Interaction between poly(A)-binding protein PABPC4 and nuclear receptor corepressor NCoR1 modulates a metabolic stress response.

Mitochondria are organelles known primarily for generating ATP via the oxidative phosphorylation process. Environmental signals are sensed by whole organisms or cells and markedly affect this process, leading to alterations in gene transcription and, consequently, changes in mitochondrial function and biogenesis. The expression of mitochondrial genes is finely regulated by nuclear transcription factors, including nuclear receptors and their coregulators. Among the best-known coregulators is the nuclear receptor corepressor 1 (NCoR1). Muscle-specific knockout of NCoR1 in mice induces an oxidative phenotype, improving glucose and fatty acid metabolism. However, the mechanism by which NCoR1 is regulated remains elusive. In this work, we identified the poly(A)-binding protein 4 (PABPC4) as a new NCoR1 interactor. Unexpectedly, we found that silencing of PABPC4 induced an oxidative phenotype in both C2C12 and MEF cells, as indicated by increased oxygen consumption, mitochondria content, and reduced lactate production. Mechanistically, we demonstrated that PABPC4 silencing increased the ubiquitination and consequent degradation of NCoR1, leading to the derepression of PPAR-regulated genes. As a consequence, cells with PABPC4 silencing had a greater capacity to metabolize lipids, reduced intracellular lipid droplets, and reduced cell death. Interestingly, in conditions known to induce mitochondrial function and biogenesis, both mRNA expression and PABPC4 protein content were markedly reduced. Our study, therefore, suggests that the lowering of PABPC4 expression may represent an adaptive event required to induce mitochondrial activity in response to metabolic stress in skeletal muscle cells. As such, the NCoR1-PABPC4 interface might be a new road to the treatment of metabolic diseases.

Worldwide forest surveys reveal forty-three new species in Phytophthora major Clade 2 with fundamental implications for the evolution and biogeography of the genus and global plant biosecurity.

