Fenofibrate Induces a Resolving Profile in Heart Macrophage Subsets and Attenuates Acute Chagas Myocarditis.

Chagas disease, caused by Trypanosoma cruzi, stands as the primary cause of dilated cardiomyopathy in the Americas. Macrophages play a crucial role in the heart's response to infection. Given their functional and phenotypic adaptability, manipulating specific macrophage subsets could be vital in aiding essential cardiovascular functions including tissue repair and defense against infection. PPARα are ligand-dependent transcription factors involved in lipid metabolism and inflammation regulation. However, the role of fenofibrate, a PPARα ligand, in the activation profile of cardiac macrophages as well as its effect on the early inflammatory and fibrotic response in the heart remains unexplored. The present study demonstrates that fenofibrate significantly reduces not only the serum activity of tissue damage biomarker enzymes (LDH and GOT) but also the circulating proportions of pro-inflammatory monocytes (CD11b+ LY6Chigh). Furthermore, both CD11b+ Ly6Clow F4/80high macrophages (MΦ) and recently differentiated CD11b+ Ly6Chigh F4/80high monocyte-derived macrophages (MdMΦ) shift toward a resolving phenotype (CD206high) in the hearts of fenofibrate-treated mice. This shift correlates with a reduction in fibrosis, inflammation, and restoration of ventricular function in the early stages of Chagas disease. These findings encourage the repositioning of fenofibrate as a potential ancillary immunotherapy adjunct to antiparasitic drugs, addressing inflammation to mitigate Chagas disease symptoms.

A Late Pleistocene coastal ecosystem in French Guiana was hyperdiverse relative to today.

Warmer temperatures and higher sea level than today characterized the Last Interglacial interval [Pleistocene, 128 to 116 thousand years ago (ka)]. This period is a remarkable deep-time analog for temperature and sea-level conditions as projected for 2100 AD, yet there has been no evidence of fossil assemblages in the equatorial Atlantic. Here, we report foraminifer, metazoan (mollusks, bony fish, bryozoans, decapods, and sharks among others), and plant communities of coastal tropical marine and mangrove affinities, dating precisely from a ca. 130 to 115 ka time interval near the Equator, at Kourou, in French Guiana. These communities include ca. 230 recent species, some being endangered today and/or first recorded as fossils. The hyperdiverse Kourou mollusk assemblage suggests stronger affinities between Guianese and Caribbean coastal waters by the Last Interglacial than today, questioning the structuring role of the Amazon Plume on tropical Western Atlantic communities at the time. Grassland-dominated pollen, phytoliths, and charcoals from younger deposits in the same sections attest to a marine retreat and dryer conditions during the onset of the last glacial (ca. 110 to 50 ka), with a savanna-dominated landscape and episodes of fire. Charcoals from the last millennia suggest human presence in a mosaic of modern-like continental habitats. Our results provide key information about the ecology and biogeography of pristine Pleistocene tropical coastal ecosystems, especially relevant regarding the-widely anthropogenic-ongoing global warming.

Convergent adaptation of true crabs (Decapoda: Brachyura) to a gradient of terrestrial environments.

For much of terrestrial biodiversity, the evolutionary pathways of adaptation from marine ancestors are poorly understood, and have usually been viewed as a binary trait. True crabs, the decapod crustacean infraorder Brachyura, comprise over 7,600 species representing a striking diversity of morphology and ecology, including repeated adaptation to non-marine habitats. Here, we reconstruct the evolutionary history of Brachyura using new and published sequences of 10 genes for 344 tips spanning 88 of 109 brachyuran families. Using 36 newly vetted fossil calibrations, we infer that brachyurans most likely diverged in the Triassic, with family-level splits in the late Cretaceous and early Paleogene. By contrast, the root age is underestimated with automated sampling of 328 fossil occurrences explicitly incorporated into the tree prior, suggesting such models are a poor fit under heterogeneous fossil preservation. We apply recently defined trait-by-environment associations to classify a gradient of transitions from marine to terrestrial lifestyles. We estimate that crabs left the marine environment at least seven and up to 17 times convergently, and returned to the sea from non-marine environments at least twice. Although the most highly terrestrial- and many freshwater-adapted crabs are concentrated in Thoracotremata, Bayesian threshold models of ancestral state reconstruction fail to identify shifts to higher terrestrial grades due to the degree of underlying change required. Lineages throughout our tree inhabit intertidal and marginal marine environments, corroborating the inference that the early stages of terrestrial adaptation have a lower threshold to evolve. Our framework and extensive new fossil and natural history datasets will enable future comparisons of non-marine adaptation at the morphological and molecular level. Crabs provide an important window into the early processes of adaptation to novel environments, and different degrees of evolutionary constraint that might help predict these pathways.

