DDX60 selectively reduces translation off viral type II internal ribosome entry sites.

Co-opting host cell protein synthesis is a hallmark of many virus infections. In response, certain host defense proteins limit mRNA translation globally, albeit at the cost of the host cell's own protein synthesis. Here, we describe an interferon-stimulated helicase, DDX60, that decreases translation from viral internal ribosome entry sites (IRESs). DDX60 acts selectively on type II IRESs of encephalomyocarditis virus (EMCV) and foot and mouth disease virus (FMDV), but not by other IRES types or by 5' cap. Correspondingly, DDX60 reduces EMCV and FMDV (type II IRES) replication, but not that of poliovirus or bovine enterovirus 1 (BEV-1; type I IRES). Furthermore, replacing the IRES of poliovirus with a type II IRES is sufficient for DDX60 to inhibit viral replication. Finally, DDX60 selectively modulates the amount of translating ribosomes on viral and in vitro transcribed type II IRES mRNAs, but not 5' capped mRNA. Our study identifies a novel facet in the repertoire of interferon-stimulated effector genes, the selective downregulation of translation from viral type II IRES elements.

Chemical reversion of age-related oocyte dysfunction fails to enhance embryo development in a bovine model of postovulatory aging.

PURPOSE: There are no clinical treatments to prevent/revert age-related alterations associated with oocyte competence decline in the context of advanced maternal age. Those alterations have been attributed to oxidative stress and mitochondrial dysfunction. Our study aimed to test the hypothesis that in vitro maturation (IVM) medium supplementation with antioxidants (resveratrol or phloretin) may revert age-related oocyte competence decline. METHODS: Bovine immature oocytes were matured in vitro for 23 h (young) and 30 h (aged). Postovulatory aged oocytes (control group) and embryos obtained after fertilization were examined and compared with oocytes supplemented with either 2 µM of resveratrol or 6 µM phloretin (treatment groups) during IVM. RESULTS: Aged oocytes had a significantly lower mitochondrial mass and proportion of mitochondrial clustered pattern, lower ooplasmic volume, higher ROS, lower sirtuin-1 protein level, and a lower blastocyst rate in comparison to young oocytes, indicating that postovulatory oocytes have a lower quality and developmental competence, thus validating our experimental model. Supplementation of IVM medium with antioxidants prevented the generation of ROS and restored the active mitochondrial mass and pattern characteristic of younger oocytes. Moreover, sirtuin-1 protein levels were also restored but only following incubation with resveratrol. Despite these findings, the blastocyst rate of treatment groups was not significantly different from the control group, indicating that resveratrol and phloretin could not restore the oocyte competence of postovulatory aged oocytes. CONCLUSION: Resveratrol and phloretin can both revert the age-related oxidative stress and mitochondrial dysfunction during postovulatory aging but were insufficient to enhance embryo developmental rates under our experimental conditions.

Understanding Interface Exchanges for Assessing Environmental Sorption of Additives from Microplastics: Current Knowledge and Perspectives.

Although the impacts of plastic pollution have long been recognized, the presence, pervasiveness, and ecotoxicological consequences of microplastic-i.e., plastic particles < 5 mm-contamination have only been explored over the last decade. Far less focus has been attributed to the role of these materials and, particularly, microplastics, as vectors for a multitude of chemicals, including those (un)intentionally added to plastic products, but also organic pollutants already present in the environment. Owing to the ubiquitous presence of microplastics in all environmental matrices and to the diverse nature of their chemical and physical characteristics, thoroughly understanding the mechanistic uptake/release of these compounds is inherently complex, but necessary in order to better assess the potential impacts of both microplastics and associated chemicals on the environment. Herein, we delve into the known processes and factors affecting these mechanisms. We center the discussion on microplastics and discuss some of the most prominent ecological implications of the sorption of this multitude of chemicals. Moreover, the key limitations of the currently available literature are described and a prospective outlook for the future research on the topic is presented.

Ketamine subcutaneous continuous infusion for depressive symptoms at home: A case report beyond pain use.

