Brazilian dentist's knowledge of minimum intervention dentistry for caries management: application of a developed knowledge scale (MIDDeC-KS) and evaluation of its psychometric properties.

AIM: To assess the knowledge of Brazilian dentists about Minimum Intervention (MI) using a Minimum Intervention Dentistry to Dental Caries-Knowledge Scale (MIDDeC-KS) and evaluate its psychometric properties. MATERIALS AND METHODS: An online scale was developed to evaluate dentists' knowledge about MI. The higher the score, the greater the knowledge and vice versa. A preliminary study was carried out with 143 dentists to validate the MIDDeC-KS. For psychometric properties analysis, convergent and discriminant validity, test-retest reliability, and internal consistency of the instrument were assessed. After validation, MIDDeC-KS was applied to a representative sample of Brazilian dentists. T test for independent samples, Chi-square, and/or ANOVA one-way tests were applied. RESULTS: The MIDDeC-KS convergent (Spearman's = 0.48) and discriminant (P = 0.001) validity and reliability (ICC = 0.85, α = 0.72 and ω = 0.74) were proved. The participants (n = 637) obtained an overall mean score of 7.4 ± 2.5. The sample was mainly composed of females (P < 0.01), who graduated over 10 years prior (P = 0.02), from public colleges (P < 0.01), and most were pediatric dentists (38.2%). The highest and lowest scores were reached by pediatric dentists (9.2 ± 1.6) and bucomaxillofacial professionals (3.1 ± 2.1), respectively. Brazilian dentists demonstrated more knowledge about diet, biofilm, and topical fluoride control (84.3%), while the Hall technique (31.9%), resin infiltrant (47.6%), and chemical mechanical caries removal (48.4%) were the least known MI techniques. CONCLUSION: Brazilian dentists demonstrated more knowledge about preventive measures and less about more recent protocols, such as the Hall technique, resin infiltrant, and chemical mechanical caries tissue removal. Sufficient psychometric evidence of the MIDDeC-KS was found. CLINICAL RELEVANCE: Identify dentist's knowledge about MI.

Occurrence of bisphosphonate-associated osteonecrosis of the jaws in individuals with rheumatoid arthritis - a systematic review.

BACKGROUND: To access the occurrence of bisphosphonate-associated osteonecrosis of the jaw (BAONJ) in individuals with rheumatoid arthritis (RA). MATERIAL AND METHODS: Observational studies that evaluated the occurrence of BAONJ in individuals with RA (BAONJ-RA) were considered for inclusion. Electronic searches were performed up to December 2022 in six databases and in the grey literature. The study selection, data extraction, and quality assessment of the included studies according to the Joanna Briggs Institute Critical Appraisal Checklists was performed. The certainty of evidence was evaluated using the GRADE approach. RESULTS: Five studies were included three cohort and two cross-sectional. The sample size of subjects with RA ranged from 16 to 3201. Together, the studies presented 36 cases of BAONJ-RA. Prevalence of BAONJ-RA ranged from 0.094% to 56.25%. The incidence ranged from 0.4% to 2.21. Women between the 6th and 8th decade of life were the most affected. Alendronate (n=5) and zoledronic acid (n=9), orally and intravenously, respectively, were the most used bisphosphonates. The duration of bisphosphonates use ranged from 2.7 to 8 years. The certainty of evidence was very low. CONCLUSIONS: The occurrence of BAONJ-RA is low. However, the certainty of the evidence was very low for this outcome.

Current and new frontiers in hereditary cancer surveillance: Opportunities for liquid biopsy.