During 25 surveys of global Phytophthora diversity, conducted between 1998 and 2020, 43 new species were detected in natural ecosystems and, occasionally, in nurseries and outplantings in Europe, Southeast and East Asia and the Americas. Based on a multigene phylogeny of nine nuclear and four mitochondrial gene regions they were assigned to five of the six known subclades, 2a-c, e and f, of Phytophthora major Clade 2 and the new subclade 2g. The evolutionary history of the Clade appears to have involved the pre-Gondwanan divergence of three extant subclades, 2c, 2e and 2f, all having disjunct natural distributions on separate continents and comprising species with a soilborne and aquatic lifestyle and, in addition, a few partially aerial species in Clade 2c; and the post-Gondwanan evolution of subclades 2a and 2g in Southeast/East Asia and 2b in South America, respectively, from their common ancestor. Species in Clade 2g are soilborne whereas Clade 2b comprises both soil-inhabiting and aerial species. Clade 2a has evolved further towards an aerial lifestyle comprising only species which are predominantly or partially airborne. Based on high nuclear heterozygosity levels ca. 38 % of the taxa in Clades 2a and 2b could be some form of hybrid, and the hybridity may be favoured by an A1/A2 breeding system and an aerial life style. Circumstantial evidence suggests the now 93 described species and informally designated taxa in Clade 2 result from both allopatric non-adaptive and sympatric adaptive radiations. They represent most morphological and physiological characters, breeding systems, lifestyles and forms of host specialism found across the Phytophthora clades as a whole, demonstrating the strong biological cohesiveness of the genus. The finding of 43 previously unknown species from a single Phytophthora clade highlight a critical lack of information on the scale of the unknown pathogen threats to forests and natural ecosystems, underlining the risk of basing plant biosecurity protocols mainly on lists of named organisms. More surveys in natural ecosystems of yet unsurveyed regions in Africa, Asia, Central and South America are needed to unveil the full diversity of the clade and the factors driving diversity, speciation and adaptation in Phytophthora. Taxonomic novelties: New species: Phytophthora amamensis T. Jung, K. Kageyama, H. Masuya & S. Uematsu, Phytophthora angustata T. Jung, L. Garcia, B. Mendieta-Araica, & Y. Balci, Phytophthora balkanensis I. Milenkovic, Z. Tomic, T. Jung & M. Horta Jung, Phytophthora borneensis T. Jung, A. Durán, M. Tarigan & M. Horta Jung, Phytophthora calidophila T. Jung, Y. Balci, L. Garcia & B. Mendieta-Araica, Phytophthora catenulata T. Jung, T.-T. Chang, N.M. Chi & M. Horta Jung, Phytophthora celeris T. Jung, L. Oliveira, M. Tarigan & I. Milenkovic, Phytophthora curvata T. Jung, A. Hieno, H. Masuya & M. Horta Jung, Phytophthora distorta T. Jung, A. Durán, E. Sanfuentes von Stowasser & M. Horta Jung, Phytophthora excentrica T. Jung, S. Uematsu, K. Kageyama & C.M. Brasier, Phytophthora falcata T. Jung, K. Kageyama, S. Uematsu & M. Horta Jung, Phytophthora fansipanensis T. Jung, N.M. Chi, T. Corcobado & C.M. Brasier, Phytophthora frigidophila T. Jung, Y. Balci, K. Broders & I. Milenkovic, Phytophthora furcata T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora inclinata N.M. Chi, T. Jung, M. Horta Jung & I. Milenkovic, Phytophthora indonesiensis T. Jung, M. Tarigan, L. Oliveira & I. Milenkovic, Phytophthora japonensis T. Jung, A. Hieno, H. Masuya & J.F. Webber, Phytophthora limosa T. Corcobado, T. Majek, M. Ferreira & T. Jung, Phytophthora macroglobulosa H.-C. Zeng, H.-H. Ho, F.-C. Zheng & T. Jung, Phytophthora montana T. Jung, Y. Balci, K. Broders & M. Horta Jung, Phytophthora multipapillata T. Jung, M. Tarigan, I. Milenkovic & M. Horta Jung, Phytophthora multiplex T. Jung, Y. Balci, K. Broders & M. Horta Jung, Phytophthora nimia T. Jung, H. Masuya, A. Hieno & C.M. Brasier, Phytophthora oblonga T. Jung, S. Uematsu, K. Kageyama & C.M. Brasier, Phytophthora obovoidea T. Jung, Y. Balci, L. Garcia & B. Mendieta-Araica, Phytophthora obturata T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora penetrans T. Jung, Y. Balci, K. Broders & I. Milenkovic, Phytophthora platani T. Jung, A. Pérez-Sierra, S.O. Cacciola & M. Horta Jung, Phytophthora proliferata T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora pseudocapensis T. Jung, T.-T. Chang, I. Milenkovic & M. Horta Jung, Phytophthora pseudocitrophthora T. Jung, S.O. Cacciola, J. Bakonyi & M. Horta Jung, Phytophthora pseudofrigida T. Jung, A. Durán, M. Tarigan & M. Horta Jung, Phytophthora pseudoccultans T. Jung, T.-T. Chang, I. Milenkovic & M. Horta Jung, Phytophthora pyriformis T. Jung, Y. Balci, K.D. Boders & M. Horta Jung, Phytophthora sumatera T. Jung, M. Tarigan, M. Junaid & A. Durán, Phytophthora transposita T. Jung, K. Kageyama, C.M. Brasier & H. Masuya, Phytophthora vacuola T. Jung, H. Masuya, K. Kageyama & J.F. Webber, Phytophthora valdiviana T. Jung, E. Sanfuentes von Stowasser, A. Durán & M. Horta Jung, Phytophthora variepedicellata T. Jung, Y. Balci, K. Broders & I. Milenkovic, Phytophthora vietnamensis T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora ×australasiatica T. Jung, N.M. Chi, M. Tarigan & M. Horta Jung, Phytophthora ×lusitanica T. Jung, M. Horta Jung, C. Maia & I. Milenkovic, Phytophthora ×taiwanensis T. Jung, T.-T. Chang, H.-S. Fu & M. Horta Jung. Citation: Jung T, Milenkovic I, Balci Y, Janousek J, Kudlácek T, Nagy ZÁ, Baharuddin B, Bakonyi J, Broders KD, Cacciola SO, Chang T-T, Chi NM, Corcobado T, Cravador A, Dordevic B, Durán A, Ferreira M, Fu C-H, Garcia L, Hieno A, Ho H-H, Hong C, Junaid M, Kageyama K, Kuswinanti T, Maia C, Májek T, Masuya H, Magnano di San Lio G, Mendieta-Araica B, Nasri N, Oliveira LSS, Pane A, Pérez-Sierra A, Rosmana A, Sanfuentes von Stowasser E, Scanu B, Singh R, Stanivukovic Z, Tarigan M, Thu PQ, Tomic Z, Tomsovský M, Uematsu S, Webber JF, Zeng H-C, Zheng F-C, Brasier CM, Horta Jung M (2024). Worldwide forest surveys reveal forty-three new species in Phytophthora major Clade 2 with fundamental implications for the evolution and biogeography of the genus and global plant biosecurity. Studies in Mycology 107: 251-388. doi: 10.3114/sim.2024.107.04.

Tobacco advertising and oral health among never smokers: the mediating role of secondhand smoke exposure.