OBJECTIVES: Ketamine has been widely used in refractory pain as an opioid adjuvant. Evidence suggests that ketamine can also have an essential role in easing depressive symptoms. Its rapid onset of action makes it a valuable choice in palliative care. METHODS: We present a case of a 70-year-old man with stage IV renal carcinoma and bone metastasis. The main symptoms included neuropathic pain, depression, and a persistent and severe desire for death. RESULTS: We started continuous subcutaneous infusion with morphine 30 mg and ketamine 100 mg/day. The dose of ketamine was incremented to the maximum of 250 mg/day. During the 28-day treatment, we observed an overall improvement in neuropathic pain, depressive symptoms, and other end-of-life psychological aspects of distress. Only minor psychological side effects were identified, which were controlled by using midazolam in the continuous subcutaneous infusion. SIGNIFICANCE OF RESULTS: Some studies have already demonstrated the benefits of ketamine use in alleviating depression, using parental infusion or oral formulas, which are administered in hospice care. Our report enhances the benefit of the subcutaneous route for palliative patients cared for at home.

[How to improve community engagement in health: Analysis of proposed actions following the implementation of a community engagement assessment tool]. / ¿Cómo mejoramos la participación comunitaria en salud? Análisis de las acciones propuestas tras la aplicación de una herramienta de evaluación.

OBJECTIVE: To analyse the lines of action identified in the health promotion projects participating in the EvaluA GPS research, and their relationship with the scores assigned in EvalGuia, a tool for evaluating evidence-based community participation. DESIGN: Qualitative-quantitative multicentre study. SETTING: Primary care or intersectoral network of primary care and municipalities in five autonomous communities in Spain. PARTICIPANTS: Participants of 10 health promotion projects, selected with convenience sampling, following inclusion criteria (projects with a minimum of community engagement and centred on community health). METHOD: Data were collected through questionnaires (EvalGuía tool) and participatory workshops. Quantitative data were analysed with descriptive statistics, qualitative data were analysed using matrix analysis. RESULTS: After implementing the EvalGuide tool, the lowest scores were assigned in outcome evaluation, knowledge of policies related to community participation, diversity in the core working group, inclusivity policies, financial resources and diffusion of results. The lines of action proposed were heterogeneous and did not always match with those prioritised as lower score. The prioritised lines revolved around project organisation and communication. CONCLUSIONS: The EvalGuide tool can be helpful to design action plans in Health Promotion projects. The implementation of measures in 12 months to increase the diversity of the core working group, to incorporate work-life balance measures or to improve evaluation is difficult. More time is needed to implement such measures.

Reef Location and Client Diversity Influence the Skin Microbiome of the Caribbean Cleaner Goby Elacatinus evelynae.

Fish-associated microorganisms are known to be affected by the environment and other external factors, such as microbial transfer between interacting partners. One of the most iconic mutualistic interactions on coral reefs is the cleaning interactions between cleaner fishes and their clients, during which direct physical contact occurs. Here, we characterized the skin bacteria of the Caribbean cleaner sharknose goby, Elacatinus evelynae, in four coral reefs of the US Virgin Islands using sequencing of the V4 region of the 16S rRNA gene. We specifically tested the relationship between gobies' level of interaction with clients and skin microbiota diversity and composition. Our results showed differences in microbial alpha- and beta-diversity in the skin of gobies from different reef habitats and high inter-individual variation in microbiota diversity and structure. Overall, the results showed that fish-to-fish direct contact and specifically, access to a diverse clientele, influences the bacterial diversity and structure of cleaner gobies' skin. Because of their frequent contact with clients, and therefore, high potential for microbial exchange, cleaner fish may serve as models in future studies aiming to understand the role of social microbial transfer in reef fish communities.

Chronic health conditions and school experience in school-aged children in 19 European countries.

This study investigates chronic conditions (CC) prevalence among children in mainstream schools, their school experience and life satisfaction in Europe. Data were collected from the 2017/2018 HBSC survey, a cross-national study using self-reported questionnaires administered in classrooms. Nationally representative samples of children aged 11, 13, and 15 years in mainstream schools from 19 European countries (n = 104,812) were used. School experience was assessed using four variables: low school satisfaction, schoolwork pressure, low teacher support, and peer-victimization, which were related to life satisfaction. Latent class analysis (LCA) was conducted to identify patterns of school experience among students with CC. The prevalence of CC varied from 8.4 (Armenia) to 28.2% (Finland). Children with CC (n = 17,514) rated their school experience and life satisfaction lower than children without CC. LCA identified three school experience patterns: "negative on all items" (37%), "negative on all items, except school pressure" (40%) and "overall positive" (23%). The distribution of subgroups varied across countries-in countries with a higher proportion of children with CC in mainstream schools, children reported more negative school experiences. Compared to the "overall positive" group, low life satisfaction was highest for students classified as "negative on all items" (relative risk (RR) = 2.9; 95% CI 2.2-3.8) with a lesser effect for "negative on all items, except school pressure" (RR) = 1.8; 95% CI 1.4-2.4). These findings provide cross-national data documenting the diversity in inclusive educational practices regarding school placement and school experiences, and suggest that efforts are still needed to allow a fully inclusive environment.

