Structural and functional characterization of genes PYL-PP2C-SnRK2s in the ABA signalling pathway of Cucurbita pepo.

BACKGROUND: The core regulation of the abscisic acid (ABA) signalling pathway comprises the multigenic families PYL, PP2C, and SnRK2. In this work, we conducted a genome-wide study of the components of these families in Cucurbita pepo. RESULTS: The bioinformatic analysis of the C. pepo genome resulted in the identification of 19 CpPYL, 102 CpPP2C and 10 CpSnRK2 genes. The investigation of gene structure and protein motifs allowed to define 4 PYL, 13 PP2C and 3 SnRK2 subfamilies. RNA-seq analysis was used to determine the expression of these gene families in different plant organs, as well as to detect their differential gene expression during germination, and in response to ABA and cold stress in leaves. The specific tissue expression of some gene members indicated the relevant role of some ABA signalling genes in plant development. Moreover, their differential expression under ABA treatment or cold stress revealed those ABA signalling genes that responded to ABA, and those that were up- or down-regulated in response to cold stress. A reduced number of genes responded to both treatments. Specific PYL-PP2C-SnRK2 genes that had potential roles in germination were also detected, including those regulated early during the imbibition phase, those regulated later during the embryo extension and radicle emergence phase, and those induced or repressed during the whole germination process. CONCLUSIONS: The outcomes of this research open new research lines for agriculture and for assessing gene function in future studies.

Depression recurrence is accompanied by longer periods in default mode and more frequent attentional and reward processing dynamic brain-states during resting-state activity.

Recurrence in major depressive disorder (MDD) is common, but neurobiological models capturing vulnerability for recurrences are scarce. Disturbances in multiple resting-state networks have been linked to MDD, but most approaches focus on stable (vs. dynamic) network characteristics. We investigated how the brain's dynamical repertoire changes after patients transition from remission to recurrence of a new depressive episode. Sixty two drug-free, MDD-patients with ≥2 episodes underwent a baseline resting-state fMRI scan when in remission. Over 30-months follow-up, 11 patients with a recurrence and 17 matched-remitted MDD-patients without a recurrence underwent a second fMRI scan. Recurrent patterns of functional connectivity were characterized by applying Leading Eigenvector Dynamics Analysis (LEiDA). Differences between baseline and follow-up were identified for the 11 non-remitted patients, while data from the 17 matched-remitted patients was used as a validation dataset. After the transition into a depressive state, basal ganglia-anterior cingulate cortex (ACC) and visuo-attentional networks were detected significantly more often, whereas default mode network activity was found to have a longer duration. Additionally, the fMRI signal in the basal ganglia-ACC areas underlying the reward network, were significantly less synchronized with the rest of the brain after recurrence (compared to a state of remission). No significant changes were observed in the matched-remitted patients who were scanned twice while in remission. These findings characterize changes that may be associated with the transition from remission to recurrence and provide initial evidence of altered dynamical exploration of the brain's repertoire of functional networks when a recurrent depressive episode occurs.

COVID-19: gynecologic cancer surgery at a single center in Madrid.

OBJECTIVES: While numerous medical facilities have been forced to suspend oncological surgery due to system overload, debate has emerged on using non-surgical options on cancer cases during the pandemic. The goal of our study was to analyze, in a retrospective cohort study, the results of gynecological cancer surgery and evaluate postoperative complications in a single center in one of the most affected areas in Europe. METHODS: We retrospectively analyzed the records of patients who were referred between March 2020 and May 2020 for primary surgical treatment of breast, endometrial, ovarian, cervical, or vulvar cancer. RESULTS: The study included a total of 126 patients. Median age was 60 years (range 29-89). Patients were referred with breast (76/126, 60.3%), endometrial (29/126, 23%), ovarian (14/126, 11.1%), cervical (5/126, 4%), or vulvar cancer (2/126, 1.6%). Polymerase chain reaction (PCR) test for detection of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) was only conducted in 50% of cases due to the low availability of tests during the first phase of our study, and was indicated only in suspected cases according to the healthcare authorities' protocol. Median hospital stay was 1 day (range 0-18). Excluding breast surgery, laparoscopy was the most used procedure (43/126, 34.1%). 15 patients had a postoperative complication (15/126, 11.9%); only in 2 patients (2/15 13.3%) were there reports of Clavien-Dindo grade 3 or 4 complications. 6 patients tested positive for COVID-19 following a PCR diagnostic test, and these surgeries were cancelled. CONCLUSIONS: Adequate protective measures in the setting of COVID-19 free institutions enabled the continuity of cancer surgery without significant compromise of the safety of patients or healthcare workers.