Neuroendocrine Neoplasms of the Head and Neck: A Case Report on an Oropharyngeal Presentation.

Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors that can appear in many different locations as neuroendocrine cells are distributed throughout the anatomy during embryonic development. This paper presents a case report of a 77-year-old woman with a rare NEN in the lateral wall of the pharynx. In addition to being very infrequent, it can be considered a second metachronous tumor since it is unrelated to a previous sinonasal NEN that the patient presented with 20 years before. We have reviewed the histological characteristics of NENs and the grading system used to determine their potential for metastasis or local invasion. NENs in the oropharynx are very infrequent and typically do not present systemic symptoms or specific local signs. The article concludes that surgical excision is typically the preferred treatment for localized NENs where complete removal is possible.

Dislocation and survival rate of dual mobility cups in revision total hip arthroplasty in patients with high risk of instability.

PURPOSE: Instability remains as an unsolved complication after revision total hip arthroplasty (rTHA). Dual mobility (DM) cups have decreased dislocation rate in rTHA; however, there are few clinical studies that evaluate the risk of dislocation after rTHA in patients with high risk of instability. METHODS: Between 2007 and 2019, 95 consecutive rTHA using a DM cup, in 93 patients with instability risk factors were retrospectively reviewed. Instability risk factors were defined as follows: deficient abductor mechanism (22.1%), previous dislocation (68.4%), Paprosky 3 acetabular bone defect (21.1%), neuromuscular disease (4.2%), lumbar spine arthrodesis (6.3%), and more than one previous surgery (33.6%). Mean follow-up was 4.3 ± 2.4 years. Clinical and radiographic parameters were reported. DM cup survival was determined using a Kaplan-Meier analysis with re-revision for any cause as the end-point. Surgical complications and re-dislocation rate was recorded. RESULTS: Seven DM cups were re-revised; three due to aseptic loosening, three due to peri-prosthetic joint infection (PJI), and one due to instability. At seven years follow-up, the survival rate of the DM cup using re-revision for any reason as the end-point was 82.4% (95% confidence interval, 66.4-98.4%). There were 12 (12.6%) complications: two (2.1%) dislocations, six (6.3%) PJI, four (4.2%) peri-prosthetic fractures. CONCLUSION: Our findings suggest DM cups are effective reducing dislocation rate in rTHA in patients with a high risk of instability, without increasing early aseptic loosening and with a low rate of dislocation. Nevertheless, longer follow-up is needed to confirm implant stability and dislocation rates in the long term.

Transcriptomic study in explanted liver from a patient with acute intermittent porphyria.