Reuse of lime sludge from immediate one-step lime precipitation process as a coagulant (aid) in slaughterhouse wastewater treatment.

The circularity of wastewater treatment subproducts is on the worldwide agenda. In this way, this work aims to evaluate alternatives for the reuse of sludge from slaughterhouse wastewater treatment. Wetted sludges produced in the immediate one-step lime precipitation process were applied directly or first calcined, as a coagulant or coagulant aid, in the absence or presence of Ca(OH)2, to slaughterhouse wastewaters with different characteristics. For the best sludge reuse, successive reuses of the sludge were carried out and the characteristics of treated slaughterhouse wastewater were evaluated after each reuse. Results showed a great similarity between slaughterhouse and treated slaughterhouse wastewaters using wetted and calcined sludges as a coagulant for highly contaminated slaughterhouse wastewater. In addition, a great similarity was also observed between the calcined and the wetted sludges, both as a coagulant aid, for all the slaughterhouse wastewaters tested. However, the latter consumed more hydrated lime, more volume of sludge sedimented, and higher concentrations phosphorus and organic matter in the treated wastewater. Calcined sludge as a coagulant aid guaranteed the best slaughterhouse wastewater quality for almost of the tested paramenters (≥94% for absorbances at 254 nm and 410 nm, E. coli, turbidity, and phosphorus, chemical oxygen demand between 3 and 91%, and total Kjeldahl nitrogen between 3 and 62%) independently of the wastewater characteristics. Calcined sludge as a coagulant aid can be three times reused for the tested parameters and slaughterhouse wastewater characteristics without significantly decreasing the quality. The successive sludge reused saves the hydrated lime dose applied (up to 28.4%) and the sedimented sludge volume (up to 24.7%), and can be a solution to stabilize sludge due to the pH increase (sludge pH = 12).

Dissecting distinct proteolytic activities of FMDV Lpro implicates cleavage and degradation of RLR signaling proteins, not its deISGylase/DUB activity, in type I interferon suppression.

The type I interferon response is an important innate antiviral pathway. Recognition of viral RNA by RIG-I-like receptors (RLRs) activates a signaling cascade that leads to type I interferon (IFN-α/ß) gene transcription. Multiple proteins in this signaling pathway (e.g. RIG-I, MDA5, MAVS, TBK1, IRF3) are regulated by (de)ubiquitination events. Most viruses have evolved mechanisms to counter this antiviral response. The leader protease (Lpro) of foot-and-mouth-disease virus (FMDV) has been recognized to reduce IFN-α/ß gene transcription; however, the exact mechanism is unknown. The proteolytic activity of Lpro is vital for releasing itself from the viral polyprotein and for cleaving and degrading specific host cell proteins, such as eIF4G and NF-κB. In addition, Lpro has been demonstrated to have deubiquitination/deISGylation activity. Lpro's deubiquitination/deISGylation activity and the cleavage/degradation of signaling proteins have both been postulated to be important for reduced IFN-α/ß gene transcription. Here, we demonstrate that TBK1, the kinase that phosphorylates and activates the transcription factor IRF3, is cleaved by Lpro in FMDV-infected cells as well as in cells infected with a recombinant EMCV expressing Lpro. In vitro cleavage experiments revealed that Lpro cleaves TBK1 at residues 692-694. We also observed cleavage of MAVS in HeLa cells infected with EMCV-Lpro, but only observed decreasing levels of MAVS in FMDV-infected porcine LFPK αVß6 cells. We set out to dissect Lpro's ability to cleave RLR signaling proteins from its deubiquitination/deISGylation activity to determine their relative contributions to the reduction of IFN-α/ß gene transcription. The introduction of specific mutations, of which several were based on the recently published structure of Lpro in complex with ISG15, allowed us to identify specific amino acid substitutions that separate the different proteolytic activities of Lpro. Characterization of the effects of these mutations revealed that Lpro's ability to cleave RLR signaling proteins but not its deubiquitination/deISGylation activity correlates with the reduced IFN-ß gene transcription.