At least 5% of cancer diagnoses are attributed to a causal pathogenic or likely pathogenic germline genetic variant (hereditary cancer syndrome-HCS). These individuals are burdened with lifelong surveillance monitoring organs for a wide spectrum of cancers. This is associated with substantial uncertainty and anxiety in the time between screening tests and while the individuals are awaiting results. Cell-free DNA (cfDNA) sequencing has recently shown potential as a non-invasive strategy for monitoring cancer. There is an opportunity for high-yield cancer early detection in HCS. To assess clinical validity of cfDNA in individuals with HCS, representatives from eight genetics centers from across Canada founded the CHARM (cfDNA in Hereditary and High-Risk Malignancies) Consortium in 2017. In this perspective, we discuss operationalization of this consortium and early data emerging from the most common and well-characterized HCSs: hereditary breast and ovarian cancer, Lynch syndrome, Li-Fraumeni syndrome, and Neurofibromatosis type 1. We identify opportunities for the incorporation of cfDNA sequencing into surveillance protocols; these opportunities are backed by examples of earlier cancer detection efficacy in HCSs from the CHARM Consortium. We seek to establish a paradigm shift in early cancer surveillance in individuals with HCSs, away from highly centralized, regimented medical screening visits and toward more accessible, frequent, and proactive care for these high-risk individuals.

The Affective Dynamics of Everyday Digital Life: Opening Computational Possibility.

Up to now, there was no way to observe and track the affective impacts of the massive amount of complex visual stimuli that people encounter "in the wild" during their many hours of digital life. In this paper, we propose and illustrate how recent advances in AI-trained ensembles of deep neural networks-can be deployed on new data streams that are long sequences of screenshots of study participants' smartphones obtained unobtrusively during everyday life. We obtained affective valence and arousal ratings of hundreds of images drawn from existing picture repositories often used in psychological studies, and a new screenshot repository chronicling individuals' everyday digital life from both N = 832 adults and an affect computation model (Parry & Vuong, 2021). Results and analysis suggest that (a) our sample rates images similarly to other samples used in psychological studies, (b) the affect computation model is able to assign valence and arousal ratings similarly to humans, and (c) the resulting computational pipeline can be deployed at scale to obtain detailed maps of the affective space individuals travel through on their smartphones. Leveraging innovative methods for tracking the emotional content individuals encounter on their smartphones, we open the possibility for large-scale studies of how the affective dynamics of everyday digital life shape individuals' moment-to-moment experiences and well-being. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-023-00202-4.

Who's Accountable? Low-Value Care Received By Medicare Beneficiaries Outside Of Their Attributed Health Systems.

Policy makers and payers increasingly hold health systems accountable for spending and quality for their attributed beneficiaries. Low-value care-medical services that offer little or no benefit and have the potential for harm in specific clinical scenarios-received outside of these systems could threaten success on both fronts. Using national Medicare data for fee-for-service beneficiaries ages sixty-five and older and attributed to 595 US health systems, we describe where and from whom they received forty low-value services during 2017-18 and identify factors associated with out-of-system receipt. Forty-three percent of low-value services received by attributed beneficiaries originated from out-of-system clinicians: 38 percent from specialists, 4 percent from primary care physicians, and 1 percent from advanced practice clinicians. Recipients of low-value care were more likely to obtain that care out of system if age 75 or older (versus ages 65-74), male (versus female), non-Hispanic White (versus other races or ethnicities), rural dwelling (versus metropolitan dwelling), more medically complex, or experiencing lower continuity of care. However, out-of-system service receipt was not associated with recipients' health systems' accountable care organization status. Health systems might improve quality and reduce spending for their attributed beneficiaries by addressing out-of-system receipt of low-value care-for example, by improving continuity.

Immunoregulatory mechanisms between epithelial clear cells and mononuclear phagocytes in the epididymis.

INTRODUCTION: One of the most intriguing aspects of male reproductive physiology is the ability of the epididymis to prevent the mounting of immune responses against the onslaught of foreign antigens carried by spermatozoa while initiating very efficient immune responses versus stressors. Epithelial clear cells are strategically positioned to work in a concerted manner with region-specific heterogeneous subsets of mononuclear phagocytes to survey the epididymal barrier and regulate the balance between inflammation and immune tolerance in the post-testicular environment. OBJECTIVE: This review aims to describe how clear cells communicate with mononuclear phagocytes to contribute to the unique immune environment in which sperm mature and are stored in the epididymis. MATERIALS/METHODS: A comprehensive systematic review was performed. PubMed was searched for articles specific to clear cells, mononuclear phagocytes, and epididymis. Articles that did not specifically address the target material were excluded. RESULTS: In this review, we discuss the unexpected roles of clear cells, including the transfer of new proteins to spermatozoa via extracellular vesicles and nanotubes as they transit along the epididymal tubule; and we summarize the immune phenotype, morphology, and antigen capturing, processing, and presenting abilities of mononuclear phagocytes. Moreover, we present the current knowledge of immunoregulatory mechanisms by which clear cells and mononuclear phagocytes may contribute to the immune-privileged environment optimal for sperm maturation and storage. DISCUSSION AND CONCLUSION: Notably, we provide an in-depth characterization of clear cell-mononuclear phagocyte communication networks in the steady-state epididymis and in the presence of injury. This review highlights crucial concepts of mucosal immunology and cellcell interactions, all of which are critical but understudied facets of human male reproductive health.