Acute intermittent porphyria (AIP) is a rare disease caused by a deficiency of hydroxymethylbilane synthase (HMBS), the third enzyme of the heme-synthesis pathway. Decreased enzymatic activity in the liver induces an overproduction of heme-precursors and acute neurological attacks. We report a 36-years-old female with AIP with a long-term history of severe, disabling, recurrent attacks, who underwent curative liver transplantation. Tissue samples from the explant were obtained for transcriptome analysis. Whole RNA was extracted and 16 gene-transcripts were selected and investigated by quantitative polymerase chain reaction. These included nine genes encoding enzymes that consecutively catalyze heme-synthesis and catabolism in the liver (ALAS1; ALAD; HMBS; UROS; UROD; CPOX; PPOX; FECH; HMOX1). Additionally, we studied genes related to inflammation (IL6; TNF) insulin signaling (PGC-1α; IGF-1; FOXO-1) and tryptophan metabolism (TDO2; IDO). Transcripts of eight house-keeping genes were co-measured for normalization. All transcripts were also measured in five control samples from healthy living liver donors. The transcriptome of the controls showed important differences between the various genes, with the first two genes of the heme-synthesis pathway, ALAS1 and ALAD showing strikingly high mRNA levels compared to the consecutive HMBS gene. Transcripts of several genes significantly differed in the AIP liver compared to controls. Transcripts of HMOX1 and UROS were increased in the AIP liver whereas transcripts of UROD; CPOX, PPOX, and TDO2 were decreased. ALAS1 expression was not increased, possibly due to hemin administered to the patient before transplantation. These results highlight several transcriptomic changes related to heme homeostasis in AIP.

The remarkable visual system of a Cretaceous crab.

True crabs (Brachyura) are one of the few groups of arthropods to evolve several types of compound eye, the origins and early evolution of which are obscure. Here, we describe details of the eyes of the Cretaceous brachyuran Callichimaera perplexa, which possessed remarkably large eyes and a highly disparate body form among brachyurans. The eyes of C. perplexa preserve internal optic neuropils and external corneal elements, and it is the first known post-Paleozoic arthropod to preserve both. Additionally, a series of specimens of C. perplexa preserve both the eyes and carapace, allowing for the calculation of the optical growth rate. C. perplexa shows the fastest optical growth rate compared with a sample of 14 species of extant brachyurans. The growth series of C. perplexa, in combination with the calculation of the interommatidial angle and eye parameter, demonstrates that it was a highly visual predator that inhabited well-lit environments.

Crab in amber reveals an early colonization of nonmarine environments during the Cretaceous.

Amber fossils provide snapshots of the anatomy, biology, and ecology of extinct organisms that are otherwise inaccessible. The best-known fossils in amber are terrestrial arthropods­principally insects­whereas aquatic organisms are rarely represented. Here, we present the first record of true crabs (Brachyura) in amber­from the Cretaceous of Myanmar [~100 to 99 million years (Ma)]. The new fossil preserves large compound eyes, delicate mouthparts, and even gills. This modern-looking crab is nested within crown Eubrachyura, or "higher" true crabs, which includes the majority of brachyuran species living today. The fossil appears to have been trapped in a brackish or freshwater setting near a coastal to fluvio-estuarine environment, bridging the gap between the predicted molecular divergence of nonmarine crabs (~130 Ma) and their younger fossil record (latest Cretaceous and Paleogene, ~75 to 50 Ma) while providing a reliable calibration point for molecular divergence time estimates for higher crown eubrachyurans.

How to become a crab: Phenotypic constraints on a recurring body plan.

A fundamental question in biology is whether phenotypes can be predicted by ecological or genomic rules. At least five cases of convergent evolution of the crab-like body plan (with a wide and flattened shape, and a bent abdomen) are known in decapod crustaceans, and have, for over 140 years, been known as "carcinization." The repeated loss of this body plan has been identified as "decarcinization." In reviewing the field, we offer phylogenetic strategies to include poorly known groups, and direct evidence from fossils, that will resolve the history of crab evolution and the degree of phenotypic variation within crabs. Proposed ecological advantages of the crab body are summarized into a hypothesis of phenotypic integration suggesting correlated evolution of the carapace shape and abdomen. Our premise provides fertile ground for future studies of the genomic and developmental basis, and the predictability, of the crab-like body form.

Exceptional preservation of comma shrimp from a mid-Cretaceous Lagerstätte of Colombia, and the origins of crown Cumacea.