Protein intake and muscle mass maintenance in patients with cancer types with high prevalence of sarcopenia: a systematic review.

RATIONALE: Cancer is associated with muscle wasting. However, optimal protein intake has not been determined, limiting the efficacy of nutritional interventions. This systematic review aims to assess the effect of protein intake on muscle mass of patients with cancer types with high prevalence of sarcopenia during treatment, in longitudinal studies. METHODS: MEDLINE, CINAHL, and Scopus databases were searched following PRISMA guidelines. Longitudinal studies written in English, including adults with high sarcopenia prevalence cancer diagnosis, submitted to (chemo)radiotherapy, with assessment of protein intake and muscle changes during treatment, published until 4 October 2020 were included. Studies including supplementation with substances, such as n-3 fatty acids, specific amino acids, or proteins, were excluded. Study appraisal was independently conducted by two reviewers, and a qualitative research synthesis was performed. RESULTS: Overall, 575 records were identified, of which, eight studies were included (one randomized clinical trial and seven uncontrolled before and after studies). Patients with head and neck (n = 5), lung (n = 2), and esophageal cancer (n = 1) were included, comprising a total of 554 participants. The studies presented heterogeneous methodologies, objectives, and methods to assess body composition. Overall, participant groups with a mean protein intake below 1.2 g/kg presented muscle wasting, with one exception, while those reporting a mean intake above 1.4 g/kg, maintained muscle during treatment. CONCLUSIONS: Our findings show that protein intakes below 1.2 g/kg, even when within the recommendations, have been associated with muscle wasting during treatment. Only intakes above 1.4 g/kg have been associated with muscle maintenance. High-quality research is needed to establish an optimal dose response.

Two-year follow-up of children with congenital Zika syndrome: the evolution of clinical patterns.

The aim of the study was to describe neurological manifestations in children with congenital Zika syndrome (CZS) in the first 2 years of age. In this prospective observational study, children with CZS treated at a university hospital received a neurological assessment and were evaluated using two neurodevelopmental scales (the Denver II test and the assessment of gross motor development of the World Health Organization) by a pediatric neurologist on admission to the study and at 4, 8, 12, 18, and 24 months of age. The data collected were stored in Microsoft Excel version 14.6.3. Thirty-eight children (27 males and 11 females; a median age of 4.3 months (interquartile range (IQR): 1.6-11.4)) with CZS were evaluated. Irritability was present in 50% and 27% of the children at 8 months and 24 months, respectively. Axial hypertonia was highly prevalent at 4 months (77%), with a decrease to 50% at 24 months. At all ages, spastic tetraparesis was the most common motor abnormality (> 80%). Twenty-seven (71%) participants were diagnosed with epilepsy, and the median age at seizure onset was 6 months (IQR: 3.5-8). The most frequent types of seizures were focal seizures and spasms, with spasms being the most frequent in the first year of life (52%) and focal crises being the most frequent in the second year of life (50%).Conclusion: This study allowed observation of neurological abnormalities over time, the evolution of epileptic manifestations, and recognition of new patterns of clinical neurological abnormalities, helping clinicians to recognize CZS earlier, minimizing the impact of new outbreaks. What is Known: • Clinical patterns of SZC patients at pre-established ages or date of data collection • More frequent studies with data collection of clinical-radiological features of patient's over his first year of life What is New: • Comprehensive clinical neurological progression data regarding CZS in the first 2 years of life, recognizing patterns • Hypothesis including a new CZS spectrum with milder clinical-radiological features.

Efficacy of different neoadjuvant treatment regimens in BRCA-mutated triple negative breast cancer: a systematic review and meta-analysis.