Assessment of the reliability of YouTube™ videos about zirconia crowns in pediatric dentistry.

PURPOSE: To evaluate the reliability of YouTube™ videos on zirconia crowns in pediatric dentistry. METHODS: On January 4, 2022, a search was performed using the term "pediatric zirconia crown". The first 100 videos on the subject were included. Non-English videos, duplicates, and off-topic videos were excluded. For each video, an examiner recorded the number of views, likes, comments, channel followers, upload date, duration, and category rating. Two examiners assessed the reliability of the information presented in the videos using DISCERN, a brief questionnaire and scale score used to assess in a valid and reliable way the quality of information on treatment choices for health problems. Descriptive and inferential analyses were performed (p < 0.05). RESULTS: Of the initial 100 videos, 72 were excluded because of language, duplication, and subject matter. The 28 remaining videos had an average of 3.5 comments, 8,896.18 channel followers, 5,614.00 views, 19.14 likes, and a duration of 840.32 s. The average view rate was 7.54 per day ± 10,206.81. There was a statistically significant difference between the number of views and comments (p < 0.001), likes and comments (p < 0.001), and likes and views (p = 0.006). According to the DISCERN, none of the videos received the maximum grade to be considered very good. Two were considered good, nine fair, fourteen poor, and three very poor. CONCLUSION: Given that the majority of YouTube™ videos currently available on zirconia crowns in pediatric dentistry were deemed unreliable according to the DISCERN questionnaire, caution should be exercised when using the information presented.

Comparable cellular and humoral immunity upon homologous and heterologous COVID-19 vaccination regimens in kidney transplant recipients.

Background: Kidney transplant recipients (KTRs) are at high risk for a severe course of coronavirus disease 2019 (COVID-19); thus, effective vaccination is critical. However, the achievement of protective immunogenicity is hampered by immunosuppressive therapies. We assessed cellular and humoral immunity and breakthrough infection rates in KTRs vaccinated with homologous and heterologous COVID-19 vaccination regimens. Method: We performed a comparative in-depth analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T-cell responses using multiplex Fluorospot assays and SARS-CoV-2-specific neutralizing antibodies (NAbs) between three-times homologously (n = 18) and heterologously (n = 8) vaccinated KTRs. Results: We detected SARS-CoV-2-reactive T cells in 100% of KTRs upon third vaccination, with comparable frequencies, T-cell expression profiles, and relative interferon γ and interleukin 2 production per single cell between homologously and heterologously vaccinated KTRs. SARS-CoV-2-specific NAb positivity rates were significantly higher in heterologously (87.5%) compared to homologously vaccinated (50.0%) KTRs (P < 0.0001), whereas the magnitudes of NAb titers were comparable between both subcohorts after third vaccination. SARS-CoV-2 breakthrough infections occurred in equal numbers in homologously (38.9%) and heterologously (37.5%) vaccinated KTRs with mild-to-moderate courses of COVID-19. Conclusion: Our data support a more comprehensive assessment of not only humoral but also cellular SARS-CoV-2-specific immunity in KTRs to provide an in-depth understanding about the COVID-19 vaccine-induced immune response in a transplant setting.

Worldwide research trends on the use of chemical-mechanical caries removal products over the years: a critical review.