Mesozoic rocks with exceptional preservation of marine arthropods are known worldwide but largely restricted to mid-high latitudes. The scarcity of assemblages with exceptional preservation in low, tropical latitudes greatly limits our understanding of the origins of several modern groups and the evolution of tropical biotas through time. Here, we report the oldest crown Cumacea, or 'comma' shrimp (Arthropoda: Eumalacostraca: Peracarida) with modern familial affinities, from a new mid-Cretaceous (95-90 Ma) Lagerstätte in tropical South America. Cumaceans have one of the poorest fossil records among marine arthropods, despite today being abundant and speciose benthic organisms associated with fine-grained sediments with high fossilization potential. Eobodotria muisca gen. et sp. nov., found in mass accumulation surfaces, preserves with detail the gut, mouth parts, thoracic legs/pereopods, pleopods, uropods bearing setae, antennal flagella and even small eyes bearing ommatidia. These features, rarely preserved in fossil crustaceans, plus the large sample size (greater than 200 individuals, 6-8 mm long), allow us to discuss phylogenetic/systematic aspects and explore possible mechanisms behind their unusual accumulation. Eobodotria bridges an approximately 165 Myr gap in the cumacean fossil record, provides a reliable calibration point for phylogenetic studies and expands our understanding of exceptional preservation in past and present tropical settings.

Palaeoecology of Voulteryon parvulus (Eucrustacea, Polychelida) from the Middle Jurassic of La Voulte-sur-Rhône Fossil-Lagerstätte (France).

Exceptional and extremely rare preservation of soft parts, eyes, or syn-vivo associations provide crucial palaeoecological information on fossil-rich deposits. Here we present exceptionally preserved specimens of the polychelidan lobster Voulteryon parvulus, from the Jurassic of La Voulte-sur-Rhône Fossil-Lagerstätte, France, bearing eyes with hexagonal and square facets, ovaries, and a unique association with epibiont thecideoid brachiopods, giving insights onto the palaeoenvironment of this Lagerstätte. The eyes, mostly covered in hexagonal facets are interpreted as either apposition eyes (poorly adapted to low-light environment) or, less likely, as refractive or parabolic superposition eyes (compatible with dysphotic palaeoenvironments). The interpretation that V. parvulus had apposition eyes suggests an allochthonous, shallow water origin. However, the presence of thecideoid brachiopod ectosymbionts on its carapace, usually associated to dim-light paleoenvironments and/or rock crevices, suggests that V. parvulus lived in a dim-light setting. This would support the less parsimonious interpretation that V. parvulus had superposition eyes. If we accept the hypothesis that V. parvulus had apposition eyes, since the La Voulte palaeoenvironment is considered deep water and had a soft substrate, V. parvulus could have moved into the La Voulte Lagerstätte setting. If this is the case, La Voulte biota would record a combination of multiple palaeoenvironments.

Miocene flooding events of western Amazonia.

There is a considerable controversy about whether western Amazonia was ever covered by marine waters during the Miocene [23 to 5 Ma (million years ago)]. We investigated the possible occurrence of Miocene marine incursions in the Llanos and Amazonas/Solimões basins, using sedimentological and palynological data from two sediment cores taken in eastern Colombia and northwestern Brazil together with seismic information. We observed two distinct marine intervals in the Llanos Basin, an early Miocene that lasted ~0.9 My (million years) (18.1 to 17.2 Ma) and a middle Miocene that lasted ~3.7 My (16.1 to 12.4 Ma). These two marine intervals are also seen in Amazonas/Solimões Basin (northwestern Amazonia) but were much shorter in duration, ~0.2 My (18.0 to 17.8 Ma) and ~0.4 My (14.1 to 13.7 Ma), respectively. Our results indicate that shallow marine waters covered the region at least twice during the Miocene, but the events were short-lived, rather than a continuous full-marine occupancy of Amazonian landscape over millions of years.

Potential Relevance of Melatonin Against Some Infectious Agents: A Review and Assessment of Recent Research.