PURPOSE: Triple negative breast cancer (TNBC) is an aggressive breast cancer strongly associated with BRCA mutation. Standard neoadjuvant chemotherapy remains the standard of care for early stage TNBC, the optimal chemotherapy regimen is still a matter of discussion. Other agents, such as poly-ADP-ribosyl polymerase inhibitors (PARPi) and anti-vascular endothelial growth factor (VEGF) antibodies were evaluated in the neoadjuvant setting. This systematic review and meta-analysis intend to evaluate the impact of neoadjuvant treatments in pCR rates in TNBC gBRCA mutation, beyond traditional standard chemotherapy. METHODS: PubMed, Clinicaltrials.gov, Cochrane CENTRAL, Embase and key oncological meetings for trials were searched for studies reporting neoadjuvant chemo-immunotherapy in BRCA positive TNBC. RESULTS: Out of 1238 records reviewed, thirty-one trials were included, resulting in a total 619 BRCA-mutated TNBC patients. In BRCA mutated TNBC patients who received cisplatin in monotherapy the proportion of patients who achieved pCR was 0.53 (95%CI [0.30, 0.76]), and when treatment combined standard chemotherapy and platin derivatives the proportion of pCR increased to 0.62 (95% CI [0.48, 0.76]). The group of patients treated with platin derivatives, anthracyclines ± taxanes achieved the highest proportion of pCR, 0.66. Patients treated with PARPi alone show a pCR proportion of 0.55 (95% CI [0.30, 0.81]); and when standard chemotherapy and platin derivatives were combined with PARPi the proportion of pCR did not vary. CONCLUSIONS: Patients with BRCA mutated TNBC treated with cisplatin in monotherapy demonstrate inferior proportion in the pCR achievement when compared with standard chemotherapy plus platin derivates. The best pCR was achieved with platin derivates in association with anthracyclines ± taxanes. No difference in pCR was found between PARPi alone vs PARPi with standard chemotherapy.

NSAID-Based Coordination Compounds for Biomedical Applications: Recent Advances and Developments.

After the serendipitous discovery of cisplatin, a platinum-based drug with chemotherapeutic effects, an incredible amount of research in the area of coordination chemistry has been produced. Other transition metal compounds were studied, and several new relevant metallodrugs have been synthetized in the past few years. This review is focused on coordination compounds with first-row transition metals, namely, copper, cobalt, nickel or manganese, or with zinc, which have potential or effective pharmacological properties. It is known that metal complexes, once bound to organic drugs, can enhance the drugs' biological activities, such as anticancer, antimicrobial or anti-inflammatory ones. NSAIDs are a class of compounds with anti-inflammatory properties used to treat pain or fever. NSAIDs' properties can be strongly improved when included in complexes using their compositional N and O donor atoms, which facilitate their coordination to metal ions. This review focuses on the research on this topic and on the promising or effective results that complexes of first-row transition metals and NSAIDs can exhibit.

Impairment of the DeISGylation Activity of Foot-and-Mouth Disease Virus Lpro Causes Attenuation In Vitro and In Vivo.

Foot-and-mouth disease virus (FMDV) leader proteinase (Lpro) affects several pathways of the host innate immune response. Previous studies in bovine cells demonstrated that deletions (leaderless [LLV]) or point mutations in Lpro result in increased expression of interferon (IFN) and IFN-stimulated genes (ISGs), including, among others, the ubiquitin-like protein modifier ISG15 and the ubiquitin specific peptidase USP18. In addition to its conventional papain-like protease activity, Lpro acts as a deubiquitinase (DUB) and deISGylase. In this study, we identified a conserved residue in Lpro that is involved in its interaction with ISG15. Mutation W105A rendered Escherichia coli-expressed Lpro unable to cleave the synthetic substrate pro-ISG15 while preserving cellular eIF4G cleavage. Interestingly, mutant FMDV W105A was viable. Overexpression of ISG15 and the ISGylation machinery in porcine cells resulted in moderate inhibition of FMDV replication, along with a decrease of the overall state of ISGylation in wild-type (WT)-infected cells. In contrast, reduced deISGylation was observed upon infection with W105A and leaderless virus. Reduction in the levels of deubiquitination was also observed in cells infected with the FMDV LproW105A mutant. Surprisingly, similarly to WT, infection with W105A inhibited IFN/ISG expression despite displaying an attenuated phenotype in vivo in mice. Altogether, our studies indicate that abolishing/reducing the deISGylase/DUB activity of Lpro causes viral attenuation independently of its ability to block the expression of IFN and ISG mRNA. Furthermore, our studies highlight the potential of ISG15 to be developed as a novel biotherapeutic molecule against FMD.IMPORTANCE In this study, we identified an aromatic hydrophobic residue in foot-and-mouth disease virus (FMDV) leader proteinase (Lpro) (W105) that is involved in the interaction with ISG15. Mutation in Lpro W105 (A12-LproW105A) resulted in reduced deISGylation in vitro and in porcine-infected cells. Impaired deISGylase activity correlated with viral attenuation in vitro and in vivo and did not affect the ability of Lpro to block expression of type I interferon (IFN) and other IFN-stimulated genes. Moreover, overexpression of ISG15 resulted in the reduction of FMDV viral titers. Thus, our study highlights the potential use of Lpro mutants with modified deISGylase activity for development of live attenuated vaccine candidates, and ISG15 as a novel biotherapeutic against FMD.

