3
ISSN	2167-8359 ; 2167-8359
ISSN (online)	2167-8359
ISSN	2167-8359
DOI	10.7717/peerj.15169
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Article ; Online: First case of rapidly fatal mpox from secondary (household) transmission in a kidney transplant recipient.

Fuller, Risa / Cederroth, Terra / Patel, Gopi / Reidy, Jason / Patiño, Luz Helena / Ramírez, Juan David / Bassily-Marcus, Adel / Paniz-Mondolfi, Alberto

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

2023 Volume 23, Issue 12, Page(s) 1995–1999

Abstract: In 2022, a global outbreak of mpox (formerly known as monkeypox) was reported outside of areas considered endemic for the disease, predominantly in persons identifying as men who have sex with men, gay, or bisexual. To date, 3 cases of mpox in solid ... ...

Abstract	In 2022, a global outbreak of mpox (formerly known as monkeypox) was reported outside of areas considered endemic for the disease, predominantly in persons identifying as men who have sex with men, gay, or bisexual. To date, 3 cases of mpox in solid organ transplant recipients have been published; however, no instances of secondary transmission among solid organ transplant recipients have been reported. Here, we report a case of a 53-year-old male kidney transplant recipient who contracted mpox while caring for a household contact with the disease. The patient's clinical and laboratory findings during his rapidly fatal course, autopsy findings, and genomics analysis are presented, emphasizing the need for expanded pre-exposure prophylaxis efforts in patient populations without the risk factors prioritized by public health authorities for vaccination.
MeSH term(s)	Male ; Humans ; Middle Aged ; Homosexuality, Male ; Kidney Transplantation/adverse effects ; Mpox (monkeypox) ; Sexual and Gender Minorities ; Disease Outbreaks
Language	English
Publishing date	2023-07-28
Publishing country	United States
Document type	Case Reports
ZDB-ID	2060594-8
ISSN	1600-6143 ; 1600-6135
ISSN (online)	1600-6143
ISSN	1600-6135
DOI	10.1016/j.ajt.2023.07.017
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