OBJECTIVE: To determine whether the association between tobacco advertising (TA) exposure and poor self-rated oral health (SROH) is mediated through secondhand smoke (SHS) exposure in Brazilian adults who have never smoked. METHODS: Secondary cross-sectional analysis of The Brazilian National Health Survey 2019 data. The daily, weekly, or monthly exposure to SHS at home or at work was set as the mediator. Mediation analysis within a counterfactual approach used adjusted binary logistic regressions for both poor SROH and SHS exposure, to estimate the natural direct effect (NDE), natural indirect effect (NIE) through SHS exposure, and marginal total effect (MTE) of TA exposure on poor SROH. To assess the robustness of the results, we calculated the E-value for the MTE. RESULTS: The sample comprised 53,295 never smoker adults. The MTE of TA exposure on poor SROH was 1.09 (1.03, 1.16), with the indirect effect through SHS exposure responsible for only 16.6% of the total (NIE: 1.01 [1.01, 1.02] and NDE: 1.08 [1.02, 1.14]). An effect of 1.42 would be required for an unmeasured confounder to explain away the association between TA and SROH. CONCLUSION: More individuals exposed to TA have poor SROH than those unexposed, with secondhand smoke exposure explaining only a small portion of this effect. Upstream tobacco policies should consider oral health outcomes.

Oral maxillofacial surgeons and Orthodontists' perceptions about anterior inferior crowding and indications of mandibular third molar extraction.

BACKGROUND: There are still many doubts about anterior inferior crowding and indications of mandibular third molar extraction, although it is very studied subject in the literature. The aim of this study was to evaluate the perceptions of oral maxillofacial surgeons (OMFSs) and orthodontists about anterior inferior crowding and indications of mandibular third molar extraction. MATERIAL AND METHODS: A web-based survey was developed and sent to professionals in order to collect their opinion about the fact that third lower molars cause crowding and questions about the indication of third molars for orthodontic treatment. Descriptive analysis was performed and Chi-square or G tests were applied with a 95% confidence interval. RESULTS: The study included a total of 218 participants, of whom 115 were OMFSs and 103 were orthodontists. The results showed that 56.5% of OMFSs and 35.0% of orthodontists believe that the lower third molars cause anterior inferior crowding (p<0.001). A total of 91.3% of OMFSs and 70.9% of orthodontists indicate the extraction of lower third molars to aid orthodontic treatment (p<0.001). CONCLUSIONS: It can be concluded that in being an oral maxillofacial surgeon, a higher odds ratio is observed to consider that lower third molars cause dental crowding compared to those who are orthodontist. The indication of exodontia of lower third molars for orthodontic treatment was more frequent among OMFSs when compared to orthodontists.

Interactions among sucrose and concentrations of serum fetal bovine on the cryopreservation of somatic cells derived from red-rumped agoutis.

BACKGROUND: The synergistic action among the different extracellular cryoprotectants could improve somatic cell quality after thawing and provide bases for the formation of biobanks for red-rumped agoutis. OBJECTIVE: This study evaluated the interactions among sucrose (SUC) and concentrations of serum fetal bovine (FBS) on the cryopreservation of somatic cells derived from red-rumped agoutis. MATERIALS AND METHODS: Cells were cryopreserved with 10% dimethyl sulfoxide and different concentrations of FBS (10%, 40%, and 90%) with or without 0.2 M SUC, totaling six comparison groups. Non-cryopreserved cells were used as a control. Cells were evaluated for viability, metabolic activity, proliferative activity, reactive oxygen species (ROS), mitochondrial membrane potential and apoptosis levels. RESULTS: No difference was observed among cryopreserved with DMSO containing (10FBS, 10FBS-SUC, 40FBS, 40FBS-SUC, 90FBS, 90FBS-SUC) and non-cryopreserved groups for viability, metabolic activity, proliferative activity, and ROS levels. Interestingly, only cells cryopreserved with 90% FBS and SUC maintained the mitochondrial membrane potential like the control. This indicates that at high concentrations of FBS, SUC contributes to the maintenance of this parameter in cryopreserved cells. Moreover, at concentrations of 10% and 40% of FBS, SUC contributed to the maintenance of viability evaluated by the levels of apoptosis evaluated after thawing. In summary, we verified that 90% FBS and 0.2 M SUC promote greater ability of cells after thawing. Additionally, SUC positively acts in cryopreservation solutions containing 10% and 40% FBS. CONCLUSION: This information is essential to an understanding of the mechanisms involved in the interactions of extracellular cryoprotectants in somatic cell cryopreservation solutions of red-rumped agoutis. DOI: 10.54680/fr23210110212.

Adverse reactions to the injection of face and neck aesthetic filling materials: a systematic review.