Does supplementation with mitochondria improve oocyte competence? A systematic review.

Mitochondrial supplementation was proposed as a complementary treatment to assisted reproductive technologies to improve oocyte competence and support post-fertilization development. This strategy is based on the fact that poor-quality/aged oocytes contain lower and dysfunctional mitochondria. However, the efficacy and safety of mitochondrial supplementation are still controversial. Therefore, this review summarizes the clinical/biological outcomes of mitochondrial supplementation, aiming to improve oocyte competence or explore the safety of this technique, and was based on an online search using PubMed and Web of Science, until September 2019. The studies included reported outcomes related to the efficacy and safety of mitochondrial supplementation either in human or animal models (bovine, porcine and mouse). Extracted data were organized according to study objective, the mitochondrial source and the main outcomes: fertilization/pregnancy rates, embryo development and adverse outcomes. Clinical pregnancy was not improved in the only randomized controlled trial published, although an increase was demonstrated in other non-randomized studies. Fertilization rate and embryo development were not different from control groups in the majority of studies, although performed in different contexts and using diverse sources of mitochondria. The safety of mitochondria transfer is still a concern, however, the euploid rate and the absence of reported congenital malformation from the clinical studies are reassuring. In summary, mitochondrial supplementation does not seem to cause harm although the benefit of improving oocyte competence is still unclear due to the diversity of methodological approaches and low-quality of the data available. Analyzed data support the need to investigate further, in both pre-clinical and clinical contexts.

Microsatellite markers for the endangered franciscana dolphin (Pontoporia blainvillei).

The franciscana (Pontoporia blainvillei) is the most threatened small cetacean in the South Atlantic. In this study we report the development of 13 microsatellite markers for franciscanas through next-generation sequencing, and the characterization of those loci in 38 samples from the species' northernmost population (Espírito Santo, Brazil). Besides providing diversity indices for the new, specific loci, we also report on the transferability of heterologous loci which had not been screened in franciscanas before, and review all loci used in previous studies. Expected heterozygosity in the new loci ranged between 0.107 and 0.595, and all but one were in Hardy Weinberg Equilibrium. These are the first microsatellite loci isolated from franciscanas, and they are an important addition to heterologous markers that were available previously.

Oral leukoplakia, leukoerythroplakia, erythroplakia and actinic cheilitis: Analysis of 953 patients focusing on oral epithelial dysplasia.

BACKGROUND: To analyse the clinical and histological characteristics from a series of oral leukoplakias, leukoerythroplakias, erythroplakias and actinic cheilitis diagnosed in a 14-year period. METHODS: The files were reviewed and all cases diagnosed as leukoplakia, leukoerythroplakia, erythroplakia and actinic cheilitis were selected. Clinical information was obtained from the biopsy submission forms, and histological review was performed in all cases. RESULTS: Final sample included 953 lesions, mostly affecting females (534, 56%), and 87.5% of the patients were 41 to 80 years old. The most commonly affected regions were the lower lip (20.1%), tongue (18.1%) and buccal mucosa (16.9%). Leukoplakias, actinic cheilitis, leukoerythroplakias and erythroplakias represented, respectively, 74.6%, 15.2%, 9.3% and 0.8% of the sample. Most cases presented no dysplasia (42.1%) or mild dysplasia (33.5%). Lesions in the tongue, floor of mouth and lower lip, as well as lesions that presented hyperparakeratosis, showed higher frequencies of moderate dysplasia and severe dysplasia/carcinoma in situ. The most common histological criteria were the increase in number and size of nucleoli, loss of polarity of the basal cells and variations in cellular size and shape. Classification by the binary system showed that 7% were high-risk lesions. CONCLUSION: All histological criteria for classification of oral epithelial dysplasia recommended by the World Health Organization showed increased frequency as grading increased. Additional criteria seem to be useful in grading oral epithelial dysplasia, such as the presence of normal and abnormal superficial mitotic figures and endophytic epithelial proliferation.