Melatonin, a tryptophan-derived neurohormone found in animals, plants, and microbes, participates in various biological and physiological functions. Among other properties, numerous in vitro or in vivo studies have reported its therapeutic potential against many parasites, bacteria and viruses. In this concern, melatonin was found to be effective against many parasites such as Plasmodium, Toxoplasma gondii, and Trypansoma cruzi, via various mechanisms such as modulation of calcium level and/or host immune system. Likewise, a recent investigation has reported in vitro activity of melatonin against Leishmania infantum promastigotes which is the causative agent of fascinating visceral Leishmaniasis. This review was initially undertaken to summarize some facts about certain physiological and therapeutic effects of melatonin. It also reviews the effects and action mechanisms of melatonin in bacterial and viral infection besides biology of different parasites which may provide a promising strategy for control of many diseases of public health importance.

TuberQ: a Mycobacterium tuberculosis protein druggability database.

In 2012 an estimated 8.6 million people developed tuberculosis (TB) and 1.3 million died from the disease [including 320 000 deaths among human immunodeficiency virus (HIV)-positive people]. There is an urgent need for new anti-TB drugs owing to the following: the fact that current treatments have severe side effects, the increasing emergence of multidrug-resistant strains of Mycobacterium tuberculosis (Mtb), the negative drug-drug interactions with certain HIV (or other disease) treatments and the ineffectiveness against dormant Mtb. In this context we present here the TuberQ database, a novel resource for all researchers working in the field of drug development in TB. The main feature of TuberQ is to provide a druggability analysis of Mtb proteins in a consistent and effective manner, contributing to a better selection of potential drug targets for screening campaigns and the analysis of targets for structure-based drug design projects. The structural druggability analysis is combined with features related to the characteristics of putative inhibitor binding pockets and with functional and biological data of proteins. The structural analysis is performed on all available unique Mtb structures and high-quality structural homology-based models. This information is shown in an interactive manner, depicting the protein structure, the pockets and the associated characteristics for each protein. TuberQ also provides information about gene essentiality information, as determined from whole cell-based knockout experiments, and expression information obtained from microarray experiments done in different stress-related conditions. We hope that TuberQ will be a powerful tool for researchers working in TB and eventually will lead to the identification of novel putative targets and progresses in therapeutic activities. Database URL: http://tuberq.proteinq.com.ar/

Reproducing on time when temperature varies: shifts in the timing of courtship by fiddler crabs.

Many species reproduce when conditions are most favorable for the survival of young. Numerous intertidal fish and invertebrates release eggs or larvae during semilunar, large amplitude, nocturnal tides when these early life stages are best able to escape predation by fish that feed near the shore during the day. Remarkably, some species, including the fiddler crabs Uca terpsichores and Uca deichmanni, maintain this timing throughout the year as temperature, and thus the rate of embryonic development, vary. The mechanisms that allow such precision in the timing of the production of young are poorly known. A preliminary study suggested that when temperature decreases, U. terpsichores mate earlier in the tidal amplitude cycle such that larvae are released at the appropriate time. We tested this idea by studying the timing of courtship in U. terpsichores and U. deichmanni as temperature varied annually during two years, at 5 locations that differed in the temperature of the sediment where females incubate their eggs. Uca terpsichores courted earlier at locations where sediment temperature declined seasonally but not where sediment temperature remained elevated throughout the year. In contrast, clear shifts in courtship timing were not observed for U. deichmanni despite variation in sediment temperature. We discuss other mechanisms by which this species may maintain reproductive timing. These two species are likely to be affected differently by changes in the frequency and intensity of cold periods that are expected to accompany climate change.

[Malacoplakia of the seminal vesicles. Case report and particularities].

OBJECTIVE: Malacoplakia is a rare chronic granulomatous disorder that mostly affects the urogenital system. This article describes a case of uncommon location of this disease at the level of the seminal vesicles and the clinical, imaging and histological particularities of this medical entity. METHOD: We report the case of a 69 year-old male consulting for constitutional syndrome that presented a pelvic tumor on the image studies, possibly arising in the seminal vesicles. RESULTS: The diagnosis was made after performing transrectal ultrasound and seminal vesicles biopsy by the pathognomonic histological findings of Michaelis Gutmann bodies. The presence of E. Coli in urine culture in our patient justified the use of a long-term antibiotic therapy such as quinolones with very good results. CONCLUSION: Malacoplakia of the seminal vesicles is an extremely rare condition, sometimes with non-specific clinical presentation. Its diagnosis is histological and it has good response to prolonged antibiotic therapy with a benign outcome.