BACKGROUND: Adverse reactions, caused during the inflammation and healing process, or even later, can be induced by the injection of dermal filler and can present a variety of clinical and histological characteristics. In this study we aimed to review the adverse reactions associated with the injection of aesthetic filling materials in the face and neck. MATERIAL AND METHODS: The review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Studies published that mentioned adverse reactions in patients with aesthetic filling materials in the face or neck were included. Risk of bias was assessed using the Joanna Briggs Institute appraisal tool. After a 2-step selection process, 74 studies were included: 51 case reports, 18 serial cases, and five cohorts. RESULTS: A total of 303 patients from 20 countries were assessed. Lesions were more prevalent in the lip (18%), nasolabial folds (13%), cheeks (13%), chin (10%), submental (8%), glabella (7%), and forehead (6%). Histopathological analysis revealed a foreign body granuloma in 87.1% of the patients, 3% inflammatory granuloma, 3% lipogranuloma, 2.3% xanthelasma-like reaction, 1% fibrotic reaction, 0.7% amorphous tissues, 0.7% xanthelasma, 0.3% sclerosing lipogranuloma, 0.3% siliconoma, and 0.3% foreign body granuloma with scleromyxedema. In addition, two patients displayed keratoacanthoma and two others displayed sarcoidosis after cutaneous filling. The most commonly used materials were silicone fillers (19.7%), hyaluronic acid (15.5%), and hydroxyethyl methacrylate/ethyl methacrylate suspended in hyaluronic acid acrylic hydrogel (5.6%). All patients were treated, and only 12 had prolonged complications. CONCLUSIONS: There is evidence that adverse reaction can be caused by different fillers in specific sites on the face. Although foreign body granuloma was the most common, other adverse lesions were diagnosed, exacerbating systemic diseases. In this way, we reinforce the importance of previous systemic evaluations and histopathological analyses for the correct diagnosis of lesions.

Evaluation of remote teaching in master programs in the Oral Pathology and Oral Medicine during the COVID-19 pandemic. Brazilian multicentric study.

BACKGROUND: With the COVID-19 pandemic, there was a need to adopt online teaching methods in a generalized and sudden way, a situation that led to unprecedented changes in the routine of post-graduate students and research development. This study aimed to analyze the evaluation of remote teaching by graduates of master's degrees and advisors in master's programs in the Oral Pathology and Oral Medicine who needed to adapt to a remote teaching methodology in the pandemic. MATERIAL AND METHODS: This quantitative study evaluated the remote teaching in the perception of master's graduates and advisors from postgraduate programs in Oral Pathology and Oral Medicine. Data were collected through an online Google forms® questionnaire. RESULTS: Participated in the study 14 master graduates and 14 master's advisors. Master graduates evaluated that the professors had a good performance (p=0.001), that the duration of the classes was adequate (p=0.015), that the interaction with professors was satisfactory (p=0.007), that they had good interaction with the advisor (p=0.001), that they were satisfied with the remote guidance process (p=0.038) and that face-to-face practical activities were missed (p=0.002). Master's advisors reported satisfaction with remote teaching, good adaptation (p=0.018) and motivation for remote teaching (p=0.016), they evaluated that students were cooperative in activities (p=0.019) and that face-to-face practical activities were missed (p=0.002). CONCLUSIONS: Despite the difficulties, remote teaching proved to be an effective alternative to face-to-face teaching.

Oral paracoccidioidomycosis: a retrospective study of 95 cases from a single center and literature review.

BACKGROUND: The ecoepidemiological panorama of paracoccidioidomycosis (PCM) is dynamic and still ongoing in Brazil. In particular, data about the oral lesions of PCM are barely explored. The aim of this study was to report the clinicopathological features of individuals diagnosed with oral PCM lesions at an oral and maxillofacial pathology service in Rio de Janeiro, Brazil, in the light of a literature review. MATERIAL AND METHODS: A retrospective study was conducted on oral biopsies obtained from 1958 to 2021. Additionally, electronic searches were conducted in PubMed, Embase, Scopus, Web of Science, Latin American and Caribbean Center on Health Sciences Information, and Brazilian Library of Dentistry to gather information from large case series of oral PCM. RESULTS: Ninety-five cases of oral PCM were surveyed. The manifestations were more frequent among males (n=86/90.5%), middle-aged/older adults (n=54/58.7%), and white individuals (n=40/51.9%). The most commonly affected sites were the gingiva/alveolar ridge (n=40/23.4%) and lip/labial commissure (n=33/19.3%); however, one (n=40/42.1%) or multiple sites (n=55/57.9%) could also be affected. In 90 (94.7%) patients, "mulberry-like" ulcerations/moriform appearance were observed. Data from 21 studies (1,333 cases), mostly Brazilian (90.5%), revealed that men (92.4%; male/female: 11.8:1) and individuals in the fifth and sixth decades of life were the most affected (range: 7-89 years), with the gingiva/alveolar ridge, palate, and lips/labial commissure being the sites most frequently affected. CONCLUSIONS: The features of oral PCM lesions are similar to those reported in previous studies from Latin America. Clinicians should be aware of the oral manifestations of PCM, with emphasis on the clinicodemographic aspects and differential diagnoses, especially considering the phenomenon of the emergence of reported cases in rural and/or urban areas of Brazil.