Fertility preservation in ovarian cancer patients.

Ovarian cancer is more frequent in post-menopausal women, however it can also occur in young premenopausal women. After diagnosis and cancer staging, health care providers should address the possibility of infertility and might offer fertility preservation options. Chemotherapy, frequently used when treating ovarian cancer, has proven to cause extensive ovarian damage. Standard surgery may be aggressive and the recurrence risk may not be relevant enough to opt for these approaches. Fertility sparing surgery has been progressively accepted and many alternative surgical approaches have proven to be successful in both cancer treatment, fertility preservation and low recurrence rates. Though there are several techniques available for fertility preservation in cancer patients, when dealing with ovarian cancer patients, oocyte and embryo cryopreservation are the only suitable. Ovarian tissue cryopreservation has been largely studied, but no data on ovarian cancer patients exist, due to the risk of reimplanting cancer cells.

Mek1 coordinates meiotic progression with DNA break repair by directly phosphorylating and inhibiting the yeast pachytene exit regulator Ndt80.

Meiotic recombination plays a critical role in sexual reproduction by creating crossovers between homologous chromosomes. These crossovers, along with sister chromatid cohesion, connect homologs to enable proper segregation at Meiosis I. Recombination is initiated by programmed double strand breaks (DSBs) at particular regions of the genome. The meiotic recombination checkpoint uses meiosis-specific modifications to the DSB-induced DNA damage response to provide time to convert these breaks into interhomolog crossovers by delaying entry into Meiosis I until the DSBs have been repaired. The meiosis-specific kinase, Mek1, is a key regulator of meiotic recombination pathway choice, as well as being required for the meiotic recombination checkpoint. The major target of this checkpoint is the meiosis-specific transcription factor, Ndt80, which is essential to express genes necessary for completion of recombination and meiotic progression. The molecular mechanism by which cells monitor meiotic DSB repair to allow entry into Meiosis I with unbroken chromosomes was unknown. Using genetic and biochemical approaches, this work demonstrates that in the presence of DSBs, activated Mek1 binds to Ndt80 and phosphorylates the transcription factor, thus inhibiting DNA binding and preventing Ndt80's function as a transcriptional activator. Repair of DSBs by recombination reduces Mek1 activity, resulting in removal of the inhibitory Mek1 phosphates. Phosphorylation of Ndt80 by the meiosis-specific kinase, Ime2, then results in fully activated Ndt80. Ndt80 upregulates transcription of its own gene, as well as target genes, resulting in prophase exit and progression through meiosis.

An urgent call to think globally and act locally on landfill disposable plastics under and after covid-19 pandemic: Pollution prevention and technological (Bio) remediation solutions.

Landfilling and illegal waste disposal have risen to deal with the COVID-19 potentially infectious waste, particularly in developing countries, which aggravates plastic pollution and inherent environmental threats to human and animal health. It is estimated that 3.5 million metric tonnes of masks (equivalent to 601 TIR containers) have been landfilled worldwide in the first year, with the potential to increase global plastic municipal solid waste by 3.5%, alter biogas composition, and release 2.3 × 1021 microplastics to leachates or adjacent environments, in the coming years. This paper reviews the challenges raised in the pandemic scenario on landfills and discusses the potential environmental and health implications that might drive us apart from the 2030 U.N. sustainable goals. Also, it highlights some innovative technologies to improve waste management (from collection to disposal, waste reduction, sterilization) and mitigates plastic leakage (emission control approaches, application of biotechnological and monitoring/computational tools) that can pave the way to environmental recovery. COVID-19 will eventually subside, but if no action is taken in the short-term towards effective plastic policies, replacement of plastics for sustainable alternatives (e.g., biobased plastics), improvement of waste management streams (prioritising flexible and decentralized approaches), and a greater awareness and responsibility of the general public, stakeholders, industries; we will soon reach a tipping-point in natural environments worldwide.