Fertility preservation treatment of gynecological cancer patients in Spain: a national survey (GOFER study).

PURPOSE: To analyze the current management and use of fertility preservation (FP) treatments among different gynecologic oncology centers in Spain METHODS: From March to April 2019, a transversal study was conducted using a national online survey to consultants registered in the section of Gynecologic Oncology of the Spanish Society of Obstetrics and Gynecology. The survey contained 30 questions that assessed the perceptions and attitudes towards fertility-sparing strategies as well as its management in each participating center. RESULTS: A total of 51 responders from 12 out of 17 geographical regions of Spain answered the survey. According to 35 responders (68.63%), the age limit for offering FP was 40 years. In most of the centers, an ovarian reserve study is carried out prior to a FP procedure (34 responders, 66.67%). In cervical cancer size, limit for offering trachelectomy is 2 cm (40 responders, 78.43%), with LVSI as an exclusion factor for 26 (51%). Twenty-four (48.98%) responders reported that FP only in ovarian cancer stages IA, 12 (24.49%) also in stages IB, and an additional 13 (26.53%) up to stages IC. Most responders perform FP only in the absence of myometrial infiltration (30, 58.82%) in patients with g1-g2 endometrial cancer. CONCLUSIONS: The performance of professionals at the national level is uneven, demonstrating the need for referral centers to ensure optimal management. International guidelines should be more widely extended throughout Spain to homogenize the treatment of young oncology patients who wish to have children.

Emotional regulation for adolescents: a group-based treatment pilot study through the STEPPS programme.

BACKGROUND: Borderline personality disorder (BPD) usually begins in adolescence and manifests itself in adult life. Early intervention can improve the prognosis or reduce its severity. Nevertheless, there are currently few studies of adolescent patients with severe emotion instability and borderline personality traits. AIMS: To evaluate the effectiveness of the Systems Training for Emotional Predictability and Problem Solving (STEPPS) programme in a sample of 21 adolescents (aged 13-17 years) in the Child and Adolescents Mental Health Center of Tarragona in Spain. METHOD: We evaluated BPD traits using the Diagnostic Interview for Borderline Disorder-Revised (DIB-R) and the Global Clinical Impression Scale of Illness Severity for TLP (CGI-TLP). We compared pre- and post-treatment scores for the DIB-R, CGI-GI scale, general psychopathology using the Personality Inventory for Adolescents (PAI-A) and impulsivity with the Barratt Impulsivity Scale (BIS-11). The therapeutic objectives were evaluated with the Borderline Estimate Severity over Time (BEST) scale. RESULTS: There was a statistically significant improvement in the scores for the affective area and in the total score of the DIB-R, a decrease in the percentage of patients who failed to meet criteria for BPD, and an improvement (although not statistically significant) in the scores of the BEST scale throughout the treatment. The results of the CGI-GI scale showed global improvement in almost 72% of patients. CONCLUSION: Our study suggests that STEPPS can be an effective treatment to improve BPD symptoms and is very useful in community settings with limited resources in which efficient treatment alternatives must be sought. However, this conclusion must be interpreted with caution, as there is no comparison control group.

Genetic analysis of uterine aspirates improves the diagnostic value and captures the intra-tumor heterogeneity of endometrial cancers.

Endometrial cancer is the most common cancer of the female genital tract in developed countries. Although the majority of endometrial cancers are diagnosed at early stages and the 5-year overall survival is around 80%, early detection of these tumors is crucial to improve the survival of patients given that the advanced tumors are associated with a poor outcome. Furthermore, correct assessment of the pre-clinical diagnosis is decisive to guide the surgical treatment and management of the patient. In this sense, the potential of targeted genetic sequencing of uterine aspirates has been assessed as a pre-operative tool to obtain reliable information regarding the mutational profile of a given tumor, even in samples that are not histologically classifiable. A total of 83 paired samples were sequenced (uterine aspirates and hysterectomy specimens), including 62 endometrioid and non-endometrioid tumors, 10 cases of atypical hyperplasia and 11 non-cancerous endometrial disorders. Even though diagnosing endometrial cancer based exclusively on genetic alterations is currently unfeasible, mutations were mainly found in uterine aspirates from malignant disorders, suggesting its potential in the near future for supporting the standard histologic diagnosis. Moreover, this approach provides the first evidence of the high intra-tumor genetic heterogeneity associated with endometrial cancer, evident when multiple regions of tumors are analyzed from an individual hysterectomy. Notably, the genetic analysis of uterine aspirates captures this heterogeneity, solving the potential problem of incomplete genetic characterization when a single tumor biopsy is analyzed.