Constructing evidence-based clinical intrapartum care algorithms for decision-support tools.

AIM: To describe standardised iterative methods used by a multidisciplinary group to develop evidence-based clinical intrapartum care algorithms for the management of uneventful and complicated labours. POPULATION: Singleton, term pregnancies considered to be at low risk of developing complications at admission to the birthing facility. SETTING: Health facilities in low- and middle-income countries. SEARCH STRATEGY: Literature reviews were conducted to identify standardised methods for algorithm development and examples from other fields, and evidence and guidelines for intrapartum care. Searches for different algorithm topics were last updated between January and October 2020 and included a combination of terms such as 'labour', 'intrapartum', 'algorithms' and specific topic terms, using Cochrane Library and MEDLINE/PubMED, CINAHL, National Guidelines Clearinghouse and Google. CASE SCENARIOS: Nine algorithm topics were identified for monitoring and management of uncomplicated labour and childbirth, identification and management of abnormalities of fetal heart rate, liquor, uterine contractions, labour progress, maternal pulse and blood pressure, temperature, urine and complicated third stage of labour. Each topic included between two and four case scenarios covering most common deviations, severity of related complications or critical clinical outcomes. CONCLUSIONS: Intrapartum care algorithms provide a framework for monitoring women, and identifying and managing complications during labour and childbirth. These algorithms will support implementation of WHO recommendations and facilitate the development by stakeholders of evidence-based, up to date, paper-based or digital reminders and decision-support tools. The algorithms need to be field tested and may need to be adapted to specific contexts. TWEETABLE ABSTRACT: Evidence-based intrapartum care clinical algorithms for a safe and positive childbirth experience.

Lytic to temperate switching of viral communities.

Microbial viruses can control host abundances via density-dependent lytic predator-prey dynamics. Less clear is how temperate viruses, which coexist and replicate with their host, influence microbial communities. Here we show that virus-like particles are relatively less abundant at high host densities. This suggests suppressed lysis where established models predict lytic dynamics are favoured. Meta-analysis of published viral and microbial densities showed that this trend was widespread in diverse ecosystems ranging from soil to freshwater to human lungs. Experimental manipulations showed viral densities more consistent with temperate than lytic life cycles at increasing microbial abundance. An analysis of 24 coral reef viromes showed a relative increase in the abundance of hallmark genes encoded by temperate viruses with increased microbial abundance. Based on these four lines of evidence, we propose the Piggyback-the-Winner model wherein temperate dynamics become increasingly important in ecosystems with high microbial densities; thus 'more microbes, fewer viruses'.

Central angiotensinergic mechanisms in female spontaneously hypertensive rats treated with estradiol.

Estrogens reduce 0.3 M NaCl intake and palatability in a widely used model of essential hypertension, the spontaneously hypertensive rats (SHRs). Here we investigated whether the inhibitory effects of ß-estradiol (E2, 10 µg/kg b.w. subcutaneously for 8 days) on water deprived partially-rehydrated (WD-PR) ovariectomized (OVX) adult female SHRs (fSHRs, n = 4-10/group) are related to interferences on brain angiotensin II AT1 receptors (AT1r). After WD-PR, E2 reduced 0.3 M NaCl intake (1.3 ± 0.6, vs. vehicle: 3.5 ± 1.2 ml/30 min), the number of hedonic responses to intraoral NaCl infusion (57 ± 11, vs. vehicle: 176 ± 32/min), and the relative angiotensin AT1r (Agtr1a) mRNA expression in the hypothalamus. Losartan (AT1r antagonist, 100 µg) intracerebroventricularly in OVX fSHRs treated with vehicle subcutaneously abolished 0.3 M NaCl intake (0.1 ± 0.1 ml/30 min) and only transiently reduced hedonic responses to intraoral NaCl. Losartan combined with E2 decreased the number of hedonic and increased the number of aversive responses to intraoral NaCl and abolished 0.3 M NaCl intake. E2 also reduced the pressor and dipsogenic responses to intracerebroventricular angiotensin II. The results suggest that AT1r activation increases palatability and induces NaCl intake in WD-PR fSHRs. E2 reduced hypothalamic Agtr1a mRNA expression, which may account for the effects of E2 on NaCl intake and palatability and intracerebroventricular angiotensin II-induced pressor and dipsogenic responses in OVX fSHRs. Future studies considering natural fluctuations in estrogen secretion might help to determine the degree of such interference in brain neuronal activity.

A health survey of the reef forming scleractinian cold-water corals Lophelia pertusa and Madrepora oculata in a remote submarine canyon on the European continental margin, NE Atlantic.