BACKGROUND: Chemical-mechanical caries removal (CMCR) products are in constant evolution and were recommended during the COVID-19 pandemic as substitutes for conventional caries removal. AIM: Characterize the worldwide scientific literature about CMCR products, over the years, by means of a critical review. DESIGN: Electronic search was performed on Medline/PubMed, Scopus, Web of Science, Cochrane Library, Lilacs, and Embase up to November 2020. Year, journal, country of authors, and type of study were the data extracted from the retrieved studies. Additional data of the clinical studies and systematic reviews were investigated. RESULTS: 2221 records were identified, 397 selected. 2011-2020 period concentrates higher number of publications (n = 169), in the Journal of Dental Research (n = 51), developed in Brazil (n = 45) and India (n = 44). Most studies were in vitro (n = 211) and clinical trials (n = 101). Carisolv™ (n = 48) and Papacarie Duo Gel™ (n = 33) were the most used products, prescript in isolated usage (n = 101), and compared with drills (n = 77). CMCR were more studied in primary teeth (n = 78), receiving glass ionomer cement (GIC) (n = 51) as restorative material. The most evaluated outcomes were time spent (n = 48) and pain (n = 41). Clinical application of CMCR takes more time than other techniques, but can also reduce patient anxiety, pain, and need for anesthesia. CONCLUSION: In vitro and clinical studies with CMCR products have been increasing, mostly carried out in developing countries, evaluating Carisolv™ and Papacarie Duo Gel™. Clinical studies tend to evaluate the time spent and pain compared to drills for removing caries in primary teeth, posteriorly restored with GIC. CMCR clinical application reduces anxiety, pain, and need for anesthesia, despite increase treatments' time.

Complete response to pembrolizumab in a patient with dermatomyositis and MMR deficient ovarian cancer: A case report.

•Immune checkpoint inhibitors can be safely administered to patients with dermatomyositis.•Immunosuppressants did not impact the efficacy of treatment with an immune check point inhibitor.•Patients with autoimmune disorders who require immune check point inhibitors should be monitored by a rheumatologist.

Psoralen mapping reveals a bacterial genome supercoiling landscape dominated by transcription.

DNA supercoiling is a key regulator of all DNA metabolic processes including replication, transcription, and recombination, yet a reliable genomic assay for supercoiling is lacking. Here, we present a robust and flexible method (Psora-seq) to measure whole-genome supercoiling at high resolution. Using this tool in Escherichia coli, we observe a supercoiling landscape that is well correlated to transcription. Supercoiling twin-domains generated by RNA polymerase complexes span 25 kb in each direction - an order of magnitude farther than previous measurements in any organism. Thus, ribosomal and many other highly expressed genes strongly affect the topology of about 40 neighboring genes each, creating highly integrated gene circuits. Genomic patterns of supercoiling revealed by Psora-seq could be aptly predicted from modeling based on gene expression levels alone, indicating that transcription is the major determinant of chromosome supercoiling. Large-scale supercoiling patterns were highly symmetrical between left and right chromosome arms (replichores), indicating that DNA replication also strongly influences supercoiling. Skew in the axis of symmetry from the natural ori-ter axis supports previous indications that the rightward replication fork is delayed several minutes after initiation. Implications of supercoiling on DNA replication and chromosome domain structure are discussed.

Tricyclic antidepressants target FKBP51 SUMOylation to restore glucocorticoid receptor activity.

FKBP51 is an important inhibitor of the glucocorticoid receptor (GR) signaling. High FKBP51 levels are associated to stress-related disorders, which are linked to GR resistance. SUMO conjugation to FKBP51 is necessary for FKBP51's inhibitory action on GR. The GR/FKBP51 pathway is target of antidepressant action. Thus we investigated if these drugs could inhibit FKBP51 SUMOylation and therefore restore GR activity. Screening cells using Ni2+ affinity and in vitro SUMOylation assays revealed that tricyclic antidepressants- particularly clomipramine- inhibited FKBP51 SUMOylation. Our data show that clomipramine binds to FKBP51 inhibiting its interaction with PIAS4 and therefore hindering its SUMOylation. The inhibition of FKBP51 SUMOylation decreased its binding to Hsp90 and GR facilitating FKBP52 recruitment, and enhancing GR activity. Reduction of PIAS4 expression in rat primary astrocytes impaired FKBP51 interaction with GR, while clomipramine could no longer exert its inhibitory action. This mechanism was verified in vivo in mice treated with clomipramine. These results describe the action of antidepressants as repressors of FKBP51 SUMOylation as a molecular switch for restoring GR sensitivity, thereby providing new potential routes of antidepressant intervention.