Malacoplaquia de vesículs seminales. Presentación de un caso clínico y particularidades / Malacoplakia of the seminal vesicles. Case report and particularities

OBJETIVO: La malacoplaquia es un proceso inflamatorio granulomatoso crónico poco frecuente siendo el aparato genitourinario el asiento más frecuente de esta enfermedad. Se describe un caso que afecta a vesículas seminales con sus particularidades clínicas, diagnósticas e histológicas de esta entidad. MÉTODO: Varón, de 69 años ingresado en otro servicio por síndrome constitucional que tras la realización de pruebas de imagen (tomografía computerizada) se detecta una masa pélvica de posible origen en vesículas seminales. RESULTADOS: Se realiza ecografía transrectal y biopsia de vesículas seminales que en el estudio histológico evidencian la presencia de cuerpos de Michaelis Gutmann patognomónicos de malacoplaquia. El urocultivo fue positivo a Escherichia Coli, infección frecuentemente asociada a esta enfermedad y cuyo tratamiento de elección es la antibioterapia a largo plazo con fluoroquinolonas, que consiguió buenos resultados en nuestro caso. CONCLUSIÓN: La malacoplaquia localizada en vesículas seminales es una entidad extremadamente rara, con clínica a veces inespecífica, de diagnóstico histológico y tratamiento médico antibiótico con una evolución benigna(AU)

OBJECTIVE: Malacoplakia is a rare chronic granulomatous disorder that mostly affects the urogenital system. This article describes a case of uncommon location of this disease at the level of the seminal vesicles and the clinical, imaging and histological particularities of this medical entity. METHOD: We report the case of a 69 year-old male consulting for constitutional syndrome that presented a pelvic tumor on the image studies, possibly arising in the seminal vesicles. RESULTS: The diagnosis was made after performing transrectal ultrasound and seminal vesicles biopsy by the pathognomonic histological findings of Michaelis Gutmann bodies. The presence of E. Coli in urine culture in our patient justified the use of a long-term antibiotic therapy such as quinolones with very good results. CONCLUSION: Malacoplakia of the seminal vesicles is an extremely rare condition, sometimes with non-specific clinical presentation. Its diagnosis is histological and it has good response to prolonged antibiotic therapy with a benign outcome(AU)

Comprehensive prediction model of urinary incontinence one year following robot-assisted radical prostatectomy.

OBJECTIVES: Urinary incontinence (UI) still remains one of the major functional complications after robot-assisted radical prostatectomy (RARP). As the cause for UI is multifactorial, it is quite difficult to make a prediction preoperatively. Considering intraoperative and postoperative risk factors, besides the preoperative ones, we designed an incontinence prediction model, administered 1 month after the surgery, in order to identify incontinent patients at 1 year. PATIENTS AND METHODS: We retrospectively reviewed 244 patients who underwent RARP at our institution. Only 209 patients had sufficient data, a 1-year follow-up and were continent preoperatively. The association of UI with the risk factors was assessed by univariable and multivariable regression models. RESULTS: There was a 17.2% global UI rate at 1 year after RARP. Only age-adjusted Charlson comorbidity index, erectile function assessed by International Index of Erectile Function-5, prostate volume, nerve-sparing status and 24-hour urine loss at 1 month correlated with UI (p = 0.032, 0.009, 0.031, 0.018 and <0.001, respectively). The accuracy of the prediction model of UI was 92.8% (c-index), with an area under the curve of 91.9%. CONCLUSION: Age-adjusted Charlson comorbidity index, International Index of Erectile Function-5, prostate volume, nerve-sparing status and 24-hour urine loss at 1 month after RARP can predict an individual's risk of UI at 1 year after RARP with good accuracy. Further external validation is required in order to generalize the use of this model.