Monitoring of cold-water corals (CWCs) for pathogens and diseases is limited due to the environment, protected nature of the corals and their habitat and as well as the challenging and sampling effort required. It is recognised that environmental factors such as temperature and pH can expedite the ability of pathogens to cause diseases in cold-water corals therefore the characterisation of pathogen diversity, prevalence and associated pathologies is essential. The present study combined histology and polymerase chain reaction (PCR) diagnostic techniques to screen for two significant pathogen groups (bacteria of the genus Vibrio and the protozoan Haplosporidia) in the dominant NE Atlantic deep-water framework corals Lophelia pertusa (13 colonies) and Madrepora oculata (2 colonies) at three sampling locations (canyon head, south branch and the flank) in the Porcupine Bank Canyon (PBC), NE Atlantic. One M. oculata colony and four L. pertusa colonies were collected from both the canyon flank and the south branch whilst five L. pertusa colonies were collected from the canyon head. No pathogens were detected in the M. oculata samples. Neither histology nor PCR detected Vibrio spp. in L. pertusa, although Illumina technology used in this study to profile the CWCs microbiome, detected V. shilonii (0.03%) in a single L. pertusa individual, from the canyon head, that had also been screened in this study. A macroborer was observed at a prevalence of 0.07% at the canyon head only. Rickettsiales-like organisms (RLOs) were visualised with an overall prevalence of 40% and with a low intensity of 1 to 4 (RLO) colonies per individual polyp by histology. L. pertusa from the PBC canyon head had an RLO prevalence of 13.3% with the highest detection of 26.7% recorded in the south branch corals. Similarly, unidentified cells observed in L. pertusa from the south branch (20%) were more common than those observed in L. pertusa from the canyon head (6.7%). No RLOs or unidentified cells were observed in corals from the flank. Mean particulate organic matter concentration is highest in the south branch (2,612 µg l-1) followed by the canyon head (1,065 µg l-1) and lowest at the canyon flank (494 µg l-1). Although the route of pathogen entry and the impact of RLO infection on L. pertusa is unclear, particulate availability and the feeding strategies employed by the scleractinian corals may be influencing their exposure to pathogens. The absence of a pathogen in M. oculata may be attributed to the smaller number of colonies screened or the narrower diet in M. oculata compared to the unrestricted diet exhibited in L. pertusa, if ingestion is a route of entry for pathogen groups. The findings of this study also shed some light on how environmental conditions experienced by deep sea organisms and their life strategies may be limiting pathogen diversity and prevalence.

Effects of the bovine SLICK1 mutation in PRLR on sweat gland area, FOXA1 abundance, and global gene expression in skin.

The SLICK1 mutation in the prolactin receptor (PRLR) results in a short-hair coat and increased ability to regulate body temperature during heat stress. It is unclear whether the mutation affects capacity for sweating. The objective of this observational study was to evaluate whether the SLICK1 mutation in PRLR alters characteristics of skin related to sweat gland abundance or function. Skin biopsies from 31 Holstein heifers, including 14 wild-type (SL-/-) and 17 heterozygous slick (SL+/-), were subjected to histological analysis to determine the percent of the surface area of skin sections that are occupied by sweat glands. We detected no effect of genotype on this variable. Immunohistochemical analysis of the forkhead transcription factor A1 (FOXA1), a protein essential for sweating in mice, from 6 SL-/- and 6 SL+/- heifers indicated twice as much FOXA1 in sweat glandular epithelia of SL+/- heifers as in SL-/- heifers. Results from RNA sequencing of skin biopsies from 5 SL-/- and 7 SL+/- heifers revealed few genes that were differentially expressed and none that have been associated with sweat gland development or function. In conclusion, results do not support the idea that the SLICK1 mutation changes the abundance of sweat glands in skin, but do show that functional properties of sweat glands, as indicated by increased abundance of immunoreactive FOXA1, are modified by inheritance of the mutation in PRLR.

HIV-related non-Hodgkin lymphomas affecting the oral cavity: a clinicopathologic study of 11 cases.

BACKGROUND: HIV-related non-Hodgkin lymphomas of the oral cavity are rare lesions with aggressive clinical behaviour. The aim of this study is to describe the clinicopathological features of a series of HIV-related oral non-Hodgkin lymphomas. MATERIAL AND METHODS: Eleven cases of oral lymphomas affecting HIV-positive patients were retrieved from 2012 to 2019. Clinicopathological features regarding age, sex, tumour location, clinical presentation, laboratory findings, disease stage and follow-up were obtained. Histologic, immunohistochemical and in situ hybridization for EBV detection were done for diagnosis confirmation. Overall survival was estimated by Kaplan-Meier curve. RESULTS: Males predominated, with a mean age of 40.3 years-old. Maxilla and mandible were the mostly affected. Plasmablastic lymphoma and diffuse large B-cell lymphoma not otherwise specified (NOS) were the main histological types. Lesions presented as reddish ulcerated swellings, representing the first sign of AIDS in six cases. Stage IV were common (7 cases) and the mean HIV viral load was 10,557 copies/mL, with a mean of 266 CD4+ cells/mm3, 1,278 CD8+ cells/mm3 and a CD4+/CD8+ ratio of 0.26. Eight patients died of the disease (72.7%). Overall survival revealed that 78.2% of the patients died after 21 months of follow-up. CONCLUSIONS: HIV-related oral lymphomas present a poor prognosis usually diagnosed in advanced stages and in our series plasmablastic lymphoma was the most common subtype.