Does the addition of chlorhexidine to glass ionomer cements influence its antimicrobial effect and survival rate? A systematic review.

PURPOSE: To evaluate the influence of the addition of chlorhexidine on the antimicrobial effect and on the survival of restorations performed with glass ionomer cement. METHODS: Nine databases were used to search for randomized clinical trials that compared the survival rate and the antimicrobial effect of glass ionomer cement (GIC) restorations with and without the incorporation of chlorhexidine (CHX), without restrictions on year or language. Cochrane Collaboration's Risk of Bias 2 was used to assess the risk of bias. The GRADE approach was used to assess the certainty of evidence. RESULTS: From 593 studies found, seven met the inclusion criteria. The concentration of CHX varied between 0.5 and 2%. In general, the addition of CHX to GIC promoted reductions in Streptococcus mutans and Lactobacillus acidophilus burdens when compared to those without CHX. No study showed a difference in the survival of restorations between GIC with CHX and conventional GIC. Individual risk of bias varied from low to high and the certainty of evidence was classified as very low. CONCLUSIONS: Based on a very low level of certainty, the evidence suggests that the incorporation of CHX in GIC might improve the antimicrobial effects for a short time, in addition to having little influence on the survival of the restoration.

Worldwide trends on molar incisor and deciduous molar hypomineralisation research: a bibliometric analysis over a 19-year period.

AIM: To identify the worldwide trends in scientific evidence and gaps in knowledge regarding molar incisor hypomineralisation (MIH) and deciduous molar hypomineralisation/hypomineralised second primary molars (DMH/HSPM), exploring the contribution of authors and countries, possible etiological factors and proposed treatments, in order to guide future research in the area. METHODS: Searches were conducted in MEDLINE, Scopus, Web of Science, Cochrane Library, Lilacs/BBO, Embase and Google Scholar. Studies employing the terms MIH, DMH/HSPM and their linguistic variations were included. The following data were extracted: title, authors, year and journal of publication and first author's affiliation country. Studies were categorized according to topic, dentition, study design, etiological factors and types of treatments. Categories were analysed in relation to their distribution, co-occurrence, cross-correlation and/or autocorrelation. RESULTS: Five hundred and three studies were included. The most published authors were Manton D (n = 47), de Souza JF (n = 22) and Ghanim A (n = 22) and four main collaboration clusters have been identified. Most of the studies were conducted on permanent dentition (MIH) (87.4%); with observational design (57.2%). The "European Archives of Paediatric Dentistry" was the most published journal (13.3%) and a significant increase in the number of publications was observed in the last decade. MIH was most studied in relation to prevalence/incidence, systemic factors involved in its aetiology and treatment with composite restorations, while a gap in knowledge was observed for extraction and sealants. Less studies were published on DMH/HSPM and most of them evaluated risk factors or prevalence/incidence. The gap of knowledge was observed in relation to treatments and patient's quality of life. CONCLUSIONS: This bibliometric review provided a comprehensive overview of research in MIH and DMH/HSPM over the past 19 years. Within the limitations of the present study, the following conclusions can be drawn: global trends point to an increasing peak of scientific publication, especially in the last decade, while there is a shortage of clinical studies on treatments, mainly evaluating tooth extractions. Finally the multifactorial nature should be further explored, considering environmental and systemic factors together.

Treatment time, pain experience and acceptability of the technique for caries removal in primary teeth using the ART approach with or without Brix3000™ papain gel: a preliminary randomised controlled clinical trial.