What Should We Expect After a Complete Cytoreduction at the Time of Interval or Primary Debulking Surgery in Advanced Ovarian Cancer?

PURPOSE: To compare the impact, in terms of survival, of complete cytoreduction after primary debulking surgery (PDS) and interval debulking surgery (IDS) in patients with advanced ovarian cancer (International Federation of Gynecology and Obstetrics stages III-IV) by reviewing the recent literature. METHODS: A search of the PubMed database during the last 7 years (2008-2014) was carried out looking for studies specifically showing data on median survival or disease-free survival after complete cytoreduction after either PDS or IDS. RESULTS: We found 24 publications including 14,182 patients with stages III to IV ovarian cancer. A total of 11871 patients (83.7 %) underwent PDS and 2311 (16.3 %) underwent interval debulking after neoadjuvant chemotherapy. A total of 4684 patients (33 %) were considered completely resected with microscopic residual disease. After PDS, the weighted average of median overall and progression-free survival was 43 and 17 months, respectively, for the whole group. After IDS, median and progression-free survival were 33 and 14 months. The rate of complete cytoreduction after PDS was inferior to the obtained in patients with IDS (27 vs. 59 %). However, the median survival in patients with complete cytoreduction with primary cytoreduction was 23 months longer than in the group with interval debulking (69 vs. 45 months). CONCLUSIONS: Complete cytoreduction after IDS yields a inferior outcome in terms of median survival than PDS of almost 2 years. Despite the higher rate of complete resection, IDS apparently fails to improve the results obtained by primary debulking.

Minimal Macroscopic Residual Disease (0.1-1 cm). Is It Still a Surgical Goal in Advanced Ovarian Cancer?

OBJECTIVE: The objective of this review was to try to determine by searching in the literature what is the survival in patients with advanced ovarian cancer after a primary debulking with minimal macroscopic residual disease (MMRD; 0.1-10 mm). Additionally, this review aimed to explore the survival in patients with residual disease from 0.1 to 0.5 cm. METHODS: A retrospective search was accomplished in the PubMed database looking for all English-language articles published between January 1, 2007 and December 31, 2014, under the following search strategy: "ovarian cancer and cytoreduction" or "ovarian cancer and phase III trial". We selected those articles that contain information on both percentage of MMRD (0.1-1 cm) and median overall survival (OS) in this subset of patients with stage III to stage IV ovarian cancer after primary debulking surgery. RESULTS: Thirteen publications were obtained including information of a total 11,999 patients with stage III to stage IV ovarian cancer. Five thousand thirty-seven patients (42%) had MMRD after the primary debulking (0.1-1 cm). Median overall survival in patients with MMRD was 40 months and disease-free survival (DFS) was 16 months. This group of patients obtained an advantage of 10 months in OS (40 vs 30 m) and 4 months in DFS (16 vs 12 m) compared with the group with suboptimal debulking (P < 0.001). Compared with the group of complete resection, patients with minimal macroscopic residuum showed a significant inferior median OS and DFS of 30 months and 14 months, respectively (OS, 70 vs 40 m; DFS, 30 vs 16 m) (P < 0.001). The group of residual disease of 0.1 to 0.5 cm reached a median survival of 53 months. CONCLUSIONS: Patients with ovarian cancer with MMRD after primary surgery obtain a modest but significant advantage in survival (10 months) over suboptimal patients. Patients with macroscopic residual disease (0.1-0.5 cm) obtain a better survival (53 months) than those with more than 0.5 to 1 cm. We propose that they should be classified as a different prognostic group.

A mutation in the brassinosteroid biosynthesis gene CpDWF5 disrupts vegetative and reproductive development and the salt stress response in squash (Cucurbita pepo).