Lactobacillus paracasei DTA81, a cholesterol-lowering strain having immunomodulatory activity, reveals gut microbiota regulation capability in BALB/c mice receiving high-fat diet.

AIMS: In-vitro/In-vivo evaluation of cholesterol-lowering probiotic strain Lactobacillus paracasei DTA81 and the possible connection with the gut microbiota modulation. METHODS AND RESULTS: In the present study, strain DTA81 has been evaluated for the possible influence on blood lipid and glucose concentrations, modulation of the immune system, gastrointestinal survivability and modulation of gut microbiota in BALB/c mice receiving a high-fat diet. After 6 weeks of treatment, a significant reduction of total cholesterol and fasting blood sugar (FBS) among animals treated with L. paracasei DTA81 has been recorded. Comparison of colon tissue levels of different cytokines revealed a significant reduction of the inflammatory cytokine interleukin-6. The comparison of gut microbiota using the 16S rRNA approach indicated that the treatment with L. paracasei DTA81 significantly increased the taxa Bacteroidetes and Coprococcus. Moreover, the genome of DTA81 was sequenced for the in-silico assessment, and the analysis indicated the presence of cholesterol assimilation-related genes as well as the absence of negative traits such as transmissible antibiotic resistance genes, plasmids and prophage regions. CONCLUSION: The outcome of this study revealed the in-vitro and in-vivo properties of L. paracasei DTA81 and the possible mechanism between consumption of this strain, the abundance of Bacteriodetes/Coprococcus taxa, immunomodulatory activity and the subsequent reduction of cholesterol/FBS in BALB/c mice. SIGNIFICANCE AND IMPACT OF THE STUDY: Lactobacillus paracasei DTA81 as a non-pharmacological potential probiotic supplement can influence metabolic homeostasis in individuals, particularly those adopting high-fat diets, and it can contribute to reduce coronary heart disease.

Recombinogenic, genotoxic, and cytotoxic effects of azathioprine using in vivo assays.

Azathioprine (Aza) is a purine antimetabolite immunosuppressant that is widely employed for immunosuppressive therapy in post-transplant recipients or patients with autoimmune diseases. Chronic use of immunosuppressants might produce several side effects, including a high rate of neoplasms in these patients. Considering that genotoxic effects are associated with an increased risk of developing cancer, the aim of this study was to examine the recombinogenic, genotoxic, and cytotoxic effects of Aza using Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster, as well as comet and micronucleus assays in mouse bone marrow cells. Further, the adverse effects of Aza were determined in mouse hepatic and renal tissues using histopathological analysis. Data demonstrated that Aza induced significant increased genotoxicity in D. melanogaster and mouse bone marrow cells at all concentrations tested. Homologous recombination was the predominant genotoxic event noted for the first time to be initiated by Aza in SMART. In histopathological analysis, Aza did not show any marked toxic activity in mouse hepatic and renal tissues. Therefore, the high rate of neoplasms reported in patients with long-term use of Aza may be attributed, at least partially, to the genotoxic action of this drug.

Persistent inflammation, immunosuppression and catabolism syndrome (PICS) in critically ill children is associated with clinical outcomes: a prospective longitudinal study.

BACKGROUND: Persistent inflammation, immunosuppression and catabolism syndrome (PICS) has been described in critically ill adults and may contribute to unfavourable outcomes. The present study aimed to describe and characterise PICS in critically ill children (PICS-ped) and to verify its association with clinical outcomes. METHODS: A prospective longitudinal study was conducted in a paediatric intensive care unit (PICU) with children aged between 3 months and 15 years. PICS-ped, based on adult definition, was described. PICS-ped was defined as PICU length of stay >14 days; C-reactive protein > 10.0 mg L-1 ; lymphocytes <25%; and any reduction of mid-upper arm circumference Z-score. Clinical, demographic, nutritional status, nutrition therapy parameters and clinical outcomes were assessed. Statistical analysis comprised Mann-Whitney and Fisher's chi-squared tests, as well as logistic and Cox regression. P < 0.05 was considered statistically significant. RESULTS: In total, 153 children were included, with a median age of 51.7 months (interquartile range 15.6-123.4 months), and 60.8% male. The mortality rate was 10.5%. The prevalence of PICS-ped was 4.6%. Days using vasoactive drugs and days using antibiotics were associated with PICS-ped. PICS-ped was associated with mortality in crude (odds ratio = 6.67; P = 0.013) and adjusted analysis (odds ratio = 7.14; P = 0.017). PICS-ped was also associated with PICU and hospital length of stay, as well as duration of mechanical ventilation. Similar results were found in a subset of critically ill children who required mechanical ventilation for more than 48 h. CONCLUSIONS: Children with PICS-ped required antibiotics or vasoactive drugs for a longer period. PICS-ped was associated with poor clinical outcomes in critically ill children. More studies are needed to properly define PICS-ped for this population.