PURPOSE: To compare the Atraumatic Restorative Treatment (ART) associated with Brix3000™ to ART considering treatment time, pain experienced, and acceptability to children. METHODS: This study was accepted in Research Ethics Committee in July 2019 (number 3469402). Healthy patients (n = 20) aged 3-9 years, with at least one primary molar with occlusal dentine caries without cusp involvement were randomly allocated to either the ART + Brix3000™ group or the ART-only group. The sample was characterised by sex, age, tooth location and caries experience. Time spent and pain experience scores were recorded at prophylaxis, caries removal and restoration. The pain experience (intense, moderate, or mild) was evaluated by the Face, Legs, Activity, Cry, Consolability-revised scale (FLACC-r). Acceptability was assessed by a five-point hedonic facial scale (dichotomised into 'like' and 'indifferent/dislike' bins) and by an open-question interview. Mann-Whitney, Chi-square, and Fisher's exact tests were applied to discern differences in time, pain/sample characterisation and acceptability, respectively. RESULTS: The ART + Brix3000™ group required 8.6 ± 3.1 min to remove caries tissue, whereas the ART group required only 4.8 ± 2.0 min (p = 0.03). The total time spent with treatments was 13.1 ± 4.0 min for ART + Brix3000™, and 9.8 ± 2.7 min for ART (p = 0.03). There was no difference in pain experience and acceptability found among the groups (p > 0.05). CONCLUSION: Although the ART + Brix3000™ technique demanded more treatment time than the ART alone, there were no differences in either pain experience or acceptability.

What are microbiological effects of the adjunctive use of probiotics in the treatment of periodontal diseases? A systematic review.

Probiotics have aroused great interest as an adjunctive treatment to periodontal therapy, due to the frequent colonisation by periodontopathogens after therapy. The aim of this systematic review was to analyse in the scientific literature, evidence of the microbiological effects of probiotics as an adjunct to periodontal therapy in the treatment of periodontal diseases (PD). Only randomised controlled trials (RCT), evaluating the microbiological effect of probiotics as an adjunct to periodontal therapy. The authors conducted a search in PubMed/MEDLINE, LILACS, ScienceDirect, Web of Science and Cochrane Library to identify articles published in English until February 2020. The quality of the studies was assessed using the JADAD scale and the risk of bias was assessed according to the Cochrane Collaboration assessment tool. Of the 265 articles potentially relevant to this review, 10 studies were included. The most frequently used probiotic bacteria were those of the genus Lactobacillus spp. and the time of administration of the probiotics was between 14 days to 3 months. Most studies have shown that the adjuvant use of probiotics reduces the total mean counts of gram-negative anaerobic species (Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola and Prevotella intermedia) and gram-negative coccobacillus (Aggregatibacter actinomycetemcomitans) of subgingival plaque samples. Probiotics adjuvant to periodontal therapy reduces periodontopathogenic species in a greater proportion, compared only to periodontal therapy. Especially the Lactobacillus reuteri strain, without combination with other strains, offered a greater reduction in pathogenic bacteria associated with greater destruction of periodontal tissues and deep periodontal pockets. Researchers should perform high-quality RCT, evaluating single strains without combinations, in order to observe the microbiological benefits as adjunctive treatment of PD.

US Ventilator Allocation and Patient Triage Policies in Anticipation of the COVID-19 Surge.

Before the predicted March 2020 surge of COVID-19, US healthcare organizations were charged with developing resource allocation policies. We assessed policy preparedness and substantive triage criteria within existing policies using a cross-sectional survey distributed to public health personnel and healthcare providers between March 23 and April 23, 2020. Personnel and providers from 68 organizations from 34 US states responded. While half of the organizations did not yet have formal allocation policies, all but 4 were in the process of developing policies. Using manual abstraction and natural language processing, we summarize the origins and features of the policies. Most policies included objective triage criteria, specified inapplicable criteria, separated triage and clinical decision making, detailed reassessment plans, offered an appeals process, and addressed palliative care. All but 1 policy referenced a sequential organ failure assessment score as a triage criterion, and 10 policies categorically excluded patients. Six policies were almost identical, tracing their origins to influenza planning. This sample of policies reflects organizational strategies of exemplar-based policy development and the use of objective criteria in triage decisions, either before or instead of clinical judgment, to support ethical distribution of resources. Future guidance is warranted on how to adapt policies across disease type, choose objective criteria, and specify processes that rely on clinical judgments.