A Cucurbita pepo mutant with multiple defects in growth and development has been identified and characterized. The mutant dwfcp displayed a dwarf phenotype with dark green and shrinking leaves, shortened internodes and petioles, shorter but thicker roots and greater root biomass, and reduced fertility. The causal mutation of the phenotype was found to disrupt gene Cp4.1LG17g04540, the squash orthologue of the Arabidopsis brassinosteroid (BR) biosynthesis gene DWF5, encoding for 7-dehydrocholesterol reductase. A single nucleotide transition (G > A) causes a splicing defect in intron 6 that leads to a premature stop codon and a truncated CpDWF5 protein. The mutation co-segregated with the dwarf phenotype in a large BC1S1 segregating population. The reduced expression of CpDWF5 and brassinolide (BL) content in most mutant organs, and partial rescue of the mutant phenotype by exogenous application of BL, showed that the primary cause of the dwarfism in dwfcp is a BR deficiency. The results showed that in C. pepo, CpDWF5 is not only a positive growth regulator of different plant organs but also a negative regulator of salt tolerance. During germination and the early stages of seedling development, the dwarf mutant was less affected by salt stress than the wild type, concomitantly with a greater upregulation of genes associated with salt tolerance, including those involved in abscisic acid (ABA) biosynthesis, ABA and Ca2+ signaling, and those coding for cation exchangers and transporters.

Toward stability of dynamic FC estimates in neuroimaging and electrophysiology: Solutions and limits.

Time-varying functional connectivity (FC) methods are used to map the spatiotemporal organization of brain activity. However, their estimation can be unstable, in the sense that different runs of the inference may yield different solutions. But to draw meaningful relations to behavior, estimates must be robust and reproducible. Here, we propose two solutions using the hidden Markov model (HMM) as a descriptive model of time-varying FC. The first, best ranked HMM, involves running the inference multiple times and selecting the best model based on a quantitative measure combining fitness and model complexity. The second, hierarchical-clustered HMM, generates stable cluster state time series by applying hierarchical clustering to the state time series obtained from multiple runs. Experimental results on fMRI and magnetoencephalography data demonstrate that these approaches substantially improve the stability of time-varying FC estimations. Overall, hierarchical-clustered HMM is preferred when the inference variability is high, while the best ranked HMM performs better otherwise.

Physiological and metabolomic responses of the ethylene insensitive squash mutant etr2b to drought.

The squash gain-of-function mutant etr2b disrupts the ethylene-binding domain of ethylene receptor CpETR2B, conferring partial ethylene insensitivity, changes in flower and fruit development, and enhanced salt tolerance. In this paper, we found that etr2b also confers a growth advantage as well as a physiological and metabolomic response that make the mutant better adapted to drought. Mutant plants had a higher root and leaf biomass than WT under both well-watered and drought conditions, but the reduction in growth parameters in response to drought was similar in WT and etr2b. Water deficit reduced all gas-exchange parameters in both WT and etr2b, but under moderate drought the mutant increased photosynthesis rate in comparison with control conditions, and showed a higher leaf CO2 concentration, transpiration rate, and stomata conductance than WT. The response of etr2b to drought indicates that ethylene is a negative regulator of plant growth under both control and drought. Since etr2b increased ABA content in well-watered plant, but prevented the induction of ABA production in response to drought, it is likely that the etr2b response under drought is not mediated by ABA. A 1H NMR metabolomic analysis revealed that etr2b enhances the accumulation of osmolytes (soluble sugars and trigonelline), unsaturated and polyunsaturated fatty acids, and phenolic compounds under drought, concomitantly with a reduction of malic- and fumaric-acid. The role of CpETR2B and ethylene in the regulation of these drought-protective metabolites is discussed.

Hysteroscopic surgery for conservative management in endometrial cancer: a review of the literature.

Endometrial cancer is the most common gynaecologic malignancy, usually diagnosed in postmenopausal women. However, an incidence rate of 2-14% of cases consisting of women under the age of 45 years old has been reported. Multiple reports have described the conservative treatment of this tumour in selected patients with the objective of preserving fertility. In this article, we review the literature to evaluate the results of conservative treatment of endometrial cancer with hysteroscopic resection.

Bevacizumab as front-line treatment for newly diagnosed epithelial cancer.

Ovarian cancer is the leading cause of death due to gynecological tumors. Despite the progress made during the last two decades in the surgery and chemotherapy of ovarian cancer, more than 70% of patients with advanced ovarian cancer will recur and die. Improvements in this field are coming from a better knowledge of the biology and the development of new-targeted agents. Bevacizumab, is a monoclonal antibody against VEGF that has shown activity as a monotherapy in recurrent ovarian cancer. The addition of bevacizumab to the front-line therapy of ovarian cancer has produced a benefit in progression-free survival in two randomized Phase III trials. This benefit seems to be greater in patients with more advanced disease. However, several questions remain to be clarified in the future, specially the optimal patient selection based on predictive biomarkers and the duration of therapy. Nevertheless, for the first time, the addition of a biologically targeted agent has shown an improvement in progression-free survival in the front-line treatment of advanced ovarian cancer and it is a proof of concept of the potential value of antiangiogenic therapy in ovarian cancer.