Relationship of arsenic and chromium availability with carbon functional groups, aluminum and iron in Little Washita River Experimental Watershed Reservoirs, Oklahoma, USA.

Sediment from three reservoirs located in the Little Washita River Experimental Watershed (LWREW) in Oklahoma, USA with contrasting dominant land uses were analyzed for total and extractable concentrations of arsenic (As) and chromium (Cr), and the potential ecologic risk to benthic organisms. Extractable As ranged from 0.24 to 1.21 mg kg-1, in the order grazing>cropland>forest and 0.13-0.58 mg kg-1 for extractable Cr, in the order of forest>grazing>cropland. However, only approximately < 1.5% of total As and < 4% of total Cr were extractable. Total As ranged from 16.2 to 141 mg kg-1 and total Cr ranged from 5.06 to 40.1 mg kg-1 both in the order of cropland>grazing>forest. The sediment exhibited an alkaline pH (8.0-8.7). As sorption exhibited a positive relationship with Al (r = 0.9995; P = 0.0001), Fe (r = 0.9829; P = 0.0001), and C (r = 0.4090; P = 0.0017) and Cr correlated positively with Al (r = 0.9676 P = 0.0001), Fe (r = 0.9818; P = 0.0001), and C (r = 0.3368; P = 0.0111). In addition, both As and Cr exhibited positive relationships with carbon (C) functional groups in the order of O-alkyl C> methoxyl C> alkyl C> aromatic C> carboxyl C> phenolic C. The sediment concentration analysis results illustrated that As in all reservoirs exceeded their respective Threshold Effect Level (TEL) and/or Probable Effect Level (PEL) indicating that existing concentrations of metals in these sediments were sufficiently high to cause adverse effects. However, Cr concentrations in all reservoirs evaluated was lower compared to the TEL and PEL.

Oral Kaposi sarcoma development is associated with HIV viral load, CD4+ count and CD4+/CD8+ ratio.

BACKGROUND: Kaposi's sarcoma (KS) is an uncommon, multifocal and angioproliferative lesion, which demonstrates a poor prognosis. The aim of the present research was to explore the association of HIV viral load, CD4+ and CD8+ counts and the CD4+/CD8+ ratio on the risk of oral Kaposi's sarcoma (KS) development. MATERIAL AND METHODS: A total of 62 patients were retrieved from March 2008 to October 2020 from the files of two oral pathology centres. Clinical, laboratory and follow-up data were retrieved from their medical files. Poisson regression was used to explore the role of history of immunosuppression and its association with oral KS development. A P-value <0.05 was considered significant. RESULTS: Sixty-two patients were included in the present study (32 with oral KS and 30 with no presentation of lesions anywhere on the body). Patients with oral KS presented a mean age of 32.6 years, and male patients were more affected. The hard palate (15 cases; 46.8%) was the main anatomical site affected. The lesions were mostly presented as swellings (13 cases; 40.6%) and nodules (12 cases; 37.5%). Systemic manifestations were also observed, including candidiasis (4 cases; 12.5%), bacterial infection (3 cases; 9.3%), tuberculosis (3 cases; 9.3%), herpes simplex (3 cases; 9.3%) and pneumonia (3 cases; 9.3%). A significant correlation was observed between HIV viral load, CD4+ count and the CD4+/CD8+ ratio with oral KS development. CONCLUSIONS: HIV viral load, CD4+ count and the CD4+/CD8+ ratio are associated with oral KS development.

On the use of Europium (Eu) for designing new metal-based anticancer drugs.

Europium oxide (Eu2O3) was used to evaluate the affinity of this rare earth element for interacting with double-stranded (ds) DNA molecules. To perform the study, we used single molecule force spectroscopy with optical tweezers and gel electrophoresis assays. Force spectroscopy experiments show that Eu2O3 presents a strong interaction with dsDNA, and the binding is independent on the ionic strength used in the surrounding environment. Among the main characteristics of the interaction, Eu2O3 tends to bind in a cooperative way, forming bound clusters of ∼ 3 molecules, and presents a high equilibrium association binding constant on the order of 105 M-1. In addition, gel electrophoresis confirm the weak electrostatic character of the interaction and explicit show that Eu2O3 does not interfere on drug intercalation into the double-helix. Such results demonstrate the potential of europium for interacting with nucleic acids and strongly suggest that this rare earth element may be considered for the design of new metal-based anticancer drugs in the future.