Does a single application of contraceptive cause pathological changes in bitches? / [Uma única aplicação de anticoncepcional causa alterações patológicas em cadelas?]

O presente trabalho objetivou avaliar os efeitos da administração em dose única de progestágenos em fêmeas caninas hígidas, as quais nunca haviam recebido tais fármacos. Foram selecionadas 20 cadelas, que foram examinadas clinicamente e por meio de exames complementares. Nessas cadelas, foi aplicado medroxiprogesterona por via subcutânea. Noventa dias após, as fêmeas foram esterilizadas cirurgicamente, sendo os tecidos reprodutivos encaminhados para histopatologia. Foi possível verificar que, aos 30 dias, 12 animais (60%) apresentaram hiperplasia mamária. Aos 90 dias, 18 animais (90%) apresentavam sinais de hiperplasia endometrial cística, tendo cinco (27,77%) destes animais apresentado conteúdo purulento no lúmen uterino. No exame microscópico, apenas uma fêmea não demonstrou alterações patológicas, sendo a única que recebeu o contraceptivo na fase correta (anestro). As demais fêmeas apresentaram alterações que variaram entre alterações circulatórias a hiperplasia endometrial cística grave. Assim, foi possível concluir que uma única aplicação de anticoncepcional em fêmeas hígidas pode causar complicações leves a graves.(AU)

Optimized photochemistry enables efficient analysis of dynamic RNA structuromes and interactomes in genetic and infectious diseases.

Direct determination of RNA structures and interactions in living cells is critical for understanding their functions in normal physiology and disease states. Here, we present PARIS2, a dramatically improved method for RNA duplex determination in vivo with >4000-fold higher efficiency than previous methods. PARIS2 captures ribosome binding sites on mRNAs, reporting translation status on a transcriptome scale. Applying PARIS2 to the U8 snoRNA mutated in the neurological disorder LCC, we discover a network of dynamic RNA structures and interactions which are destabilized by patient mutations. We report the first whole genome structure of enterovirus D68, an RNA virus that causes polio-like symptoms, revealing highly dynamic conformations altered by antiviral drugs and different pathogenic strains. We also discover a replication-associated asymmetry on the (+) and (-) strands of the viral genome. This study establishes a powerful technology for efficient interrogation of the RNA structurome and interactome in human diseases.

When rice gets the chills: comparative transcriptome profiling at germination shows WRKY transcription factor responses.

Rice is vital for food security. Due to its tropical origin, rice suffers from cold temperatures that affect its entire life cycle. Key genes have been identified involved in cold tolerance. WRKYs are generally downstream of the MAPK cascade and can act together with VQ proteins to regulate stress-responsive genes. Chilling treatment was applied at germination to two rice genotypes (tolerant and sensitive). Shoots at S3 stage were collected for RNA-seq to identify OsWRKY, OsMAPKs and OsVQs expression. Relationships among MAPKs, WRKYs and VQs were predicted through correlation analysis. OsWRKY transcriptional regulation was predicted by in silico analysis of cis-regulatory elements. A total of 39 OsWRKYs were differentially expressed. OsWRKY21, OsWRK24 and OsWRKY69 are potential positive regulators, while OsWRKY10, OsWRK47, OsWRKY62, OsWRKY72 and OsWRKY77 are potential negative regulators, of chilling tolerance. 12 OsMAPKs were differentially expressed. OsMAPKs were downregulated and negatively correlated with the upregulated OsWRKYs in the tolerant genotype. 19 OsVQs were differentially expressed, three and six OsVQs were positively correlated with OsWRKYs in the tolerant and sensitive genotypes, respectively. Seven differentially expressed OsWRKYs have cold-responsive elements in their promoters and five upregulated OsWRKYs in the tolerant genotype contained the W-box motif. Chilling causes changes in OsWRKY, OsMAPK and OsVQ gene expression at germination. OsWRKYs may not act downstream of the MAPK cascade to coordinate chilling tolerance, but OsWRKYs may act with VQs to regulate chilling tolerance. Candidate OsWRKYs are correlated and have a W-box in the promoter, suggesting an auto-regulation mechanism.